UC San Diego Receives $14M to Drive Precision Nutrition with Gut Microbiome Data – Center for Microbiome Innovation

A student processes microbiome samples in the UC San Diego School of Medicine lab of Rob Knight, PhD. Photo credit: Erik Jepsen/UC San Diego

The National Institutes of Health (NIH)s All of Us Research Program is a national effort to build a large, diverse database of 1 million or more people whom researchers can use to study health and disease.

The NIH is now awarding $170 million in grant funding to centers across the country to create a new consortium known as Nutrition for Precision Health, powered by the All of Us Research Program. The consortium will recruit a diverse pool of 10,000 All of Us Research Program participants to develop algorithms to predict individual responses to food and inform more personalized nutrition recommendations.

The Nutrition for Precision Health consortium includes $14.55 million to launch a new Microbiome and Metagenomics Center at UC San Diego. The center will analyze the microbiomes communities of microbes and their genetic material found in the stool samples of nutrition study participants.

A current challenge in precision nutrition is the inability to combine the many factors that affect how individuals respond to diet into a personalized nutrition regimen. These potential factors include the microbiome, metabolism, nutritional status, genetics and the environment. The way these factors interact to affect health is still poorly understood.

The Microbiome and Metagenomics Center at UC San Diego will help address some of these gaps.

Our new center will deploy more than a decade of research and development for the NIHs most exciting exploration yet, combining our understanding of the microbiome and human genetics with our groundbreaking technical and informatics advances to rapidly explore next-generation disease treatments based on precision nutrition, said Microbiome and Metagenomics Center co-leader Jack Gilbert, PhD, professor at UC San Diego School of Medicine and Scripps Institution of Oceanography.

The Microbiome and Metagenomics Center will be led by Gilbert and Rob Knight, PhD, along with co-investigators Andrew Bartko, PhD; Rebecca Fielding-Miller, PhD, MSPH; Kathleen Fisch, PhD; Maryam Gholami, PhD; David Gonzalez, PhD; Kristen Jepsen, PhD; Daniel McDonald, PhD; Camille Nebeker, EdD, MS; Pavel Pevzner, PhD; and Karsten Zengler, PhD, all at UC San Diego. The team will also collaborate closely with researchers at Duke University.

The center will build on what we have learned in other large-scale activities, including the Human Microbiome Project, the Earth Microbiome Project and the American Gut Project. It leverages many of the faculty and strengths brought together in the Center for Microbiome Innovation, as well as the cross-disciplinary microbiome community we have built here at UC San Diego, said Knight, professor and director of the Center for Microbiome Innovation at UC San Diego School of Medicine and Jacobs School of Engineering.

Bringing this expertise and technology to bear on the incredibly challenging problem of nutrition and health will enable a whole new level of precision in answering the age-old question of what should I eat today? We are just starting to understand how the microbiome can answer this with a surprising level of individual detail, not just broad-strokes generalizations for the whole population.

Nutrition for Precision Health will collect new microbiome and metagenomics data, along with other potentially predictive factors, and combine it with existing data in the All of Us database to develop a more complete picture of how individuals respond to different foods or dietary routines. The data will be integrated into the All of Us Researcher Workbench and made widely available, providing greater opportunities for researchers to make discoveries that could improve health and prevent or treat diseases and conditions affected by nutrition.

We know that nutrition, just like medicine, isnt one-size-fits-all, said Holly Nicastro, PhD, MPH, a coordinator of Nutrition for Precision Health at NIH. Nutrition for Precision Health will take into account an individuals genetics, gut microbes and other lifestyle, biological, environmental or social factors to help each individual develop eating recommendations that improve overall health.

All of Us opened for enrollment in 2018 and UC San Diego Health co-leads the programs implementation in California, where more than 37,000 people have already signed up to participate. To learn more about the All of Us Research Program and how to join, please visit JoinAllofUs.org.

The Microbiome and Metagenomics Center at UC San Diego is supported by the NIH Common Funds Nutrition for Precision Health, powered by the All of Us Research Program grant 1 U24 DK131617-01. Nutrition for Precision Health, powered by All of Us Research Program, and All of Us are service marks of the U.S. Department of Health and Human Services (HHS).

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UC San Diego Receives $14M to Drive Precision Nutrition with Gut Microbiome Data - Center for Microbiome Innovation

Balancing openness with Indigenous data sovereignty: An opportunity to leave no one behind in the journey to sequence all of life – pnas.org

Abstract

The field of genomics has benefited greatly from its openness approach to data sharing. However, with the increasing volume of sequence information being created and stored and the growing number of international genomics efforts, the equity of openness is under question. The United Nations Convention of Biodiversity aims to develop and adopt a standard policy on access and benefit-sharing for sequence information across signatory parties. This standardization will have profound implications on genomics research, requiring a new definition of open data sharing. The redefinition of openness is not unwarranted, as its limitations have unintentionally introduced barriers of engagement to some, including Indigenous Peoples. This commentary provides an insight into the key challenges of openness faced by the researchers who aspire to protect and conserve global biodiversity, including Indigenous flora and fauna, and presents immediate, practical solutions that, if implemented, will equip the genomics community with both the diversity and inclusivity required to respectfully protect global biodiversity.

Since the early days of the Bermuda Accord (1), Human Genome Project (2), and the Fort Lauderdale Agreement (3), the field of genomics has been strongly committed to open data sharing, and the calls for improved data-sharing approaches have only become even louder in the recent response to the COVID-19 outbreak (4). Rapid sequencing and open release of SARS-CoV-2 viral genome sequences throughout the outbreak have aided vaccine development, efficacy assessments, and continual monitoring of the viruss evolution in ways unimaginable a few decades ago (5). Similarly, the open release of the human reference genome and follow-up studies, such as the 1000 Genomes and the gnomAD data resource, have transformed our understanding of human genomic variation and disease and are exemplars of successful community resource-building projects. Now, new projects, such as the Earth BioGenome Project (6), aim to sequence the genomes of all living eukaryotic species to further understand molecular evolution, catalog the worlds biodiversity, and inform future conservation efforts. Such projects have the potential to bring the benefits of genomics to all people and species, but the past model of large consortia generating vast troves of data, favoring the inclusion of some over the exclusion of others, is both damaging and inequitable, requiring movement beyond the principles defined in Bermuda and updated in Toronto (7). These ambitious projects will require contributions from community and academic partners around the globe, and so the genomics community must develop and implement inclusive data-sharing policies and infrastructure that respect the rights and interests of all people.

Unfettered openness of genomic data, and the hows and whys of its enforcing open-science norms, impinge on the rights of Indigenous Peoples. As one example, the Navajo Nation became rightfully wary of freely contributing samples and genomic data and, in 2002, placed a tribal-wide Banishment Order on genetics research (8). In Canada, the three councils that fund research have formally adopted policies that were developed by Indigenous Peoples and scholars, which include that data and samples from Indigenous communities must be collected, analyzed, and disseminated under the terms of a mutually determined research agreement that respects community preferences to maintain control over, and access to, data and human biological materials collected for research (9). Only by reconsidering the definition of openness and who it benefits within the context of the current inequitable infrastructures can a more inclusive genomics community be built to responsibly sequence all of life for the future of life (6).

The prospect of cataloging the genome reference sequences for a huge number of representative species is only possible thanks to the exponential technological advances of the genomics community over the past 40 y. Whereas the initial Human Genome Project cost several billion in todays dollars (USD), the sequencing and assembly of high-quality vertebrate reference genomes now costs under $10,000 and continues to drop rapidly. Leveraging these new sequencing technologies, the Vertebrate Genomes Project has now generated over 100 new vertebrate reference genomes (10), and in the coming year, the Human Pangenome Reference Consortium (https://humanpangenome.org/) aims to create hundreds of new reference genomes that will better represent human genetic diversity. Along with reductions in sequencing costs, the underlying technologies are also becoming increasingly portable, with nanopore-based technologies now enabling on-site sequencing in the most remote corners of the world (11).

This genomics revolution is timely, in the midst of the Earths sixth mass extinction with 35,500 species on the International Union for Conservation of Nature Red (threatened) List (https://www.iucnredlist.org/en). Unlike the mass extinctions of the past, the sixth has been caused as a result of the actions of just one species, humans, and as a species we must act swiftly to halt the dangerous loss of biodiversity and extensively catalog what remains. Providing a catalog of genomic sequences for all life will be important for informing decisions about the effects of climate change on species diversity (12), the development of conservation strategies for threatened and endangered flora and fauna (13), assessing the success of ongoing conservation efforts, and for the preservation of genomic biodiversity before it is lost forever to extinction (6).

The importance of conserving biodiversity is universally recognized, but Earths biodiversity is not uniformly distributed. The Critical Ecosystem Partnership Fund currently recognizes 36 biodiversity hotspots, defined as regions with over 1,500 endemic vascular plant species. These hotspots have suffered a 70% loss of their native vegetation (14). Hotspots will be a top priority for any genomic conservation project, but many of these hotspots overlap Indigenous lands. Indigenous Peoples and lands historically have been exploited and excluded, and not engaged by the genomics community (15). Thus, it is imperative for the genomics community to work as equal partners with Indigenous Peoples going forward. To move forward, however, new infrastructure and policies are required to facilitate alternative modes of data sharing that can coexist with the current open-sharing policies of international genomics consortia. Current blanket open data-sharing policies override the rights of Indigenous Peoples, specifically the right to determine the use and mode of sharing Indigenous resources, which includes data. A fact that contravenes the United Nations (UN) Convention on Biological Diversity (CBD) as a matter of international law (16), violates several rights stipulated in the UN Declaration on the Rights of Indigenous Peoples (17), and results in perpetuating the marginalization of these Indigenous Peoples (18).

Open genomic data are defined here as genomic sequence information that is made freely available without restrictions on use, copying, or distribution. The worlds most popular molecular sequence databasessuch as the National Center for Biotechnology Informations GenBank, the European Nucleotide Archive, and DNA Database of Japanstrictly adhere to this model. Furthermore, in 2011 a Joint Data Archive Policy was drafted and adopted by many leading journals that reinforced open data sharing (19). Open data sharing in genomics has fostered a productive and collaborative international research community; it aspires to reduce systematic wealth and power inequalities by extending research opportunities from partners with a large investment in genomics capacity and capability to those partners with lower investment. In addition, open data sharing has provided knowledge that is more transparent, accessible, and verifiable, which has improved the efficiency and reliability of genomic research (20). However, despite its success, by negating local and regional representation and participation in governance, it has also resulted in the development of data-sharing policies that do not maximize opportunities for all participants in an equitable manner (21).

Moreover, when strictly mandated, open data policies can have the unintended consequence of excluding many minority communities, including those Indigenous Peoples who wish, for a variety of legitimate reasons, to retain control over the resources and data derived from their lands, species, and waters. The lack of clear, respectful, and operational policy that respects Indigenous rights breeds mistrust among Indigenous partners and not only hinders the inclusion of Indigenous science in international biodiversity and conservation efforts, but can also build opposition that results in the stagnation and reversal of Indigenous genomics projects (22). By demanding rigid policies on data sharing, the genomics community has forged rules premised on a single worldview. It undermines the rights and interests associated with traditional knowledge, a phenomenon scholars of Indigenous communities call epistemicide (23). Despite international consortia recognizing the rights of Indigenous Peoples, a lack of accountability and clarity for implementation of appropriate policies has exacerbated tensions between Indigenous communities and international genomic efforts (21).

In the past, the worlds of genomic science and Indigenous communities intersected mainly through Indigenous Peoples being used as subjects of research conducted by non-Indigenous researchers. Research was done on Indigenous Peoples, not by them and very rarely for them. The mistrust of the scientific community among Indigenous communities is well-earned: it has been caused by years of exploitation, mistrust, power imbalances, and inequality (24). It has included decades of taking and using Indigenous samples and data without adequate consent and consultation (24, 25); Indigenous data and samples not being properly attributed or acknowledged as coming from Indigenous lands and waters; Indigenous data being misused through bioprospecting and biopiracy (2628); Indigenous data being scientifically interpreted without cultural or contextual knowledge (29); and researchers who have claimed authority over the Indigenous world by relying on quantitative data rather than traditional knowledge and lived experience (30). Furthermore, the failure of researchers to disseminate research outcomes respectfully through mechanisms that are meaningful and applicable to Indigenous partners, such as asset-based approaches (31), has fomented a sense of a lack of control, lack of access, lack of opportunities to derive benefits from the use of traditional knowledge and genetic resources, and a lack of opportunity to integrate traditional ways of knowing into research plans (32). Through asset-based approaches, results can be communicated more meaningfully and ameliorate the five Ds of statistical data on Indigenous Peoples: disparity, deprivation, disadvantage, dysfunction, and difference (33).

Indigenous Peoples are the guardians and sovereign authorities of their lands and have been since time immemorial. Indigenous Peoples have their own unique beliefs, values, and worldviews. They are highly diverse; however, a commonality shared among many is a deep interconnectedness, interdependence, and intimate connection to their lands and waters (34). In regions of Africa, for example, life is not perceived through an individualistic lens but is experienced as relational and collective; this worldview is known as Ubuntu (35), an example of Indigenous or traditional knowledge that is based upon lived experience extending as far back as the Pleistocene era (36). It has been developed over time, informed by an extensive system of principles, beliefs, and traditions. In New Zealand, a governmental inquiry into the Mori knowledge system, or Mtauranga Mori, concluded that this system of knowledge is fundamentally different from Western science. The Mori knowledge framework has evolved through its own cultural context and evolutionary pathway (37). These epistemological differences in knowledge sharing and individual possession are largely incommensurate with existing intellectual property rights, which privilege and support Eurocentric notions of knowledge commons with no or limited rules around access to knowledge and property. However, rather than being treated as outdated or inferiorattitudes that embody cognitive imperialism and epistemic violencetraditional knowledge systems should be acknowledged, integrated, treated as a coequal, and considered when interpreting findings. One system of knowledge should not eclipse the other. When recognized in this way, traditional knowledge is integral to knowledge production contributing both technically and scientifically to the protection and sustainable development of Indigenous lands, resources, and data through an intrinsic understanding of the interdependence of land and its inhabitants (38).

Any complete catalog of Earths biodiversity must necessarily include species on the lands of Indigenous Peoples. Thus, for global genomic conservation efforts to succeed, the genomics community will need to adapt its open data policies to Indigenous data sovereignty and knowledge systems. To achieve this, policies must be operationalized that embrace multiparadigmatic research approaches (39, 40) that recognize the inherent sovereignty of Indigenous Peoples and that remove barriers to those Indigenous communities who wish to contribute to bioconservation as equal partners.

Over the past two decades there has been an international call for the recognition and protection of Indigenous data rights. Indigenous data sovereignty (IDSov) refers to the individual and collective rights of Indigenous Peoples to control data from and about their communities, land, species, and waters (30).

In 2010, the Nagoya Protocol was established and adopted by the UN CBD (41) to protect, promote, and fulfill this right. It has been fundamental in providing guidance on access and benefit-sharing of Indigenous resources and data. Article 12 states that parties shall, in accordance with domestic law, take into consideration Indigenous and local communities customary laws, community protocols, and procedures. The Nagoya Protocol now has 2,000 internationally recognized certificates of compliance, but notably does not include some nations that have both Indigenous Peoples and a large genomic research program (e.g., the United States, Canada, New Zealand, and Australia). Despite this, domestic legislation over a sample/genetic resource from a signatory nation extends to where that sample/genetic resource is housed or used. Thus, nonsignatory countries are expected to implement Nagoya legislation if resources have been obtained from a country where the Nagoya Protocol is enforced.

In 2014, the UNs General Assembly adopted the United Nations Declaration on the Rights of Indigenous Peoples (17), which affirms the right of Indigenous Peoples to control, protect, and develop manifestations of their sciences, technologies, and cultures, including human and genetic resources (Article 31), the right to the conservation and protection of the environment and the productive capacity of their lands (Article 29), as well as the right to participate in decision-making in matters which would affect their rights (Article 18). Furthermore, the UN has also developed 17 Sustainable Development Goals (SDG) to be achieved by 2030. In 2015, these were agreed upon and adopted by 193 countries worldwide, including the United States, Canada, New Zealand, and Australia (42). SDG 15 aims to Protect, restore and promote sustainable use of terrestrial ecosystems, sustainably manage forests, combat desertification, and halt and reverse land degradation and halt biodiversity loss (42). Its associated Sustainable Development Solutions Network Target 15.6 aims to ensure fair and equitable sharing of the benefits arising from the utilization of genetic resources, and promote appropriate access to genetic resources (42), a provision that has particular importance for marginalized communities, including Indigenous Peoples. Additionally, many individual nations have binding legislation covering their own Indigenous populations. For example, in New Zealand, the founding charter, subsequent legislation, and other policies covering Indigenous species require that all data and intellectual property be retained by the government within New Zealand (43, 44). Indigenous claims to cultural and intellectual property are also being addressed in New Zealand, where a work program to address the issues identified in WAI262 Report Ko Aotearoa Tenei has just been developed and some projects have been initiated (45, 46).

Rights secured through IDSov can be at odds with the open by default culture of the genomics field, leaving Indigenous genomic data unsupported by the decades of open infrastructure that has been built by the genomics community. In an effort to close the gap, higher-income countries, such as Australia, Canada, and New Zealand, have established national Indigenous-driven human genomic efforts, including the work of the National Centre for Indigenous Genomics (https://ncig.anu.edu.au/), the Silent Genomes project, and the Aotearoa Variome, respectively (47). These national efforts are examples of Indigenous-driven human genomics research programs intended to directly benefit Indigenous Peoples. In Canada, protocols have also been established for the protection of nonhuman data, specifically through the Tri-Council Policy Statement (48) on research ethics that provides protection over Indigenous samples. Furthermore, research licensing in the three territories of Canada protects samples and data collected on Indigenous lands (4951).

To date, three national-level IDSov networks provide processes and protocols to enable Indigenous data governance (SI Appendix, Table S1): Te Mana Raraunga Mori Data Sovereignty Network, the United States Indigenous Data Sovereignty Network, and the Maiam nayri Wingara Aboriginal and Torres Strait Islander Data Sovereignty Group in Australia. However, blanket adoption of national efforts is not feasible in countries that lack substantial genomics investment or in which Indigenous governance structures are less established or respected.

Alongside the national efforts, IDSov is also gaining recognition on an international level through a variety of initiatives. For example, in 2019 the Global Indigenous Data Alliance (GIDA) (https://www.gida-global.org) was established to build a global community for the development of data-sharing infrastructure, data-driven research, and data use policies. In 2020, ENRICH (Equity in Indigenous Research and Innovation Co-ordinating Hub) was established in a collaboration between New York University and the University of Waikato. ENRICH supports IDSov-based protocols, Indigenous-centered standard-setting mechanisms, and machine-focused technology that informs policy and transforms institutional and research practices (https://www.enrich-hub.org/bc-labels). Platforms such as the International IDSov Interest Group have also been set up under the Research Data Alliance (https://www.rd-alliance.org/groups/international-indigenous-data-sovereignty-ig). These initiatives include the development of specific tools and practical mechanisms alongside education and training to provide a foundation for further development of ethical research guidelines that address Indigenous rights and interests.

The FAIR principles are a common refrain of open data efforts that encourage data to be Findable, Accessible, Interoperable, and Reusable (52). In 2019, GIDA released a set of complementary CARE' Principles (53) that highlight the core values and expectations of Indigenous Peoples when engaging with the scientific community. These principles encourage the consideration of collective benefit, authority to control, responsibility, and ethics in Indigenous data governance. Such efforts toward developing new policies to respect and promote IDSov are essential; however, there is now the difficult challenge of informing and implementing IDSov principles, policy, and mechanisms within the global field of genomics (54).

A brief inspection of the publicly available data access and governance policies of international genomics-based consortia showcases where progress has been made and where it is needed the most. Notable exceptions include the H3Africa Consortium (55), which has led the way in the adoption of Indigenous policies for human genomics, providing clarity to researchers through an in-depth set of principles and guidelines that hold participating researchers accountable for their implementation. At present, many nonhuman-focused consortia lack governance and data policy information. Some claim to recognize the rights of Indigenous Peoples but provide no pragmatic implementation plan or accountability measures. Exceptions in the nonhuman space include Genomics Aotearoa (56), which have actively developed engagement and biobanking frameworks in partnership with Mori to guide all consortium members while engaging with Indigenous data. However, for many other efforts, the lack of clear and transparent adoption of IDSov policy is problematic for a successful engagement between genomic researchers and Indigenous partners, given the incompatibility of unfettered open data and IDSov. Moreover, there remain ongoing practical challenges in keeping provenance and cultural connections between Indigenous communities and the data generated from their lands and waters transparent and clear within the databases themselves. Open data have successfully encouraged transparency and inclusion among international genomic research collaborations, but it is now time to ensure such success extends to including Indigenous partners and IDSov in these collaborative infrastructures.

The conflicts between IDSov and open data in genomics research are not new and have been extensively discussed (18). Progress, although slow, is being made to identify and provide solutions to these incompatibilities. Local Contexts is a key international initiative that recognizes and advances the rights of Indigenous Peoples in museum collections and their data through a unique set of traditional knowledge and biocultural labels and notices (with licenses under development) (57). Inspired by the Creative Commons licensing structure (https://creativecommons.org/), Local Contexts initiated this work in 2010, producing a suite of practical mechanisms designed to enhance the protection of Indigenous communities and hold researchers accountable. That process entailed community partnership and collaboration, as will scientific projects that follow its precepts. As durable digital tags with unique IDs, the labels (for communities) and the notices (58) (for researchers and institutions) provide an opportunity to include Indigenous protocols and expectations around the sharing of knowledge as metadata within the data infrastructures. As a result, this information, such as the origin of samples and data, travels with the data across platforms. Through this mechanism, Indigenous partners are given a voice, and future research engagement is encouraged; its aspiration is to leave no one behind.

The field of genomics is operating under data-sharing practices established decades ago. A status quo that began with the Bermuda Principles defining the best mode of data sharing with respect to human data, these principles were then extended by the Fort Lauderdale Agreement to include nonhuman data and further updated in Toronto (59). Since Toronto, community-based efforts such as the Global Alliance for Genomics and Health (https://www.ga4gh.org) have reconsidered these data-sharing frameworks, developing responsible and inclusive human data-sharing policies and toolkits for genomics researchers.

An equal effort is now needed for nonhuman data, and nonhuman genomics continues to embed inherent biases and inequality, doing little to address existing disparities. Indigenous Peoples are part of contemporary life, they are not outside of modernity. Indigenous voices need to be heard. It is both a moral responsibility and a legal obligation to share benefits of research fairly and to respect traditional knowledge derived from their lands and waters. Genomics research needs to implement a future that has hitherto been mainly aspirational, a future that builds intellectual bridges between different ways of knowing and being. The appropriate acknowledgment, understanding, and implementation of Indigenous Peoples rights while conducting genomic research provide a foundation to reach this goal.

Change must happen both at the individual and institutional level to ensure that Earths genomic biodiversity can be ethically cataloged. Several suggestions, references, and resources are provided to aid this transformation.

Operationalizing clear policies that respect Indigenous rights will communicate to potential Indigenous research partners what principles guide the research activity, the manner in which the researchers will conduct themselves, and the standards enforced and upheld. By providing clarity and increasing transparency, trust can be built and remove potential impediments to building relationships with Indigenous partners. When implementing these policies, inclusion does not equal assimilation. Respecting and cultivating divergent practices and beliefs is important to avoid monoculturalization. Indigenous Peoples wishes regarding data access and benefit-sharing must be honored, making one-size-fits-all open data licenses inappropriate. International consortia seeking to perform Indigenous research must implement IDSov policies and engage with Indigenous communities in a manner that allows them to contribute on mutually agreed terms.

To change the culture from research that is done to Indigenous Peoples rather than by or for them, researchers, institutes, scientific journals, repositories, and funding bodies must change the status quo. Researchers must reflect upon their personal assumptions and biases and listen attentively to alternative frameworks. This can be done through questioning scientific orthodoxies and recognizing that research, even when good is intended for all humanity, can create power and benefit imbalances. In beginning a new project, researchers must question the expectations of each research partner, the genomics community, the institutions, the funding bodies, the ethics review boards, the Indigenous partners, and the Indigenous communities who have provenance over the data and organisms in question. Rather than pushing the boundaries, attempt to foresee the consequences and deeply consider at the outset of each research project its social license and duty to diverse societies.

Although significant progress toward policy development has been made, further clarity is particularly needed for nonhuman Indigenous data. As species do not respect country or land borders, policy is required to provide clarity to researchers regarding species that straddle the borders of Indigenous and non-Indigenous lands, and those species that are of special importance to Indigenous Peoples but are found also on non-Indigenous lands.

To ensure an even distribution of power, financial resourcing, and benefit, researchers who wish to partner with Indigenous communities must first ensure their own cultural competency while also prioritizing engagement with Indigenous communities at the onset of the study. This allows the necessary time for a partner relationship to be built from mutual agreement as to the role and responsibilities of both groups, the community, and the researchers. Early engagement also provides Indigenous communities with relevant details pertaining to all aspects of the project, from sample collection to potential research publications and intellectual property development and benefit-sharing in a clear, transparent, and accessible fashion, including: the background, the scope of the research, potential outcomes of the project, and any foreseen risks associated with the research. By doing so, both researchers and Indigenous partners have all of the necessary information and education to conceptualize and design the research project in a concerted fashion that acknowledges the communities long-standing relationship with local species and greater breadth of knowledge of the ecological systems and how they are changing (60, 61). This equips all parties with a fair and equal voice in setting research goals, understanding and contextualizing data, and planning of the time and budgetary requirements needed to achieve research goals ethically. Early engagement also allows project outcomes to be jointly interpreted, drafted, and disseminated by multiple parties, rather than the typical one-sided reporting driven by research institutions. Furthermore, the dissemination of outcomes in the Indigenous local languages will enhance accessibility for Indigenous community partners so that the community can relay the outcomes to others, and this process does not depend on an external scientist. This joint dissemination of research outcomes is extremely important for maintaining trust, communicating mutual benefits, and ensuring that Indigenous knowledge is not misappropriated. Indigenous partners should also be included in the evaluation phases of a project to include Indigenous best practice and better understand research impacts in an Indigenous context.

Projects that have been conceptualized and funded prior to engagement already fall outside the best practices for engagement with Indigenous Peoples. Here, other considerations are crucial for a successful partnership, such as minimizing power inequalities throughout the remaining research period. Indigenous Peoples, such as the African San tribe, Mori in New Zealand, and the Australian Institute of Aboriginal and Torres Strait Islander Studies in Australia, have considered and documented the best practices and expectations for engagement in these circumstances (60, 62, 63). These best practices include understanding and incorporating the expectations of Indigenous communities into the research plan; clearly communicating the scope of research, timelines, funding, methods of consent as informed by the Indigenous research partners, and all potential research outcomes; identifying short- and long-term risks and benefits and how they will be shared; building sustainable long-term governance and communication frameworks; discussing potential barriers to project completion and the impacts of project incompletion on partners; and evaluating the cultural competency of the research team. A focus on the process rather than the product is also helpful in assuring that the project has an adequate timeframe and budget to achieve its stated outcomes in a respectful manner, keeping in mind that fast-paced, product-oriented, and extractive strategies are not compatible with Indigenous cultures and may lead to irrevocable harm (24).

The fully open model of sharing must be challenged; the inclusion of some should not be valued over the exclusion of others. Policies need to be cognizant of the history, needs, and worldviews distinct to each Indigenous community (64). To operationalize situated openness, a pragmatic implementation of IDSov policies and licenses is necessary. As it stands, IDSov policies are being actively developed and adopted; however, progress depends on implementing and enforcing these policies by the genomics research community. Ambitious international goals, such as the push to catalog all genomic information on Earth, sit at the interface of genomic science and Indigenous ways of knowing. Effective implementation of IDSov policies and power sharing between communities is necessary to ethically realize such visions. This will require multiparadigm research methodologies built upon commonalities, but also accepting of divergent beliefs and practices, to move away from the extractive and exploitative strategies of past research on Indigenous Peoples. The task is hard, but eminently achievable, as recently demonstrated by more inclusive, diverse, and political research paradigms developed by researchers in New Zealand, Australia, North America, Africa, Central and South America, and the Pacific (40). These stand as positive examples for how to best champion polycultural expression and establish a new status quo for the genomics community.

Open data sharing in genomics has fueled progress and brought benefits to a field that continues to grow, even as it ramifies into many different fields of research and application. However, it is evident that those doing the sharing, to date, have taken on very little riskand in many cases, stand to benefitfrom the act of openly sharing. To impose the same open data requirements on those with the most to lose by relinquishing control over use of resources and data is unfair, and when openness is stated as a prerequisite for participation, it can have the unintended effect of excluding marginalized communities. An infrastructure that allows for multiple modes of data sharing is needed, particularly modes that allow for materials and data over which Indigenous communities exert stewardship to remain under their control, and with respectful communication of findings and sharing of benefits with Indigenous communities. The Native BioData Consortium is the first tribal-driven BioBank in the United States (NBDC; https://nativebio.org/) and provides a model of how to facilitate the flexibility needed to share data in a manner respectful of all parties and worldviews. In an Aboriginal and Torres Strait Islander context, the idea of kinship speaks toward the interconnectedness and interdependence of all life (65), as well as water and geographical features. This relationship to land is shared among Mori (66), and First Nations and Inuit Peoples (67). Adequate time and resources must be assigned to directly coordinate conservation efforts with Indigenous partners who are the experts on implementing systems thinking approaches within their own lands.

To sequence everything requires the help and participation of everyone on equal and mutually agreed terms. Ultimately, genomic technologies can be advanced to the point of becoming commonplace, and initiatives are already under way to bring DNA sequencing into classrooms (68). As the field of genomics progresses, all research partners have the responsibility and opportunity to build a trustworthy and inclusive research community. Investing in outreach programs that pass on the latest technologies and methods such as the SING Consortium (https://www.singconsortium.org/) and IndigiData (https://indigidata.nativebio.org/) workshops, this capacity building will facilitate local research, fueled by local priorities and guided by local best practice. Graduate and undergraduate genomics courses should also include training in ethics and engagement best practices to improve the cultural competency of non-Indigenous researchers that may enter this space. This provides cultural safety but also alleviates expectations and responsibilities resting solely on Indigenous researchers shoulders (47). Infrastructure and opportunities for media producers local to the study should also be developed for the dissemination of genomic research findings in multiple languages, regions, and formats. These efforts will enable all partners, including Indigenous and other marginalized communities, to directly contribute to ongoing international genomics efforts and by fostering diversity within the field. It can help ensure that genomics infrastructure will be accessible and beneficial for all, and practices put in place to foster trust over the long haul.

Parties to the UN CBD and its Nagoya Protocol are currently reviewing the meaning of digital sequence information (DSI) and the requirement for a change to access and benefit-sharing policies under the convention that pertain to such DSI (41). As it stands, the term DSI is a placeholder used to facilitate discussions surrounding three data types: 1) DNA and RNA; 2) DNA, RNA nucleotide sequences, and protein-peptide amino acid sequences; and 3) DNA, RNA, and protein sequences as well as digital information pertaining to metabolites and macromolecules. All three of these definitions would include data contributing to reference genome sequences for nonhuman organisms. Prior to these discussions, there had been a fourth option for associated information, including traditional knowledge (69), but this was removed during the revision.

Despite the Nagoya Protocol calling for access and benefit-sharing, to date only 16 signatory countries have domestic legislation regarding DSI. Eighteen additional signatories are planning to or are in the process of drafting such legislation (70). The United States is not a signatory to the Convention, but United States representatives have attended the November 2021 review conference in China, and will attend further discussions in 2022. Many nations involved in the Earth BioGenome Project, European Reference Genome Atlas (https://vertebrategenomesproject.org/erga), the Human Pangenome Reference Consortium, and other international genomic collaborations are signatories. The ongoing CBD review has the goal of standardizing terms for access and benefit-sharing among all signatories, and discussions continue to include DSI. The international committee overseeing the CBD has expressed discontent with the status quo. Disparate policies among signatories and other major nations have led to the interpretation of open access to DSI as sufficient to fulfill access and benefit-sharing requirements in some cases, while in other cases formal agreements are required to share samples or sequence data. The review considers 13 recent publications relevant to access, benefit-sharing, and sequence data that have been categorized into five policy archetypes, some of which are mutually exclusive, while others can be combined (Table 1). Each archetype will be considered for cost-effectiveness, feasibility, and practicality, as well as uses of traditional knowledge. Access and benefit-sharing standards will be addressed again before a standardized policy is agreed upon and incorporated into the convention framework.

Potential policy options under review of the Convention on Biological Diversity, with respect to access and benefit-sharing and digital sequence information

The lack of infrastructure to trace the geographic origin of samples and DSI is readily apparent: only 12% of the sequence data in publicly available databases specifies a country of origin. The lack of proper infrastructure to monitor compliance with access, benefit-sharing, and sharing of DSI at each point in the value chain has also been flagged as a potential barrier to agreement, with block chain smart contracts highlighted as a potential solution (71).

Policies about access and benefit-sharing, and about sharing of DSI are in flux, but it is clear that unfettered open access to data and materials, including sharing of sequence data, is being questioned when it comes into conflict with Indigenous rights. National and international law are likely to evolve, and the scientific community would be wise to both directly engage in helping set the standards and practices but also to comply with the emerging laws, norms, and practices governed by national and international law.

Following basic principles in a transparent manner, with all parties having access to and an equal understanding of the research project, will help remove the barriers between the genomics community and Indigenous partners, and will facilitate a long-term partnership founded on trust, safety, honesty, and accountability. The genomics community must engage with each Indigenous partner in accordance with that communitys specific traditional beliefs, practices, and connections to the organisms being studied and the appropriate way to engage with other people in discussions of other organisms. As Chip Colwell, previous senior curator of anthropology at the Denver Museum of Nature and Science, stated during SING Aotearoa (https://www.singaotearoa.nz), Indigenous People are not anti-science [but] they demand a science that restores the dignity of Indigenous Peoples and is carried out with fundamental respect (72). This is now the responsibility of each researcher, consortium, journal, data repository, and funding body that seeks engagement with data or resources derived from Indigenous lands. Practical mechanisms like the traditional knowledge and biocultural labels and notices, and Indigenous-driven biobanks such as the Native BioData Consortium, provide proven models. The field has come a long way in working toward diversity, and the wind is at our back. Indigenous researchers have already put great effort into developing guidelines, best practices, legal and extralegal tools, and new research paradigms (SI Appendix, Table S1). Equipped with this knowledge, the community must now capitalize on the opportunity to build an inclusive, respectful, and mutually beneficial future for genomics.

There are no data underlying this work.

We thank Carla Easter (Education and Outreach Department of the National Human Genome Research Institute, NIH), Jenny Reardon (University of California, Santa Cruz), Harris Lewin (University of California, Davis), and Jacob S. Sherkow (University of Illinois) for their time in reviewing and consulting in preparation of this manuscript; and IndigiData and SING USA, Canada, and Aotearoa for their support and guidance throughout the manuscript-drafting process. This work was supported, in part, by the Intramural Research Program of the National Human Genome Research Institute, NIH (A.M.M.C. and A.M.P.). J.G. is funded by NIH Grant 5R01CA237118-02 and a Canadian Institutes of Health Research Fellowship (202012MFE-459170-174211). Development of the Biocultural Label Initiative has been supported by Catalyst Seeding funds for the project Te Tukiri o te Tonga: Recognizing Indigenous Interests in Genetic Resources provided by the New Zealand Ministry of Business, Innovation and Employment and administered by the Royal Society Te Aprangi (19UOW008CSG to M.L.H. and J.A.), leveraging the existing Local Contexts (https://localcontexts.org/) platform supported by the National Endowment for the Humanities (PR 234372-16 and PE 263553-19 to J.A.) and the Institute of Museums and Library Services in the United States (RE-246475-OLS-20 to J.A.), New York University Graduate School of Arts and Sciences, and the University of Waikato. Continuing infrastructure development is supported through the Equity for Indigenous Research and Innovation Co-ordinating Hub based at New York University and University of Waikato (https://www.enrich-hub.org/). The Biocultural Label Initiative is extended through use cases, supported and refined by the Aotearoa Biocultural Label Working Group, Federation of Mori Authorities Innovation (https://www.foma.org.nz/), Te Mana Rauranga (https://www.temanararaunga.maori.nz/), Genomics Aotearoa (https://www.genomics-aotearoa.org.nz/), Indigenous Design and Innovation Aotearoa (https://www.idia.nz/), the Genomics Observatories Metadatabase (https://geome-db.org/), the Ira Moana Genes of the Sea Project (https://sites.massey.ac.nz/iramoana/), supported by Catalyst Seeding funds provided by the New Zealand Ministry of Business, Innovation and Employment and administered by the Royal Society Te Aprangi, 17MAU309CSG to L.L.), and a Massey University Research Fund to L.L. L.L. is supported by a Rutherford Foundation Discovery Fellowship. J.G. and R.C.-D. are funded by the US National Cancer Institute through Grant R01 CA227118 (sulstonproject.org). M.Z.A. is funded by NIH Grant R01AI148788 and NSF CAREER 2046863.

Author contributions: A.M.M.C., J.A., L.L., M.L.H., M.Z.A., B.T., J.G., R.C.-D., and H.R.P. designed research; A.M.M.C. and A.M.P. wrote the paper; and J.A., L.L., M.L.H., M.Z.A., B.T., J.G., R.C.-D., and H.R.P. contributed to drafting text.

The authors declare no competing interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2115860119/-/DCSupplemental.

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Balancing openness with Indigenous data sovereignty: An opportunity to leave no one behind in the journey to sequence all of life - pnas.org

SwabSeq: Scalable, Sensitive and Fast COVID-19 Testing – UCLA Newsroom

After much of Los Angeles went dark in the spring of 2020 amid the growing SARS-CoV-2 threat, two UCLA scientists and their small teambegan working late nights on the fifth floor of the Gonda (Goldschmied) Neuroscience and Genetics Research Center, developing technology that would pave the way for the UCLA community to safely return to campus.

The safer-at-home orders had shut down all but the few core campus activities and services deemed essential. While that meant the suspension of most laboratory research, it didnt apply to a new project led by Valerie Arboleda M.D. 14,Ph.D. 14, assistant professor of pathology and human genetics, and Joshua Bloom 06, a research scientist in human genetics and an adjunct professor in computational biology. Through their collaboration with Octant Bio, a biotech company founded and incubated at UCLA; faculty in UCLAs departments of human genetics and computational medicine; UCLA Health; and other academic institutions across the country, their research ultimately found its way from the high-tech lab Arboleda and Bloom named SwabSeq to vending machines across campus.UCLA faculty, staff and students returning last fall were able to easily access the free COVID-19 test kits, with picking up a testas simple as grabbing a snack: Users simply register for the SwabSeq test by scanning a QR code with their smartphone, retrieve the kit and collect their saliva sample, then deposit the kit in a drop box next to the machine. An email or text notifies them when they can access a secure website for their result.

Diagnosing COVID-19 typically involves polymerase chain reaction (PCR) testing, but as a tool for mass screening of asymptomatic individuals, the approach is limited in its capacity. To run tens of thousands of tests simultaneously, SwabSeq harnesses the power of next-generation DNA sequencing a revolutionary technology thats come of age in the last 15 years and enables the processing of millions of DNA fragments at a time. The testing platform also bypasses a step typically required in the PCR method that of extracting RNA from samples, which can take days to process.

Im thrilled that SwabSeq helped put us back on campus and that my students and I are able to come into the lab.

Valerie Arboleda

SwabSeq attaches a piece of DNA that acts like a molecular barcode to each persons sample, enabling the labs scientists to combine large batches of samples in a genomic sequencing machine. Viewing the barcodes in the resulting sequence, the technology can quickly identify the samples that have the coronavirus that causes COVID-19. SwabSeq can return individual test results in about 24 hours, with highly accurate results the false-positive rate is just 0.2%.

Michal Czerwonka

Rachel Young, laboratory supervisor and clinical laboratory scientist for the COVID-19 SwabSeq lab

SwabSeq has now tested more than half a million specimens from UCLA, as well as from a handful of other universities in Southern California and from the Los Angeles Unified School District. A $13.3 million contract recently awarded by the National Institutes of Health sets the stage for an expansion of SwabSeqs efforts.

This is an innovative use of genomic sequencing for COVID-19 testing that is uniquely scalable to thousands of samples per day, [and that is] sensitive and fast a combination that is challenging to find in diagnostic testing, Arboleda says. Its not cost-effective as a test for a few people, or if you have someone in the hospital who needs an immediate result, but its very effective as a screening tool for large asymptomatic populations.

Neither Arboleda nor Bloom could have predicted they would one day find themselves leading a major element of UCLAs research response to a once-in-a-century pandemic.

Arboleda entered the David Geffen School of Medicine at UCLA intending to become a full-time clinician, but when she took a year off from her medical school studies to work in a lab, she found her true calling. She enrolled in the UCLA Medical Student Training Program, graduating in 2014 with both an M.D. and a Ph.D. in human genetics. As a faculty member, she now devotes about 80% of her time to research, with much of the focus on rare genetic syndromes.

Bloom, trained as a geneticist and a computational biologist, has used model systems such as yeast to develop experimental and computational methods for identifying the heritable genetic factors underlying gene expression differences and other complex traits in large populations. Ive worked on some really abstract problems. Diagnostic testing in a pandemic is definitely not something I thought Id ever be involved in, he says, smiling.

Michal Czerwonka

A machine in the SwabSeq laboratory

Like most of their UCLA colleagues and much of the rest of the world, Bloom and Arboleda saw their work routines upended by the pandemic. Bloom was grappling with the new reality when he received a call from Sri Kosuri, a UCLA assistant professor of chemistry and biochemistry and co-founder/CEO of Emeryville, California-based Octant Bio, the startup where Bloom was a consultant and where early pilot studies for SwabSeq were conducted.

He suggested we could turn the drug-screening technology Octant was using into a COVID test, and asked if I could help with the computational work, Bloom recalls. There were other people at UCLA who were also thinking that with all these smart people here, we should be able to develop a test. From there we began to have large group meetings involving multiple universities sharing information.

When Arboleda heard about the nascent project from a faculty colleague, she knew she could be helpful. In addition to the expertise in molecular biology she could apply to setting up the experiments, her training in pathology gave her the experience with regulatory matters that would need to be addressed once the test was developed. She agreed to collaborate with Bloom, who used his expertise in informatics to optimize the automated DNA sequencing process toward the goal of producing accurate diagnostic readouts.

The two spent a good part of April and May 2020 in the lab. We would do the assay and put it on the sequencer, then Josh would analyze it as soon as it came off the machine, Arboleda says. Based on that, the next day we would adjust a couple of parameters and rerun the experiment.

PreCOVID-19, she had become accustomed to a supervisory role as a principal investigator overseeing a team of scientists. I hadnt gone back to the lab in a while, she says. It was a wild two months, where I felt like a grad student again!

The number and pace of the iteration cycles a new one every 24 hours made this research project unlike any other Bloom had seen. The sequencing technology enables that, because you can tweak a bunch of things and get readouts for them all at once, he says.

But more than that, he credits the speed with which SwabSeq moved from concept to reality to an all-hands-on-deck approach befitting the urgency of the need. We had senior faculty, including department heads, engaged and excited to help, Bloom says.

One of those department heads isEleazar Eskin,chair of the Department of Computational Medicine,a departmentaffiliated with both UCLA Samueli School of Engineering and the medical school. He hascoordinatedlogistics and business operations to ensure that the lab operates efficiently and remainsflexibleenough toadapt to changing circumstances, such asthe appearance of theomicron variant of the virus.Eskinalso built the custom software for SwabSeq'slab-information management system.

Adds Arboleda: Everyone knew it was important and contributed in whatever way would support the mission, whether it was getting space, fundingor institutional review board approvals. And since only people who were doing COVID work could come to campus, I had people on my team who said, OK, Ill put on a mask and do whats needed.

Michal Czerwonka

Hard at work in the SwabSeq lab

The SwabSeq lab now occupies an entire floor in the Center for Health Sciences South Tower. The space is divided into three rooms, each dedicated to a portion of the test. One room is for handling samples; a second is used as a clean room and storage area; and a third, its walls lined with high-level sequencers, is for post-PCR sequencing. All over, freezers and refrigerators store enough reagents for millions of tests. The lab isnt necessarily a one-off Arboleda notes that the technology can be applied to general infectious disease testing and surveillance. Its flexible protocol can rapidly scale up testing and provide a solution to the need for population-wide testing to stem future pandemics, she says.

For now, aside from regular meetings to discuss SwabSeq development and high-level technical issues, the scientists have returned to the work they were doing before everything changed in March 2020. Im thrilled that SwabSeq helped put us back on campus and that my students and I are able to come into the lab, Arboleda says. Now if someone tests positive, no one worries because that person can stay home, and we know we can all easily get tested.

Continued here:

SwabSeq: Scalable, Sensitive and Fast COVID-19 Testing - UCLA Newsroom

Natural selection has been acting on hundreds of human genes in the last 3,000 years – Livescience.com

Natural selection, the evolutionary process that guides which traits become more common in a population, has been acting on us for the past 3,000 years, right up to the modern day, new research suggests.

And it seems to be acting in surprising ways on complex traits encoded by multiple genes, such as those tied to intelligence, mental illness and even cancer.

In natural selection, genes that confer some sort of survival or reproductive advantage get passed down and persist in a population, while those that lead to lower survival or fewer offspring become less common. There's no question that natural selection shaped the evolution of humans in our more distant past. But the impact of natural selection in the recent past is a much more controversial question.

The new research suggests that natural selection is indeed an important factor in modern times, though the methods used in the study have led to missteps before, said John Novembre, a computational biologist at the University of Chicago who was not involved in the new research. This means the findings should not be taken as the final word in modern-day natural selection.

Related: How would Earth be different if modern humans never existed?

The new study focuses on traits that emerge from a combination of multiple gene variants, such as intelligence and skin pigmentation. The complex genetics of these traits makes unraveling the action of individual genes difficult. To find these subtle effects, researchers conduct genome-wide association studies (GWAS), in which they scan for genetic markers across the entire genome to find short genetic sequences that are more common in certain traits than in others.

These results can be challenging to interpret even comparing people at a single point in time. Newer studies up the ante by looking not only for genes associated with complex traits, but also for signs of natural selection on these traits. In essence, genes that become more common over time are under positive selection: They're beneficial in some way and are thus likely to be passed down. Genes that become less common with time are under negative selection. They're somehow harmful to survival or reproduction, and thus are less likely to be passed down.

"There is quite a lot of controversy about whether GWAS is ready for this type of application," Novembre told Live Science.

In their study, published Nov. 15 in the journal Nature Human Behaviour, the researchers found a total of 755 traits showing signs of selection in the last 2,000 to 3,000 years.

For the modern samples, the researchers used data from people of European ancestry in the U.K. BioBank, a repository of genetic and health data from 500,000 participants. To look deeper into history, the researchers also used three datasets of ancient human DNA from the pre-Neolithic, Neolithic and after the advent of agriculture in the Near East, comprising a total of 512 individuals. The researchers looked in three timeframes: The modern era, the past 2,000 to 3,000 years, and up to about 100,000 years ago. The oldest data is the most unreliable, said study leader Guan Nin Ling, a professor in the school of biomedical engineering at Shanghai Jiao Tong University.

While the researchers had detailed health and lifestyle information from the U.K. BioBank, they had only partial genetics to go on for the older samples, and no direct information about things like how many children a person had or what they ate. Thus, they used the genes themselves to infer traits. If a gene known to be involved in height increased in frequency over time, the researchers took that as a signal that height might have been under positive natural selection.

The traits that seemed to be under selection ranged from skin traits such as "ease of tanning" to various body measurements. Somewhat surprisingly, genes associated with some seemingly undesirable traits increased in prevalence over time, including genes associated with conditions like skin cancer, inflammatory bowel disease and anorexia nervosa. This suggests that some of these disorders arise as side effects of genes that are beneficial for other reasons, the researchers suggested.

"If one variant elevates the risk of one disease but decreases the risk of another, natural selection would have little power to eliminate this variant," Lin told Live Science.

Ling and his colleagues were most interested in the question of why disorders with complex genetics, such as schizophrenia or attention deficit hyperactivity disorder (ADHD), persist despite natural selection.

But GWAS can be a tricky tool for trying to unravel natural selection, Novembre told Live Science. One of the biggest problems is something called "stratification." Differences between two populations can appear genetic, when they are actually environmental. Because GWAS can't show that a gene causes a trait, only that they're associated, the results can get weird, fast. To use a classic example from a 1994 paper, chopstick skills are clearly not a gift of DNA: They're a matter of practice from a young age. But a GWAS study in a diverse population like San Francisco might very easily turn up evidence of genes associated with chopstick skills simply by revealing genes that are more common in East Asian populations than in European populations.

This mistake has actually happened. In the last decade, a number of papers came out claiming that height-conferring gene variants are more prevalent in Northern Europe than in Southern Europe and that natural selection was pushing Northern Europeans to become taller, on average, according to research published in 2012 in the journal Nature Genetics.

But it turned out the impact of these genetic variants was overestimated, Novembre said. When looking at those same genetic variants in less diverse populations (a strategy for reducing the stratification problem), the evidence for natural selection vanished. The study had been picking up on so-far-unknown environmental differences between northern and southern Europeans and mistaking them for something purely genetic. Researchers had to completely rethink the results and are still uncertain about whether natural selection has anything to do with height differences across Europe, according to a 2019 paper in the journal eLife.

The use of data from people of only European ancestry helps limit the stratification problem, Novembre said. But there are still opportunities for the stratification problem to arise, he warned.

Among the hundreds of traits the researchers found might be under natural selection, a few stood out. When focusing on modern-day data, the researchers found that higher IQ was associated with having more sexual partners but fewer children. Meanwhile, ADHD and schizophrenia were both associated with having more sexual partners. These two conditions are examples of traits that might be a challenge in daily life, yet improve mating success, Lin told Live Science.

When looking back over more than 100,000 years of human history, the researchers found that traits having to do with skin tone and body measurements were the most common to show selection pressure. These included things like facial measurements, height and torso length. For example, genes associated with face shape and size were apparently under natural selection over the past 100,000 years, the researchers found, which might have to do with changes to the jaw and skull associated with diet and brain growth.

Looking back as far as 3,000 years ago, the researchers found that inflammatory bowel disease seemed to be favored by natural selection. This could be an example of a trait that is helpful in one context and harmful in another, Lin said.

"We hypothesize that in ancient times with poor hygiene conditions, a highly activated immune system in the intestine would protect us from infection," he wrote in an email to Live Science. "However, a highly activated immune system in modern society only causes our intestine to attack itself."

But it can be very hard to show why a particular trait relates to evolutionary success. To use height as an example, being tall might benefit reproduction by making someone more appealing to potential sexual partners. Or maybe height is just a side effect of an efficient metabolism, which improves survival rates, and that increased likelihood of surviving to reproductive age could lead to the genes getting passed down to the next generation. If genes tend to vary together and many do natural selection could be acting on a totally different trait than the one that seems most intuitive. For example, Novembre said, the variants that made skin tanning easier, which showed up as highly selected in the new research, are likely related to a lot of other traits, like rates of skin cancer, freckling and hair color. It's hard to know what path, exactly, leads to someone reaching reproductive age, attracting a fertile mate, and having lots of babies, and which genes are just lucky hangers-ons in that process.

Making matters more complicated, there are times when the genetics of a trait may be completely swamped by the environment. Something like this could theoretically happen with human intelligence. IQ is partially hereditary, so if it's true that higher-IQ people do have fewer children, that would arguably push the collective IQ of the population downward over time. But if the environment became more conducive to brain development better nutrition, reductions in lead or other pollutants the population might well become brighter.

"Just because the apparent genetic basis for something is changing doesn't mean the population has even been evolving in that direction," Novembre said.

One approach to nailing down natural selection would combine large-scale GWAS with studies on the genomes of single families, Novembre said. Family members, especially siblings, usually grow up in fairly similar environments, so it's easier to tell when genes are affecting any given trait. These family studies could be used to ground-truth claims from large GWAS samples, teasing out which genes still show impacts when you remove as much of the environment as possible from the equation.

Lin and his colleagues plan to conduct family studies to learn more about the genetics of complex conditions like schizophrenia. They're also working to quantify genetic variants that can give rise to both beneficial and harmful effects simultaneously, he said. The findings of the new study are a starting point, Lin said, and a reminder that natural selection is still a force in human biology.

"It is simply not true that humans have stopped evolving by natural selection, even given our capacity to change the environment towards facilitating and reducing physical tasks, minimizing the energetic costs to get better food, and better health care system," Lin said.

Originally published on Live Science

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Natural selection has been acting on hundreds of human genes in the last 3,000 years - Livescience.com

Heart attacks struck Sek Kathiresan’s family. He’s devoted his life to stopping them. – BioPharma Dive

Sekar Kathiresan was driving home when his cell phone rang. The voice on the other end belonged to his father. It was the evening of Sept. 12, 2012, his father's 65th birthday. But that wasn't why he was calling.

"Senthil collapsed at home," Kathiresan's father said. "He's in the hospital."

Senthil, Kathiresan's older brother, was a seemingly healthy 42-year-old, training for a race. But that night he returned from a run dizzy and sweating profusely. He called 911, then had a seizure as paramedics arrived.

Senthil had had a heart attack; his brain starved of oxygen for minutes. He died a little over a week later.

His death devastated Kathiresan, an immigrant from India who spent his early childhood overseas with his brother, waiting for the day they'd join their parents in the U.S. "We relied on each other," Kathiresan said. Both had thrived in the U.S. They were married the same year and each had young children.

This story might be familiar to the millions of people and families affected by heart disease, the world's leading cause of death. But it's more than that for Kathiresan, who, when Senthil died, was a cardiologist and emerging as one of the field's leading geneticists.

"It really shook Sek. It shook all of us," said David Altshuler, the former Broad Institute of MIT and Harvard geneticist, a Vertex Pharmaceuticals executive and mentor to Kathiresan. "It was a tragic irony."

Kathiresan channeled his despair into motivation. He rose to the top of his profession, making discoveries that changed the way people think about heart disease. He launched a startup with an exceptionally ambitious aim to prevent heart attacks, for life, with a single treatment. Nearly a decade after his brother's death, the startup, called Verve Therapeutics, could soon test that treatment in people.

"I tried to turn that negative energy into Verve," Kathiresan said, "to make sure what happened to Senthil doesn't happen to others."

The road ahead is daunting still. Kathiresan is an academic-turned-CEO on a personal mission, not a seasoned biotech executive. His company is attempting a scientific moonshot, relying on cutting-edge, but unproven, gene editing technology to develop a one-time medicine for one of the most prevalent diseases. In doing so, he will have to prove the world needs what is essentially a longer-lasting version of cholesterol-lowering drugs that are already available.

"It's a pretty high bar to say gene editing has an important role to play here," said Richard Lifton, the president of Rockefeller University and a geneticist known for research into heart disease.

"But the flip side of that," he added, is a drug "that could last, potentially, a lifetime."

Kathiresan was only four years old when his world upended.

Kathiresan's father, an aspiring engineer, had received a full scholarship at the University of Pittsburgh, thousands of miles away from the tiny southern India village of Viramathi he, his wife and three children called home. He dreamed of coming to the U.S. and pursuing a higher education, but couldn't afford to bring the whole family, Kathiresan said. So, in 1975, he left for the U.S. with his wife, baby daughter Davi and about $40. Sek and Senthil stayed in India.

Kathiresan remembers a sense of loss, a "yearning." He didn't see his parents or hear their voices for five years. There were no phones in the house the brothers shared with their grandparents, nor at the boarding school they attended. They communicated through letters sent across the ocean. "I'm not sure I would have had the courage to leave my kids behind," he said, reflecting on his father's decision.

But the plan worked. Kathiresan's father earned a Ph.D. and saved enough money to bring his sons to the U.S.

Kathiresan vividly remembers the flight from Mumbai to New York. The brothers, who had never seen a plane before, were awestruck. They flew by themselves, with an attendant as their guardian. Picked up at the airport by their father, their first meal in the U.S. was at McDonald's, where Kathiresan had french fries for the first time. He devoured them and asked for more.

"We can't afford another one," his father told him.

The Kathiresan family in 1975. Sek is second from left. Courtesy of Sekar Kathiresan

Senthil and Sek Kathiresan, aged 10 and 9, in India in 1980, just before leaving for the U.S. Courtesy of Sekar Kathiresan

The Kathiresan family soon moved into a house outside of Pittsburgh. The brothers, who spent half their childhood in a town with no running water, would live the other half in a middle-class and predominantly White U.S. suburb, an upbringing each wrestled with.

Growing up, Kathiresan was one of the few people of color in his school. Though he made fast friends, he wasn't comfortable, caught between his two worlds: weekly prayers at a nearby Hindu temple and weekend football games at school. His mother pushed him and Senthil to remember their heritage, anxious they would become "too American."

While Kathiresan dated and met his wife in college, Senthil had an arranged marriage. "We respected each other's approach," he said. "Some immigrants want to jump right in and be all in," and others "want to keep as much of their home culture as possible."

Kathiresan majored in history and even flirted with a career in finance before finding medicine, which he said "offered a sense of purpose and a mission."

His choice of profession was also personal, even before Senthil's death. Kathiresan's uncle, a physician, had died of a heart attack. So had his grandmother. His father had a heart attack at 54. Each time Kathiresan was more certain he'd become a cardiologist.

He embraced the grueling hours and sleepless nights that came with residency training at Massachusetts General Hospital, undeterred even when accidentally stuck by a needle that had been in the neck of an HIV patient. "I saw my whole life flash in front of me," he recalled, yet, after initially panicking, he took antiviral drugs and went back to the hospital.

"It comes with the territory," he said. "You're teaching, you're trying to help, but there's risk, you know?"

Kathiresan wasn't satisfied being a doctor, though. He wanted to understand why the people closest to him were getting sick and learn how to do something about it.

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David Altshuler recalls sitting in his office at MGH one morning in 2000 when he heard a knock on the door.

Altshuler was already well on his way to being recognized as one of the world's top geneticists. His academic lab would soon co-lead three large genetic research studies the 1,000 Genome Project, the SNP Consortium and the International HapMap Project and he would become one of the founding members of the Broad Institute.

Kathiresan, then a young cardiology fellow, sought him out and burst into his office.

"I want to figure out what causes people to have premature heart attacks," Kathiresan exclaimed, according to Altshuler.

Dressed in scrubs, Kathiresan looked exhausted, having gone to Altshuler's office straight from an overnight shift at the hospital. Altshuler can still recall the big, dark circles under Kathiresan's eyes.

Many people can talk a good game. But Sek is the real deal. He reminds us of why we do what we do.

David Altshuler, chief scientific officer of Vertex Pharmaceuticals

"How are you going to do that?" he asked.

Kathiresan laid out a plan to discover what puts people at risk for heart attacks. Then he'd figure out which risk factors were actually important, before finding a way to intervene before health problems began.

"I need to learn genetics," Kathiresan told Altshuler. "That's why I'm here."

Altshuler was impressed. "He was personally compelling," he said, "and obviously incredibly motivated." When Kathiresan finished his doctoral training three years later, he went to work for Altshuler at the newly founded Broad Institute.

Kathiresan (front row, third from left) during his time as chief resident in internal medicine at Massachusetts General Hospital. Source: Sekar Kathiresan

The experience was a crash course in genetics. Altshuler pushed Kathiresan to answer scientific questions that mattered, not just the ones he could solve. He taught Kathiresan how to manage and develop talent, skills he'd call on in the future. "He had an immeasurable influence on me," Kathiresan said.

Over the next decade, the two wrote grants together and teamed up on studies aimed at identifying genetic markers for heart attacks. They became good friends and confidants. Along the way, Kathiresan emerged as "the leading person in the world studying the genetics of coronary artery disease, certainly of his generation," Altshuler said.

"Many people can talk a good game," Altshuler said. "But Sek is the real deal. He reminds us of why we do what we do."

A research lab is like a small company. There's money to raise, a budget to manage. A team to put together, mold and motivate. Careers to foster and a vision to rally a team around. Kathiresan got that chance in 2008, when he started a lab at MGH and the Broad to search for genetic clues into the underpinnings of heart disease.

As a first-time lab leader, Kathiresan had to convince people to believe in him. One of the first was Kiran Musunuru, a young heart doctor doing a fellowship at Johns Hopkins University.

At the time, Musunuru was disillusioned with cardiology. There were plenty of ways to treat heart disease, he said, but not enough tools to prevent it. Musunuru thought genetic research was the key and desperately wanted to be a part of the building "wave" of studies. That led him to Kathiresan's lab at MGH.

Kathiresan didn't have experience. His lab was brand new and his future there wasn't secure. But Musunuru felt a kinship with him. "In the same way that I was, he was all in," he said. "You've got to take some risks, right?"

Kiran Musunuru, professor of cardiovascular medicine and genetics at UPenn Source: American Heart Association

What followed was a prolific partnership. Musunuru became Kathiresan's mentee, one of his first post-doctorate students, and eventually, the head of his own lab at the University of Pennsylvania and a Verve co-founder. They were willing to put in "insane amounts of time" to finish work and publish papers as quickly as possible, according to Musunuru. Conditioned by working long hospital shifts, they'd each wake up before dawn, texting and calling one another.

The two partnered on a number of important research papers, looking into, among other things, the genetic basis of cholesterol and a protective gene known as ANGPTL3 that would become a top therapeutic target of drugmakers including, years later, Verve.

In the meantime, Kathiresan's lab turned into a training ground for dozens of other young scientists. By the time he stepped away, Kathiresan taught more than 60, many of whom are now faculty members. And he had discredited a long-held belief about heart disease.

For many years, Ethan Weiss, a cardiologist at the University of California, San Francisco, told his patients to exercise so their levels of "good cholesterol" would increase. He wasn't alone. Doctors were taught in medical school that high levels of high-density lipoprotein, or HDL, were associated with fewer heart attacks. Conventional wisdom was "you wanted to do everything you could to get your HDL up," Weiss said.

But researchers didn't know much about HDL and its relationship to fats in the blood called triglycerides, which were also linked to heart disease. High HDL, for example, was associated with low triglycerides and vice versa. "The question has been, which of these is the dominant one? Which one carries risks?" said Lifton, of Rockefeller. "It's been very hard to disentangle."

Researchers and drugmakers were nonetheless convinced HDL was the key, and that medicines that raised it would prevent heart attacks. Years of research led to drugs, known as CETP inhibitors, that could boost HDL. Several were thrust into large clinical trials early last decade, poised to become the next big thing in heart medicine.

"But correlation," Kathiresan said, "does not mean causation."

He basically changed a paradigm that we had clung to forever.

Ethan Weiss, cardiologist at the University of California, San Francisco

In 2012, Kathiresan's lab at MGH made a startling discovery: Good cholesterol isn't so good after all. By studying the genes of more than 100,000 people, they separated the effects of triglyceride levels from HDL. They found people with more HDL weren't safer from heart attacks.

HDL appeared to be a mirage, its link to heart disease perhaps conflated with other factors. Drugs that raise it likely wouldn't protect people from heart attacks, the team wrote in a paper published in The Lancet in May 2012.

The news stunned cardiologists. "He basically changed a paradigm that we had clung to forever," said Weiss, who now tells patients to ignore HDL levels because "it doesn't seem to matter."

The findings rippled across the pharmaceutical industry. One by one, CETP inhibitors from Roche, Amgen, Merck & Co. and Eli Lilly failed in clinical trials or were dropped by their developers. The class was largely shelved, along with a long-running hypothesis.

"It was a beautiful demonstration of using large-scale genomics to address a clinically vexing and important problem," Lifton said.

Just a few months after the paper's publication, Kathiresan's brother died of a premature heart attack.

Kathiresan took time off work and reexamined his own health. He went for heart tests, committed to being more active and dropped weight hed put on in college but hadn't lost.

"You mourn," Kathiresan said, and then "focus on the things you have control over."

So Kathiresan kept going. He and his labmates found more genes associated with either risk of early heart attacks or protection against them, confirming research by others in the process. They used a trove of genetic data from the U.K. to develop a diagnostic test that can identify higher risks of coronary artery disease, diabetes and other conditions in seemingly healthy people. "He decided, 'I will redouble myself to this effort,'" Altshuler said. "That took courage."

David Altshuler, Vertex's chief scientific officer Source: Vertex Pharmaceuticals

By 2018, they'd amassed a body of work so impactful that Kathiresan received the same Curt Stern award an honor given to pioneering human geneticists by the American Society of Human Genetics that Altshuler previously won.

In his acceptance speech, Kathiresan recalled the journey that took him from a small town in India to an awards stage in San Diego.

He then showed an ambulance report from the 911 call a 42-year-old made before he suffered a heart attack. He shared the man's electrocardiogram, his cholesterol and triglyceride levels and troubling family history. He explained how he died. He went through all the work he and his team had done to understand why the same thing happens to millions of other people.

The patient was his brother, he explained. New drugs were needed to avert the same tragedy in others, he said, and that was something he was working on. A high-profile competition he had recently lost gave him an opportunity.

Kathiresan, accepting the Curt Stern award from the American Society of Human Genetics on Oct. 18, 2018. Source: American Society of Human Genetics, via YouTube

In January 2016, the American Heart Association, the British drugmaker AstraZeneca and Google's life sciences arm Verily came up with an idea for a competition. Called "One Brave Idea," they promised a $75 million award and partnership opportunities to a researcher with the best idea to cure heart disease.

"What we're seeing is this growing epidemic of cardiovascular disease worldwide," said AHA CEO Nancy Brown, in a video describing the competition, "and we know that we need a new answer."

The AHA received 349 applications from research teams in 22 different countries. Kathiresan submitted one of them. Musunuru, then at UPenn, wrote another.

Unknown to one another, both pitched the same idea: a single shot of a gene editing drug that could drive down "bad cholesterol," or LDL, as low as possible for as long as possible.

Kathiresan cowrote an application with Anthony Philippakis, another Altshuler trainee who worked with the venture firm GV; and Feng Zhang, also of the Broad and one of the leaders of CRISPR gene editing research. Musunuru's team included UPenn gene therapy pioneer James Wilson.

The proposals were "eerily similar," Musunuru said. "Almost interchangeable."

Neither even made it to the competition's final round. The award went to a group of researchers led by Calum MacRae, chief of cardiovascular medicine at Brigham and Women's Hospital, who won for a genomics project meant to detail the biological changes that occur when heart disease begins.

The loss still bothers both of them. "I was bitterly disappointed," Kathiresan said. Musunuru calls it a "big, lost opportunity for the AHA."

Musunuru turned his attention back to research. Kathiresan decided to change careers.

Academia and the drug industry are closely linked. Academic researchers, after all, often make the discoveries that companies turn into medicines.

But that doesn't make it easy to leave the research bench for an industry job. The switch involves learning an entirely new language. Kathiresan, for example, had never heard the term "CMC," which is industry parlance for the process and regulation of drug manufacturing.

Jumping from academia to biotech can also mean giving up a secure position for a role in a company that, history would suggest, is likely to fail. Scientific glory isn't the only goal for a biotech, either: it has to eventually make money.

Kathiresan said he didn't have the "antipathy to the for-profit model that some people have." Previously, he had been focused on research, turning down industry job offers along the way. But his perspective changed after Altshuler left the Broad Institute in 2015 for a job as Vertex's top scientist. That "opened my eyes to the fact that there's a much larger world out there, and ways to have impact," he said.

So after losing the One Brave Idea competition, Kathiresan turned to Philippakis. It was a role reversal, of sorts: Kathiresan had advised Philippakis throughout medical school and after. "I really consider him a mentor in my life," Philippakis said.

Now it was Kathiresan who needed help. Philippakis cowrote the AHA application, he said, to help figure out how to build a company around the one-shot project. And Philippakis, who was well-versed in the biotech business because of his role with GV, could teach Kathiresan how to make that happen.

For almost two years, they gathered a small group every Friday to go through all the steps and potential roadblocks ahead. They tried to convince themselves "that this was actually doable," Philippakis said. They discussed how and where they'd get the intellectual property. The type of gene editing medicines they'd make. The business plan. How to raise the money and which firms to contact. Who the founders would be.

They came up with the name Endcadia Therapeutics a nod to ending coronary artery disease and prepared a pitch for GV.

Krishna Yeshwant is a venture capitalist who has worked with GV since its inception more than a decade ago. Over that time he's invested in dozens of healthcare startups. He's been asked to back plenty more.

Yeshwant has heard plenty of stories like the one Kathiresan told. Different versions of how "this family member of mine, this boyfriend or girlfriend, came down with this condition and I've devoted my life to it," he said. An emotional pitch only goes so far, though. And venture capitalists don't often invest in heart drugs because of how expensive they are to develop and test. In recent years, they've taken a back seat to promising new cancer and rare disease medicines.

But Yeshwant, who had joined Kathiresan and Philippakis for many of those Friday morning meetings, thought they were on to something. The treatment they envisioned, if successful, could change "how society works," he said, and Kathiresan was devoted to seeing it through. The plan they'd laid out was realistic as well: First they would prove the drug could work in a rare, inherited heart disease, a faster and less expensive clinical development path. Then they would go bigger and broader.

"It's aspirational," Yeshwant said, "but there was a nice on-road to it."

Krishna Yeshwant, managing partner at GV Source: GV

The others agreed. The startup became the first drugmaker GV better known for forming digital health companies ever incubated. The firm led a $59 million financing that closed in August 2018 and was announced the following year.

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Heart attacks struck Sek Kathiresan's family. He's devoted his life to stopping them. - BioPharma Dive

Animal Genetics Market Worth ($7,705.23 Mn by 2027) by (6.3% CAGR) with Impact of Coronavirus Outbreak and Global Analysis & Forecast by The…

Growth of Animal Genetics Market is attributed to rise in production of porcine and increase in pork consumption across the globe. The same segment is likely to register highest CAGR in the global animal genetics market during the forecast period.

PUNE, India, Nov. 25, 2021 /PRNewswire/ -- According to The Insight Partners study on "Animal Genetics Market to 2027 Global Analysis and Forecast by Animal Genetic Material, Genetic Material and Service" the animal genetics market was valued at US$ 4,778.67 million in 2019 and is projected to reach US$ 7,705.23 million by 2027; it is expected to grow at a CAGR of 6.3% during 20192027. The growth of the market is attributed to the growing preference for animal derived proteins supplements and food products and rising adoption of progressive genetic practices such as artificial insemination (AI) and embryo transfer. However, limited number of skilled professionals in veterinary research and stringent government regulations for animal genetics is expected to hinder the market growth.

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The North American region holds the largest market share of this market and is expected to grow in forecasted years. The growth in North America is characterized by the presence of new market players, various product launches and increasing government initiatives.

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Likewise, Mexico is likely to offer attractive business opportunities for livestock genetics. Over the last decades, Mexico's beef, pork, and dairy productions have undergone valuable developments. Mexican generators in the expanding livestock intensive systems are frequently using modern genetic improvement technologies such as artificial insemination and embryo transfers.

In North America, the US is the largest market for animal genetics market. Livestock groups provide consumers with different products and services, including meat, milk, eggs, fiber, and draught power. The genetic variation within livestock communities produces the raw material for evolving through natural selection in answer to changing conditions and human-managed genetic improvement plans. As per the Food and Agriculture Organization (FAO), animal genetics is one of the livestock development support. It is a wide field, ranging from characterization to conservation to genetic development. According to the National Institute of Food and Agriculture (NIFA), there have been dramatic improvements in animal production yields and efficiencies. Therefore, the ever-increasing demand for dietary protein in the United States has been observed. These demands are achieved by one the best Animal breeding is one strategy by which these improvements may be performed. NIFA, with the help of scientists from universities and research organizations and food animal industries, provides national leadership and funding opportunities to conduct basic, applied, and integrated research to increase knowledge of animal genetics and genomics.

Story continues

The COVID-19 outbreak has disturbed various trades and businesses across the world. The incidence of corona virus or COVID 19 has not yet been registered the animals. Also, there is no evidence that companion animals are the prime source of the spreading epidemic in humans. However, various studies have been conducted to check the spread of disease from animals to humans. In many cases, zoonotic diseases were found in humans due to interaction with animals. Therefore, government bodies are taking more precautions and safety measures to prevent the spread of corona virus in the animals. The measures are widely carried out for companion animals as they frequently come in contact with their owners. Also, it is essential to report the cases to a veterinary authority. For instance, in the region, to report the cases of detection of COVID-19 is done to OIE through WAHIS, in accordance with the OIE Terrestrial Animal Health Code as an emerging disease.

The OIE is actively working by providing assistance to research for their on-going research and other implications of COVID-19 for animal health and veterinary public health. The assistance is also providing risk assessment, risk management, and risk communication. Also, the OIE has put in place an Incident Coordination System to coordinate these activities. In addition, OIE is also working with the Wildlife Working Group and other partners to develop a long-term work program. The aims are to provide better understandings, dynamics, and risks around wildlife trade and consumption. Also, it aims to develop strategies to reduce the risk of future spillover events.

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Additionally, various product and service launches have been initiated, which is helping the US market to grow. For instance, The Veterinary Genetics Laboratory (VGL) at the UC Davis School of Veterinary Medicine has launched an updated and advanced website along with several new tests for veterinary community. As the VGL is one of the foremost genetic testing laboratories in the world, the new site and tests will bring yet another level of global impact to the top-ranked veterinary school. Thus, the consistent support for combating addiction in the country undertaken by various organizations likely to augment the growth of animal genetics market during the forecast years.

The Asia Pacific region is expected to be the fastest-growing region among all other regions. The growth of the market in the region is majorly due to countries like China, India and Japan, which drives the major consumption of animal derived products. Moreover, growing preference for animal derived proteins supplements and food products, and rising adoption of progressive genetic practices such as artificial insemination (AI) and embryo transfer are also likely to contribute to market growth. On the other hand, significant investment by government in various breeding programs is supporting the growth of market. For instance, the central and local governments have invested more than RMB 5 billion to build breeding or multiplier farms and conservation farms for breed improvement programs and the building of centers for testing the quality of breeding stock, semen, and embryos.

Based on product, the animal genetics market is segmented poultry, porcine, bovine, canine, and others. The porcine segment accounted for more than 35.84% of the market share in 2019. In terms of genetic material, the animal genetics market is segmented into semen, and embryo. The embryo segment held the largest share of the market in 2019. In terms of service, the animal genetics market is segmented into DNA typing, genetic trait tests, genetic disease tests, and others.The DNA typing segment held the largest share of the market in 2019.

Rising Adoption of Progressive Genetic Practices Such as Artificial Insemination (AI) and Embryo Transfer in Animal Genetics Market:

Growing focus on developing superior animal breeds using genetic engineering to obtain high reproduction rates for large-scale production of modified breeds is expected to drive animal genetics market during the forecast period. Animal genetics emphasizes the inheritance and genetic variations in wild and domestic animals. This science is used at a commercial level for services such as testing genetic disorders, screening genetic traits, and typing DNA. For identifying genetic hybridizations, animal genetics uses various genetic practices, such as artificial insemination, embryo transfer, and cytological studies. Moreover, artificial insemination (AI) can reduce various risks involved in animal breeding and disease transmission. It is found that female offspring cattle born through artificial insemination yield more milk than normal offspring. Additionally, the use of antibiotic-containing semen extensors is effective in preventing bacterial infectious diseases. Therefore, the entire AI process is considered hygienic than natural mating.

The market players are focusing on partnerships, collaboration, and acquisitions to develop genetically modified breeds and maintain their market share. For instance, in August 2020, Cogent and AB Europe collaborated to launch a novel sexed semen service for sheep producers in the UK. In May 2018, Recombinetics entered into partnership agreement with SEMEX for the implementation of a precision breeding program, which is expected to improve animal health and well-being through hornless dairy cattle genetics. According to the Brazilian Association of Artificial Insemination, the number of commercialized doses of semen increased from 7 million in 2003 to ~14 million in 2017. Thus, rising adoption of genetic practices will support the market growth in coming years.

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Market: Segmental Overview

In terms of product, porcine segment is anticipated to register the highest CAGR during the forecast period. Growing production of porcine and increase in pork consumption is likely to favor the growth of the market. Pork is the most consumed meat across the globe. In the US, pork production generates $23.4 billion output per year. Additionally, 26% that is around 2.2 million metric tons of pork and its products are exported to other countries. Despite of the challenges such as tariffs, labor and disease risks, the pork industry in US is still growing with around 66,000 sows in 2019. Also, developments by the major pork producers in the country is likely to grow the pork production industry. For instance, in 2017, 123-year-old Clemens Food Group partnered with 12 independent hog farmers to establish a new packing plant in Michigan. Thus, growing pork production industry is likely to favor market growth. In terms of genetic material, the animal genetics market is segmented into semen, and embryo. The embryo segment held the largest share of the market in 2019. In terms of service, the animal genetics market is segmented into DNA typing, genetic trait tests, genetic disease tests, and others.The DNA typing segment held the largest share of the market in 2019.

Animal Genetics Market: Competition Landscape and Key Developments

Neogen Corporation, Genus, Groupe Grimaud, Topigs Norsvin, Zoetis Services Llc, Hendrix Genetics Bv, Envigo, Vetgen, Animal Genetics Inc, Alta Genetics Inc. and among others are among the key companies operating in the animal genetics market. These players are focusing on the expansion and diversification of their market presence and the acquisition of a new customer base, thereby tapping prevailing business opportunities.

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In September 2020, Genus Plc and Tropic Bioscience entered into collaboration. Tropic Biosciences the pioneering agricultural-biotechnology company entered into collaboration with Genus in order to explore the application of Tropic's Gene Editing induced Gene Silencing (GEiGS) technology in porcine and bovine genetics.

In July 2020, Topigs Norsvin entered into strategic partnership with Acuity swine genetics company. This partnership will provide the opportunity for joint collaboration and expansion of technical expertise, commercial product testing and supply chain infrastructure in animal genetics market across the North America region.

In April 2020, Zoetis Animal Genetics and Angus Australia have entered into a strategic partnership that will aid Australian Angus breed stock and commercial breeders an additional benefit from genomic, or DNA-based technology. Zoetis have made a considerable investment in the expansion of the Angus genomic reference population through the provision of genotyping services and sponsorship.

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Animal Genetics Market Worth ($7,705.23 Mn by 2027) by (6.3% CAGR) with Impact of Coronavirus Outbreak and Global Analysis & Forecast by The...

Exercise may lower inflammation by increasing endocannabinoids – Medical News Today

Cannabis exerts its effects on the body by binding to cannabinoid receptors. These cannabinoid receptors also bind to endogenous cannabinoids that the body makes, called endocannabinoids.

Endocannabinoids are involved in the modulation of numerous biological processes, including metabolism, pain, inflammation, and transmission of information in the brain. The release of endocannabinoids, along with opioids, is also responsible for the feeling of euphoria that people generally experience after an intense workout.

A new study has shown that daily physical exercise is effective in lowering the levels of inflammation-related markers. Moreover, the study suggests that the endocannabinoid system may interact with gut microorganisms to produce such a reduction in inflammatory markers.

Researchers at the University of Nottingham led the research, which appears in the journal Gut Microbes.

Endocannabinoids bind to cannabinoid receptors present in the brain, peripheral nervous system, and immune system. The enteric nervous system, which controls the gut, also expresses cannabinoid receptors.

The dysregulation of the endocannabinoid system is associated with obesity and metabolic disorders.

Microorganisms present in the gut, which people collectively refer to as the gut microbiota, also have a significant influence on metabolism. Changes in the composition of these microorganisms, including reduced diversity of gut microorganisms, are associated with obesity and other metabolic disorders.

Studies suggest that the endocannabinoid system interacts with the gut microbiota to influence metabolism and energy homeostasis.

For instance, gut microbiota composition can influence endocannabinoid and cannabinoid receptor levels in the intestine. Specifically, changes in gut microbiome composition in obesity occur alongside lower endocannabinoid levels.

Obesity and other metabolic disorders are also associated with chronic, low grade inflammation. Both endocannabinoids and gut microbiota are involved in the modulation of inflammation, including in the aforementioned conditions.

Certain gut bacteria species can break down dietary fiber to produce short-chain fatty acids. These short-chain fatty acids have a link with lower inflammation and may exert protective effects against obesity.

Similarly, the endocannabinoid system can limit inflammation, and changes in the endocannabinoid system are observed in irritable bowel syndrome (IBS) and obesity.

Scientists do not fully understand whether the short-chain fatty acids that gut microorganisms produce can interact with the endocannabinoid system to produce anti-inflammatory effects.

The present study reports that the endocannabinoid system may mediate, in part, the anti-inflammatory effects of short-chain fatty acids that the gut microbiota produces, and vice versa.

Exercise is associated with an increase in endocannabinoid levels and long-term anti-inflammatory effects. The researchers used a 6-week exercise intervention to investigate further the association between endocannabinoids, inflammation, and short-chain fatty acids produced by gut microorganisms.

The researchers found that physical exercise was associated with lower inflammation, which higher short-chain fatty acid and endocannabinoid levels accompanied.

The studys first author, Dr. Amrita Vijay, a research associate at the University of Nottingham, told Medical News Today:

The findings from the current study highlight that simple lifestyle interventions such as exercise can modulate endocannabinoids, and this is a timely discovery, especially in the time when there is increasing interest around the use of cannabidiol and other related supplements in reducing levels of inflammation.

The present study involved two cohorts. The first cohort consisted of 78 adults who were aged over 45 years, living with knee arthritis, and residing in a community setting.

The researchers examined the relationship between the endocannabinoid system, gut microbiota, and inflammation in this cohort at baseline. They then confirmed these results in a second cohort consisting of 35 individuals over 18 years of age.

The researchers also assessed the effects of a 6-week exercise intervention tailored to people with osteoarthritis on the relationship between the endocannabinoid system, inflammation, and gut microbiota in the first cohort. To do this, they divided the participants into a treatment group, consisting of 38 participants, and a control group, involving 40 individuals.

The researchers used blood samples from the participants to evaluate the serum levels of endocannabinoids, short-chain fatty acids, and inflammatory markers. The inflammatory markers included cytokines, a class of immune proteins that have either pro-inflammatory or anti-inflammatory effects.

The team used stool samples and conducted DNA sequencing to assess the abundance of various gut microbiota species.

Before the onset of the exercise intervention in the first cohort, the researchers found that endocannabinoid levels had a positive correlation with gut microbial diversity, short-chain fatty acids levels, and levels of gut microbiota species that produce these short-chain fatty acids.

In contrast, higher endocannabinoid levels were associated with lower levels of Collinsella, a gut bacteria genus that is linked with increased inflammation.

Consistent with these results, endocannabinoid levels were positively correlated with anti-inflammatory cytokines levels but had a negative relationship with pro-inflammatory cytokine levels. These results from the first cohort were similar to those that the team obtained from the second cohort.

The researchers then estimated the contribution of endocannabinoids to mediating the anti-inflammatory effects of short-chain fatty acids. They used a statistical method called mediation analysis, which can help estimate the extent to which a third factor plays a role in mediating the relationship between two variables.

They found that endocannabinoids mediated roughly one-third of the effects of short-chain fatty acids on inflammatory markers. This suggests that other biological factors or pathways, in addition to the endocannabinoid system, may play a role in mediating the anti-inflammatory effects of short-chain fatty acids that the gut microbiome produces.

Likewise, the researchers investigated the extent to which short-chain fatty acids mediated the effects of endocannabinoids on inflammation. They estimated that short-chain fatty acids mediated about half of these effects.

However, the authors caution that such estimates, which they obtained using mediation analysis, do not imply causality.

Next, the researchers examined how the 6-week exercise intervention affected the association between endocannabinoids levels on one hand and short-chain fatty acid levels, gut microbiome composition, and inflammatory markers on the other.

They found that endocannabinoid and short-chain fatty acid levels increased in the exercise group but did not show any changes in the control group. At the same time, there was a decline in the level of pro-inflammatory cytokines in the participants in the exercise group.

Changes in the levels of the endocannabinoid anandamide correlated with the short-chain fatty acid butyrate after 6 weeks across the two groups. Moreover, the researcher found a positive correlation between the changes in endocannabinoid levels and the increase in the abundance of short-chain fatty acid-producing bacteria.

On the other hand, changes in endocannabinoid levels were negatively correlated with the changes in the abundance of bacteria and cytokines associated with pro-inflammatory effects.

Lastly, the endocannabinoid levels were positively associated with the expression levels of the genes for the short-chain fatty acid receptor FFAR2 and the cannabinoid receptor CNR2.

The short-chain fatty acid receptor is associated with a lower risk of obesity, whereas CNR2 is associated with anti-inflammatory effects.

These results suggest that the anti-inflammatory effects resulting from physical exercise could potentially involve an interaction between endocannabinoids and short-chain fatty acids.

Highlighting the studys salience, Dr. Vijay said, The findings are novel, as we may have found a key link between how substances produced by gut microbes interact with the substances produced by our own bodies, which tell us how physical exercise reduces inflammation.

The authors note that their findings are observational and do not establish causation. Furthermore, Dr. Vijay added, The exercise intervention we carried out was performed in individuals with painful knee osteoarthritis and may not be directly relevant to other groups.

It would be interesting to test if different forms of exercise have different effects on our bodies in relation to the levels of these substances being produced and thereby influencing inflammation. It is also important to consider the effect of diet on these relationships.

Dr. Vijay

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Exercise may lower inflammation by increasing endocannabinoids - Medical News Today

Amgen To Present At The 2021 Evercore ISI Healthcare Conference – Yahoo Finance

THOUSAND OAKS, Calif., Nov. 24, 2021 /PRNewswire/ -- Amgen (NASDAQ:AMGN) will present at the 2021 Evercore ISI Healthcare Conference at 5:10 p.m. ET on Tuesday, Nov. 30, 2021. Rob Lenz, M.D., Ph.D., senior vice president of Global Development at Amgen will present at the conference. Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen's business given at certain investor and medical conferences, can be accessed on Amgen's website, http://www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit http://www.amgen.com and follow us on http://www.twitter.com/amgen.

CONTACT: Amgen, Thousand Oaks Megan Fox, 805-447-1423 (media)Trish Rowland, 805-447-5631 (media)Arvind Sood, 805-447-1060 (investors)

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How experts have deployed data to tackle Covid-19 and plan for future pandemics – The Scotsman

It involves understanding human behaviour, addressing inequalities, optimising our communications. It brings in public health and how that interacts with animal health, and then there is the economics lurking behind that. In parallel, there is a whole gamut of aspects to do with education.

Whitelaw says that Scotland, and specifically the University of Edinburgh, is ideally positioned to take advantage of the One Health agenda because of its expertise in human and animal health and in data.

He adds: Edinburgh has a joint medical and vet medical college, a leading science and engineering college and the wonderful humanities, arts and social sciences in the third college. It is not individually that we can address One Health, it is by bringing all these together, by intertwining roles and ideas, that we will achieve success, or do One Health data better.

But how has the One Health approach of collaboration and data sharing between scientists, health practitioners and the wider academic community helped shape our efforts to understand and tackle the coronavirus pandemic? And, building on the achievements already made, how better prepared are we for another global virus outbreak?

Dr Sam Lycett, a genetics expert at the University of Edinburgh, uses phylodynamics to study the spread of viruses. She says: This technique makes use of the now large collections of virus genome sequence data and the fact that these viruses accumulate mutations over time.

She uses this information to look at who infected whom either at an individual level or group level, such as a city or region. Going deeper than this we can also estimate predictive factors for why we see the transmission patterns. Is it just distance, known host movement patterns or a change in environmental conditions?

During the coronavirus pandemic, the amount of available data has been huge, Lycett says. In this current pandemic, there has been a massive global and UK-specific Sars-CoV-2 sequencing effort for people there are almost four million genomes now, with almost one million just in the UK and close to 100,000 just for Scotland.

This is a really good surveillance sample roughly, we are sequencing one in five or six positive cases. We use this sequence data to calculate how individual lineages and mutations are being generated, imported, and growing and declining, in Scotland.

Dr Kenny Baillie, a senior clinical research fellow at the Roslin Institute, says viral sequence data is now converging with clinical and biological data from humans and being used to find treatments for Covid-19.

The Roslin Institute is leading the most powerful study of human genetics of Covid more powerful in terms of discovery power than all of the other genetics studies in the world put together, says Baillie. Most recently, we have reported25 genetic associations with critical illness in Covid, many of which lead us to promising therapeutic avenues.

Discoveries reported after only five months of Covid being in the UK included two genes which have led directly to treatments being included in large-scale clinical trials.

In the future, Baillie wants to be able to look at treatments even more quickly than the five months which was achieved in the pandemic. We can move towards doing this in real time there is a convergence between animal and human science which means the same statistical techniques are used for both livestock and human genetics. With computing power and the human resource that is being deployed, we can move towards close to real-time host and viral genetic studies.

The study of zoonotic pathogens those that can move from animal to a human is at the heart of discovering the way coronavirus spreads, both locally and globally.

Virologist Christine Tait-Burkard, a research fellow at the Roslin Institute, has been working on coronaviruses for more than 12 years. She says: Coronaviruses have an inherent potential for cross-species transmission as one of the properties they have is that they can swap large parts of their genome relatively easily, and that is a bit reminiscent of the most known zoonotic virus, the influenza virus.

International data accumulation and sharing has helped build understanding of coronavirus. Tait-Burkard says this includes looking at treatments for other diseases, such as cardiac conditions and cancer, which can help develop help with coronavirus we can harness that and also tackle coronavirus.

And she says the drugs needed should be taken as early as possible, not when a patient has had to be hospitalised. We really need a pill that people can take at home when they get the first symptoms.

Tait-Burkards work with international colleagues includes looking at the livestock, the wildlife and the human coronaviruses and finding the commonalities, taking all the data together so that we can get drugs that are there for any future pandemic.

We need to leverage lessons from Covid, says Professor Ross Fitzgerald, personal chair of molecular bacteriology at the University of Edinburgh. His work focuses on antimicrobial resistance (AMR), described as a slow pandemic and a huge public health threat, with estimates suggesting hundreds of thousands of deaths occur worldwide due to infections caused by resistant bacteria. This is a major health crisis that has taken a back seat since the pandemic, he says, warning that effective antibiotics could run out.

A lot of the work to find a solution to AMR surrounds data, says Fitzgerald faster diagnostics, more sequence information and real time surveillance of humans, animals and the environment on a global scale.

And he adds that the work on coronavirus can now help tackle AMR. We need to unite academia, industry, government and policy-makers so we are all working together, communicating the data effectively to address the impact of AMR.

Fitzgerald is concerned there is not sufficient volume of data to address AMR at the moment. We need more data, but to get the value from it we need to have really good descriptive information it is high-quality data that we need.

And he is a strong advocate of developing artificial intelligence and machine learning to harness that data. We know that it will allow us to track the emergence and spread of resistance and pathogens.

Professor Lisa Boden, chair of population medicine and veterinary public health policy at the University of Edinburgh, says that from a One Health perspective, there have been issues surrounding the way coronavirus has been dealt with.

She says: Covid-19 has really made visible different types of vulnerabilities in our institutions, our governance and our legal structures, and those are really due to entrenched health, social, racial, political and economic inequalities at different scales, at a local and international level.

Boden says there has been a lack of complete data particular for people living on the edges of society and those people who are living in communities which might be remote, rural and geographically isolated.

To change this, she advocates a non-linear approach which looks at both the causes of inequality as well as at a disease itself, using multi-sectoral datasets.

But with the experience of a vast amount of data collection, use and sharing surrounding the pandemic, some believe future outbreaks could look a lot different.

Lycett says: We will be able to predict and quantify the risk of having a pandemic. Whether we will be able to predict the exact time and place of the event itself is very variable. But certainly to predict risky areas and risky situations, it is possible.

Tait-Burkard agrees, saying: It is probably not all that easy to predict when the transmission is going to happen but what we can learn from this pandemic is to be better prepared. And we now have the facilities in place to do that preparedness, we will have to make sure there is money available to maintain these facilities.

This article first appeared in The Scotsmans Life Sciences 2021 supplement. A digital version can be found here.

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How experts have deployed data to tackle Covid-19 and plan for future pandemics - The Scotsman

Studies Reveal Designs of Nucleus and DNA – Discovery Institute

Image credit: Miroslaw Miras, via Pixabay.

You may have heard that all the DNA in your body, if stretched out, could reach to the Sun and back more than 70 times. What is even more amazing is that all this DNA occupies only a tiny fraction of the space within your body it is packed away inside the tiny nucleus of each cell. Furthermore, the DNA is not merely packed away and sitting idly; rather, it is a dynamic molecule taking part in several active processes including gene expression and cell division. Three new scientific papers have been published in recent weeks that reveal exquisite patterns of design in the DNA and nucleus in which it is housed.

The human genome is organized in 23 pairs of chromosomes. Most of the pairs are of similar length, but in the final 23rd pair, the first chromosome designated X is much longer than the second chromosome designated Y. That is not the only unique characteristic of the 23rd pair. These so-called sex chromosomes differ between the genders. While males have both an X and Y chromosome, females have two X chromosomes. As if to avoid a double dose of X chromosome genes, females inactivate one of their two X chromosomes during embryonic development. As for which of the two X chromosomes is inactivated, this appears to be done randomly in each cell. This means that females, unlike males, have two different functional genomes operating in their bodies, making for a fascinating twist to female genetics. That is, in some cells of the female, the first X chromosome is active whereas in the remainder of the cells the other X chromosome is active. A classic example is the colorful calico cat whose two X chromosomes code for two different colors.

Exactly how the developing female embryo inactivates one of the X chromosomes has not been well understood. What has been clear is that the story involves a region on the X chromosome itself, and information in that region that codes for a long RNA molecule, known as Xist. The name Xist stands forX-inactive specific transcript, a direct reference to its function of inactivating the X chromosome. But a genetic region that, ultimately, causes the inactivation of the entire chromosome must be handled very carefully. It is present on all X chromosomes but causes inactivation not of the single male X chromosome, and not of one of the two female X chromosomes. Importantly it causes inactivation only of the other female X chromosome.

In addition to the fact that Xist must be very carefully controlled, new research1is shedding light on how this single molecule can produce such a significant result. While it seemed that a very large number of Xist molecules must be required to inactivate the much larger X chromosome, the researchers studied mouse embryonic stem cells and found that only about one hundred Xists are required. The Xists, operating in pairs, recruit a large number of proteins. The result is about 50 complexes, each consisting of two Xists and an army of proteins, spaced along the X chromosome. Some of the proteins twist and condense the overall chromosome, compressing it so that most of the genes are close to one of the 50 complexes. Other proteins act to silence those nearby genes, thus essentially inactivating the entire X chromosome. Obviously, there are many important, coordinated, steps in this inactivation process, allowing for a small number of Xists to manage this big job. As the papers lead author remarked, It was kind of shocking to us that from just 50 sites, Xist manages to silence a thousand genes.2

X chromosome inactivation is not the only function that RNA molecules perform in the nucleus. They also, for example, help to maintain the overall three-dimensional structure of the various macromolecules in the nucleus, including the DNA. This is important because otherwise in the crowded nucleus, molecules can inadvertently chemically bond, or link, to one another. DNA crosslinking, for example, can result from environmental toxins and radiation. Such crosslinking, whether between DNA or other molecules, can cause cell death and is the goal in some chemotherapies. But crosslinking also is proving to be a valuable research tool. As another new paper reports,3crosslinking is now being used, along with several other complicated steps, to map out the three-dimensional structure of the DNA, various RNAs, and many proteins, within the nucleus. Simply put, the general idea is to link together molecules that are in close proximity. The cell is then broken down into clusters of linked molecules which can be identified and mapped out to reconstruct the structures within the nucleus.

The researchers found the certain RNA molecules serve to recruit and organize other RNA and protein molecules. Those recruited RNA and protein molecules, which otherwise would randomly move about, then serve important regulatory roles in accessing and processing the DNAs genetic information. The researchers also found that several high-concentration territories are formed within the nucleus, where these molecules cluster and function. As the paper explains, the organizing RNA molecules recruit diffusible RNA and protein regulators into precise 3D structures. What we are seeing is a much more detailed, elegant, and exacting picture of the nucleus than textbooks have ever envisioned.

The problem of organizing and maintaining the molecular structures within the nucleus becomes even more intriguing when one considers cellular division. When a cell divides, producing two daughter cells, the precise 3D nucleus structure discussed above must somehow be reestablished in the new cells. Certain proteins have been known to be important in this process, and another new study4has now identified a single protein that is particularly important in this cell division process. The protein, called lamin C, is, according to the paper, uniquely required for large-scale chromosome organization, and global 3D genome organization in the daughter cells.

During the process lamin C is phosphorylated, meaning a phosphoryl group is attached by special proteins. The phosphoryl group is removed when lamin C is done with its job, which is just one part of a larger, more complex process. As the lead researcher explained, There is this exquisite choreography of the different lamin proteins and DNA to get things just as they should be.5

Beyond this exquisite choreography, the crucial role of lamin C highlights another hallmark of design; namely, the teleology implicit when a part is required for its own production. Because lamin C, a protein, is produced by cellular protein synthesis. That is a process that begins with the genome in the nucleus, which is maintained by lamin C. In other words, lamin C is required for the production of lamin C.

These three studies of the structures within the cells nucleus continue to reveal a natural world that gives evidence design in many different ways.

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Studies Reveal Designs of Nucleus and DNA - Discovery Institute

Lost Women of Science, Episode 4: Breakfast in the Snow – Scientific American

From the COVID vaccine to pulsars to computer programming, women are at the source of many scientific discoveries, inventions and innovations that shape our lives. But in the stories weve come to accept about those breakthroughs, women are too often left out.

Each season at Lost Women of Science, well look at one woman and her scientific accomplishment: who she was, how she livedand what she found out. Katie Hafner, a longtime reporter for the New York Times, explains the science behind each womans work and explores the historical context in which she lived.

Our first season, The Pathologist in the Basement, is all about Dorothy Andersen, a physician and pathologist who solved a medical mystery when she identified and defined cystic fibrosis in 1938. A passionate outdoorswoman, a rugged individualist and a bit of an enigma, Andersen changed the way we understand acute lung and gastrointestinal problems in young children.

This podcast is distributed byPRXand published in partnership withScientific American.

Episode Transcript

FRANCIS COLLINS: [singing a capella] Dare to dream, dare to dream, all our brothers and sisters breathing free. Unafraid, our hopes unswayed, till the story of CF is history.

KATIE HAFNER: Im Katie Hafner and this is Lost Women of Science, a podcast in which we unearth stories of female scientists who didnt receive the recognition they deserved. We devote each season to the life and work of one woman. Were revisiting the historical record, one extraordinary scientist at a time.

This is the final episode of our first season, The Pathologist in the Basement. Weve been telling the story of Dr. Dorothy Andersen, a physician who was the first to identify the disease cystic fibrosis in the 1930s.

This episode is divided into two parts. One of those parts is linked to that voice you just heard singing. It belongs to Dr. Francis Collins, the outgoing director of the NIH. Dr. Collins is one of the geneticists who isolated the cystic fibrosis gene in 1989. In this episode, well explore advances in CF treatment. And well also explore Dorothy Andersens legacy, starting at the end of her life.

The last living keeper of that legacy is Dr. Celia Ores, a pediatrician mentored by Dr. Andersen in the early 1960s.

CELIA ORES: Can you put this down and we go and pick up Dr. Andersen and put her here on the table?

SOPHIE MCNULTY: Oh, the photo. Yeah. Yeah, let's go. Let's go find the photo.

MICHELLE ORES: I have it here, mom.

SOPHIE MCNULTY: Michelle has them.

CELIA ORES: Oh, okay.

MICHELLE ORES: I have the two photos. I have the one of Dorothy. And the one of you in Switzerland in medical school.

KATIE HAFNER: Were back in the New York apartment of Celia Ores.

Dr. Ores is now in her nineties. Shes holding a black-and-white photograph of Dr. Andersen close to her chest, as she talks to Sophie McNulty, our associate producer.

CELIA ORES: When I came to the United States, she was the only one who treated me really, really well.

KATIE HAFNER: Dorothy Andersen took Celia Ores under her wing, passing on what she had learned about cystic fibrosis, and in turn, Dr. Ores dedicated a large part of her career to patients with the disease.

CELIA ORES: Every little bit of cystic fibrosis that I know is what she told me. She told me everything.

If I had some issues with a patient that I don't fully understand, I went to her and told her that I don't know what I can do next for this patient.

KATIE HAFNER: But she couldnt help everyone. In the 1960s, cystic fibrosis patients rarely lived past their mid-teens.

But the story of cystic fibrosis takes a turn for the better.

And thats the heart of this episode: we believe Celia Ores is the only living person who actually knew Dorothy Andersen well, and in holding that photograph, shes holding Dr. Andersens legacy tight. In this episode, we want to tell you about that legacyand the progress that grew from her lifes work.

KATIE HAFNER: When she was working in the 1940s and 50s, Dorothy Andersen was driven to get the word out about what shed learned about cystic fibrosis. She went on lecture circuits, giving talks up and down the East Coast. When she was on vacation one summer in Europe -- or what she joked was a busmans holidayshe agreed to speak at medical schools and hospitals.

UNKNOWN: Dr. Andersen?

DOROTHY ANDERSEN: If you place a child with the celiac syndrome on a diet designed for celiac disease, you will find that most children with any form of failure to thrive will improve in weight somewhat.

KAITE HAFNER: It occurred to me while putting this season together that I didnt have a clue what Dr. Andersens spoken voice sounded like. But I was lying in bed one night, reading Scott Bairds biography of Dr. Andersen, and I noticed that he mentioned this, just in passing:

Her voice (from a professional recording in the late 1950s) was soft and musical.

I wrote to Scott immediately, and asked if he had the recording. He sent back an excerpt from a recording in which Dorothy Andersen and a few other physicians discuss the syndrome known as failure to thrive. Thats a catch-all term that was used to describe children who werent growing or gaining weight as quickly as they should.

UNKNOWN: Dr. Andersen, wed now like to hear what you have to say about the celiac syndrome, which includes cystic fibrosis and a variety of other conditions, some labeled as celiac disease.

DOROTHY ANDERSEN: The three characteristics of the celiac traid are failure to thrive, the passage of large, undigested stools, and an enlarged abdomen. The two most common diseases in this group are cystic fibrosis of the pancreas and gluten-induced celiac disease. Its fairly easy nowadays to sort out the cystic fibrosis cases from the rest by means of the sweat test.

KATIE HAFNER: Hearing her voice was a revelation. It was like hearing about someone for months then finally meeting them.

But despite all the work Dr. Andersen had done, at the end of the day, CF was still deadly and the stories of the patients were incredibly sadfor the families, of course, but also for the doctors.

CELIA ORES: Well, you go home and cried. It was very, very difficult for me to adjust to it. Because I would see young children that I tried to save from dying. And I didn't always succeed.

KATIE HAFNER: As a pediatrician in the 1960s, Celia Ores did all she could to extend the life of her patients. As did Dorothy Andersen.

CELIA ORES: It was a function to maintain the patient as best you can, as long as you can. And that's exactly what we were doing.

DORIS TULCIN: I knew Dorothy Anderson because she diagnosed my daughter who has cystic fibrosis.

KATIE HAFNER: Thats Doris Tulcin. You met her in episode one. Mrs. Tulcin took her daughter Ann to see Dr. Andersen in 1953, and she helped start the Cystic Fibrosis Foundation in the 1950s.

DORIS TULCIN: And I know that if she were alive today, she would be amazed at the journey that we've gone on for over 65 years.

KATIE HAFNER: Sadly, Dorothy Andersens own health took a nosedive in the early 1960s.

CELIA ORES: Every evening around four o'clock we would have some meeting. And there was five or six doctors, and some of the doctors she liked she would invite. So she would make some tea and we would talk about subjects such and such.

And one day she said in the evening, what are we going to talk about tonight? And the doctor, a male doctor, said, why don't we talk about Dorothys smoking? She said, You know, I like you very much. I think you're a very good doctor and you're a very nice human being, but if you behave like this, I will ask you not to come to our meetings.

[Sophie laughs]

SOPHIE MCNULTY: She was very tough?

CELIA ORES: Well, she didn't want to leave the smoking,

KATIE HAFNER: Research was starting to show that smoking was deadly.

AUDIO CLIP: The committee has reached the overall judgment that cigarette smoking is a health hazard of sufficient importance to the United States to warrant remedial action.

KATIE HAFNER: But many people in the 1950s and 60seven doctors, including Dorothy Andersenwere in denial. She was a lifelong chainsmoker. Almost everyone we spoke to about her mentioned itand this was all the more surprising since she spent so much of her professional life examining lungs that had become incapable of exchanging air.

Smoking eventually killed her.

Sophie McNulty: Do you remember the last time you saw her?

CELIA ORES: Yes. Uh, she was in a room alone and there was a sign, no, no entry, but she called me and I went to her to her to see her.

KATIE HAFNER: Dr. Andersen had always worked to protect Dr. Ores in an environment that was less than friendly to women.

CELIA ORES: And she said that she wanted to apologize to me that she didn't do more for me than she should have.

I told her that I lived under Hitler, I lived under Stalin, and I think I'll be able to survive the people in this unit. If I don't get as much in money or fame, that doesn't bother me.

It was very difficult because the women were considered for nothing.

KATIE HAFNER: Dorothy Hansine Andersen died on March 3, 1963. The cause was lung cancer. She was buried in Chicago alongside her parents.

SOPHIE MCNULTY: After she died, how did your work change?

CELIA ORES: I felt lonely in the hospital. I continued to take care of the children just as much as I did before, but it was... I didn't have anyone to discuss with the things that I discussed with her.

She was my guide. I could come to her and say, you know, such and such, that such and such, you know, I just felt comfortable when she was there.

KATIE HAFNER: After Dr. Andersens death, her farm in the Kittatinny mountains in New Jerseythe farm on which Dorothy Andersen built her cabin with her own hands, the farm where she invited colleagues and friends and put them to work chopping wood, and laying brick for the fireplace, the farm Celia Ores would visit with her childrenshe left that to close friends. Today, that land is a nature preserve.

Dorothy Andersen left her personal papers to Bessie Coombs Haskell.

Wait. Who?? We couldnt find much documentation of this friendship, except the brief mention of the bequest. But, according to people we called, Bessie was a friend of Dorothy Andersenor Andy as she was known to Bessie. Bessie Coombs Haskell ran a camp in St. George, Maine called the The Blueberry Cove Campand used to be a dancer in New Yorkbut we couldnt find much more than that.

Just what was the what, where, when and how of their friendship? What made Bessie Coombs Haskell so important in Dorothy Andersens life that she left her papers to this person, and not, say, to one of her friends in New Jersey, or to Celia Ores, or to another colleague at Columbia? It just goes to show you (and us) that there are many things we will never know about Dorothy Andersens life.

As far as we can tell, Bessie Coombs Haskell kept Dr. Andersens papers until she died. After that, its anybodys guess. We contacted the library in the small town of St. George on the coast of Maine, as well as the local museum and historical society. They had nothing. We did find Bessies grandson, who told us he was pretty sure he threw the papers away after his grandmother died.

At the end of the day, a legacy comes down to the stories people tell us, yes, but also to the things left behind. What gets kept and what gets thrown away. Its haphazard. Boxes get tossed in the trash. This is nobodys fault, but still, its profoundly disappointing.

Its profoundly disappointing because its not like Dorothy Andersen died in a previous millennium, in which case the lack of archival material would be totally understandable. But in the scheme of things, she died relatively recently.

So, one of the lessons I take from our dive into the life of Dorothy Andersen is this: if youre clearing out the basement or attic of a relative whos died, open the boxes. Dont throw out your grandmothers papers, because you just never know.

Coming up, the second part of this episode: Cystic fibrosis in the decades since Dorothy Andersens death. Im Katie Hafner and this is Lost Women of Science.

[AD BREAK]

KATIE HAFNER: Im Katie Hafner and this is Lost Women of Science: The Pathologist in the Basement.

Given all weve just said you might think the story ends with Dorothy Andersens death in 1963. But it doesnt. Her work has pioneered almost a century of science and discovery. To this day, Dorothy Andersens foundational research in cystic fibrosis continues to be built on. In the years since she died, the prognosis for CF patients has just gotten better and better and better.

Dr. William Skach is the outgoing chief scientific officer at the Cystic Fibrosis foundation. Hes been working on this disease for more than 30 years.

BILL SKACH: Well, in the 50s, the therapies were really incredibly simple and supportive.

It was recognized that the mucus in the lung was thick and couldn't be coughed out. So hydrating that mucus became one of the key goals. And, and patients used to sleep in mist tents because they thought that the breathing in the, the mist would then soften those secretions, which didn't really work very well.

Another problem at that time was antimicrobials, antibiotics, for, for the infections because the people with CF frequently got lung infections and that's really what caused most of the damage to the lungs, which was progressive, and, and eventually led to lung failure.

KATIE HAFNER: Parents were the lynchpin of the CF community. In the 1950s, with Doris Tulcin and a handful of others leading the way, parents banded together to form the Cystic Fibrosis Foundation. Today, the CF Foundation has a fund totaling more than $4.5 billion, which is about the same as the endowment of NYU.

BILL SKACH: And I will say that from its very beginning, it was really a collaborative effort with the community, with the scientists, with the physicians, to try to understand the disease better and to really work with the technology and the science at the time to take all of our understanding about the disease and turn it into therapies.

KATIE HAFNER: And it was during this period in the 50s, when Dr. Andersen was still at the forefront, that the focus was firmly on treating symptomsmaking CF patients as comfortable and functional as possible. But, as Dr. Skach points out:

BILL SKACH: With symptomatic therapy, you could only go so far. If you didn't really know what caused the disease, you couldn't really attack the basic root cause and reverse it. And so we got fairly good at treating the symptoms, but not good enough.

KATIE HAFNER: Children were still dying. The life expectancy had slowly been increasing over the years, but it was still devastatingly low.

For instance, in the 1980s, cystic fibrosis patients still werent expected to live much past their teens. Heres Brian OSullivan, the pediatric pulmonologist youve already met. Hes been working with CF patients for more than three decades.

BRIAN OSULLIVAN: And I do remember one family where the teenage girl was, was very sick, had been in the hospital for over two weeks, getting IV antibiotics, and and she had continued to deteriorate, um, and her parents knew she was dying and, and the parents actually came up to me and asked me to give their child permission to die, because they couldn't do it, but they knew she was hanging on just for them.

And so they left the room, I held her hand and told her that she had done everything she could do. She'd put up a great fight, but that she wasn't getting better.

And, uh, shortly thereafter she died, um, and her parents thanked me. Um, and that kind of experience doesn't leave you.

KATIE HAFNER: Around this time, scientists began redoubling their efforts in basic research, much of it funded by the Cystic Fibrosis foundation.

This takes us back to Francis Collinsthe outgoing director of the NIH. Back in the late 1980s, as a geneticist, he led a research team at the University of Michigan that was furiously searching for the CF gene, along with Lap-Chee Tsui, at the University of Toronto.

FRANCIS COLLINS: Lap-Chee and I met at a genetics conference in 1987. And it was clear we were all really struggling, trying to find what was quite literally, in my view, a needle in the haystack and the haystack was really big and the needle was hard to find. And we sat in the sun and talked about what each of our labs was doing as far as our approaches and realized that our approaches were not the same. They were actually beautifully complementary and we kind of decided on the spot and much credit to Lap-Chee, that he was willing to take this leap as well, that we would just merge our labs and we would stop competing. And we would basically become one family of researchers between Toronto and Ann Arbor.

And what seemed like it might be an unsolvable problem got solved in just about two years.

JANE GROGAN: Can you describe the moment when you and, and/or you and the team knew that you had the cystic fibrosis gene or the gene that causes cystic fibrosis?

KATIE HAFNER: Thats Jane Grogan, our scientist-in-residence. Shes an immunologist by training and currently running research in cell and gene therapy at GraphiteBio in San Francisco.

FRANCIS COLLINS: At the time I remember, uh, we were at a meeting. He and I were at Yale. It was one of those human genetics meetings and, uh, he had set up a fax machine in his room. We were all staying in the dorms at Yale, which were, shall we say a little austere.

And we had a very long day. And at the end of the day, he and I went to his room where the fax machine was. And there was all this paper on the floor. That's the way we communicated back then, there was no email.

JANE GROGAN: Some of us sending furious messages, right?

FRANCIS COLLINS: Yes! Cause it was that day's data. And so we pull the papers up off the floor and we began to look at the evidence that this three base pair deletion in a previously unknown gene correlated with cystic fibrosis and that as we looked through the data, it got better and better.

And that was it. That was it for me. That was a rainy night in May, 1989 in New Haven.

And I was like, over the moon, excited.

KATIE HAFNER: This discovery was a big big dealit was on the cover of the journal Science, and it was all over the popular press too. Now that the gene abnormality had been identified, it seemed that a cure for CF was just around the corner.

KATIE HAFNER: And the discovery of the gene has led to all kinds of things, right?

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Lost Women of Science, Episode 4: Breakfast in the Snow - Scientific American

What are the Trollocs in The Wheel of Time? Creatures origin explored – HITC

**Warning Spoilers ahead**

Sacrifice the mince pies this Christmas for a slice of Amazons The Wheel of Time. Up ahead, we explore the big bad enemies, the Trollocs, and where the creatures came from.

The Wheel of Time follows Rosamund Pikes wizard, Moiraine, who journeys across the lands in order to pinpoint who the reincarnation of the Dragon is and oversee their destiny to navigate the fate of the world.

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The Wheel of Time | Official Trailer | Amazon

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Trollocs are a species of Shadowspawn (creatures formed by the Dark One) created during the Age of Legends.

These creatures are known to have made up a large portion of the Dark Ones army and are a cross between humans and animal stock similar to Orcs.

Trollocs are able to communicate with the local tongue, however, their primitive side decreases their intelligence across the board, and therefore, they require supervision on the battlefield.

Similar to J. R. R. Tolkiens Uruk Hai, the antagonist during the War of the Shadow in The Wheel of Time, the Dark One, was hellbent on creating super soldiers for his army.

Using the skills of the Forsaken Aginor, human genetics were mixed with intelligent and sturdy animals, such as boars and eagles, to produce an advanced breed.

While early creations of the Trollocs were looked on as a failed experiment, the offspring of this new species eventually resulted in the birth of more sentient Trollocs known as the Myrddraal.

The Trollocs were introduced during the three-episode premiere of The Wheel of Time when Moiraine and Lan were ambushed.

Using a combination of Moiraines magical abilities and Lans swordsmanship to mitigate the Trollocs ambush, a telekinetic lightning storm was then produced.

The Trollocs arrival at the Two Rivers foreshadows a much larger threat looming and fans will have to wait and see the full force of the Dark One later on in season 1.

In other news, Release date for JoJos Bizarre Adventure Stone Ocean explained

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What are the Trollocs in The Wheel of Time? Creatures origin explored - HITC

I write while my children steal cars and rob houses: the awful human cost of racist stereotypes – The Guardian

As I write this article, my children are stealing cars and robbing houses, I suppose. I am an Indigenous father so, doesnt that tell you everything you need to know about me as a parent, and about my childrens capacity to understand right from wrong?

I know you sense the sarcasm in this. Well, a great, great majority of Australians would. But there is a certain type of person I am implicating here. The type who have an ignorance so deeply ingrained, that it is a wonder they havent wandered off into the dark recesses of our colonial history and followed each other off the edge of a cliff. Shouldnt they be extinct?

An article celebrating an infamous Bill Leak cartoon the one which depicts an Indigenous father unable to remember his childs name sparked me to respond to those with this mindset. I suggest you dont bother reading any of these articles dont give them the benefit of a click. But I will summarise: A journalist, hiding behind a rotting faade of caring about Indigenous children, argued that the statistics of Indigenous over-representation in prisons are caused by Indigenous parents [who] routinely abandon their responsibilities and do little to instil in their children respect for our laws and the property of others. According to this privileged white man, While [Indigenous parents] march up and down the street waving flags, their children are stealing cars, robbing houses and being hauled off to the watch-house.

The harm that racist comments and cartoons cause is never felt by those who make them. It is not white males, nor their children, who are creepily shadowed by security as they shop. They dont feel the suspicious glances that a First Nations father feels when he hugs his child, as if he is not a protector of the child, but as if the child needs protection from him. They would never have felt that thick and heavy fear that we feel, when we imagine what may well happen to our children should they step into the path of a cop who has nodded in agreement at a cartoon in a major paper, and believes that all Black kids, thanks to all Black parents, carry a greater criminal intent in our DNA.

Racist stereotypes have an awful human cost.

The fact that Indigenous people die around eight years younger than other Australians says more about how little regard our political system has for my people, than it does about our genetics. And the fact that Indigenous people are proportionately the most incarcerated people on the planet says more about our powerlessness as a people to hold the nations law and policymakers to account, than it does about my childrens capacity to understand right from wrong.

It really is as the Uluru Statement so eloquently and powerfully says:

Proportionately, we are the most incarcerated people on the planet. We are not an innately criminal people. Our children are aliened from their families at unprecedented rates. This cannot be because we have no love for them. And our youth languish in detention in obscene numbers. They should be our hope for the future. These dimensions of our crisis tell plainly the structural nature of our problem. This is the torment of our powerlessness.

And how can you argue with that, unless you believe we are less than human unless you are racist?

I had to think hard about if I bite back by writing this article. Why give the likes of Leak and others any attention, I wondered. Should I ignore it and focus on the positives rather than the negatives?

I concluded there should be a response. The stereotype must be defeated; not so much by changing the ignoramus mind, but by changing the country so the ignoramus is forced closer to that cliff.

And so it is to the pen, the ink, the keyboard we go, more and more Indigenous writers who are fighting fire with fire. We are the authors of who we are. Not old white men.

This is one of the reasons 12 First Nations men wrote a book with me, Dear Son Letters and reflections from First Nations fathers and sons. We wrote it, partly in response to publications like Bill Leaks racist cartoon, but also because of the awful legacies of the Northern Territory Intervention, and the crap we were taught about our First Nations forefathers in school that our forefathers were savages while the white students forefathers were our discoverers and saviours. Dear Son celebrates Indigenous fatherhood through letters and poems. We express love for ourselves and our families in a beautiful act of defiance.

The key factor is that contrary to claims of failed responsibility by Indigenous parents, we in fact are calling for greater responsibility. We march the streets and fly our flags, we protest because we love our children. We are calling to change this country for the better we want a referendum for a constitutionally enshrined Indigenous voice, so we may hold parliament accountable for failing to meet their responsibility to keep all Australians equally safe.

Thomas Mayor is a Kaurareg Aboriginal and Kalkalgal, Erubamle Torres Strait Islander. He is the Indigenous officer of the Maritime Union of Australia and the author of Dear Son Letters and reflections from First Nations fathers and sons. He tweets @tommayor11

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I write while my children steal cars and rob houses: the awful human cost of racist stereotypes - The Guardian

Treatment in Texas: For families of kids with rare diseases, its a full-time job to advocate for, raise millions for research – KXAN.com

AUSTIN (KXAN) How far would you go to save your childs life? Thats a question some parents have to ask themselves after learning their child has been diagnosed with a rare disease.

While each rare disease only impacts a small portion of the population, thousands of them exist. KXAN found many Texas parents are forced to quit their jobs and become full-time advocates for their kids after diagnosis. Funding research for potential treatments costs millions of dollars.

Here are some of those families.

Five-year-old Simon could probably hold his own against just about anyone in a game of Horse. Its something you would see go viral on social media, the little guy can sink baskets on his Little Tikes hoop for hours.

Simon loves basketball. His mom says hes been that way since he was 2 years old.

While his shooting is beyond impressive, its actually the happy dance he does when hes made a particularly impressive shot that might be more fun to watch. Its hard not to match Simons energy when youre in a room with him especially when hes sinking baskets one after another.

But this isnt what Simons life is going to look like much longer without treatment.

Simon has Sanfilippo Syndrome, a rare disease that his mom, Alina Gorniak, describes as Alzheimers in children. As the disease progresses, Simon will lose his ability to speak, care for himself, he wont be able to run or jump or shoot a basketball, hell suffer from seizures and by his teens, Simon will likely die.

I just cried and cried and cried, Gorniak said sitting on the floor with Simon in her lap, remembering the night she learned Simon had Sanfilippo. And then I woke up in the morning thinking okay, what do we do next?

The answer to that question was to fight, and parents like her have to if they want to see the needle move on potential treatments or cures for rare diseases. Because a rare disease, as the name indicates, impacts so few people proportionally, biotechnology companies dont generally initiate or fund the research.

Thats where the parents come in.

We have vulnerably opened our world up to the rest of the world in hopes of finding a cure for Simon and other kids with Sanfilippo Syndrome, Gorniak said.

Even though rare diseases are well, rare Simons family is far from alone. Maxwells family is going through a very similar process, trying to raise money for research that could potentially save their sons life.

Maxwell has a disease that doesnt even have a formal name, referred to by the gene SLC6A1. The disease causes developmental disabilities, a movement disorder and eventually debilitating epilepsy. Doctors told Maxwells parents that nothing could be done.

They said give him the best life you can, we have no idea what the future holds, youre going to become the expert in this disease,' Maxwells mom, Amber Freed, said.

Freed quit her job and started calling around to scientists and research groups hoping for a better answer. She found that UT Southwestern in Dallas was willing to develop a gene therapy that could potentially help Maxwell, and other kids with the same disease.

The catch, again, was money. Freed now works around the clock trying to raise enough of it to keep the research from being tabled.

By far the greatest challenge for me has been balancing motherhood while trying to help Maxwell. Its finding a balance between fighting for him and being with him, Freed said.

For these two families, its a full-time job seeking out groups and trials that could help their children. At the end of the day, Freed described her sons disease as one that fell into the too rare to care category.

Doctors are only going to see a couple of these cases in their lifetime, scientists dont work on them often and biotechs dont work on diseases that dont effect many people because its not profitable, Freed said.

UT Southwestern is where Maxwells family turned. Just this month, UT Southwestern was named a rare disease center for excellence by the National Organization for Rare Disorders (NORD). That designation is designed to help expand access, and advance care and research for rare disease patients in the United States, a news release said.

But to get her son connected to UT Southwestern, Freed says she had to send a researcher Uber Eats snacks with messages from Maxwell every day. Finally, she found he was going to be at a conference and just showed up.

Sat down right next to him in a row with no people in it and he turned to me and said hi, Amber,' Freed said. It was either going to be a beautiful team or he was going to file for a restraining order, and Im very happy to report that it has become a beautiful team.

Meanwhile, the Croke family turned to the Cure Sanfilippo Foundation. Glenn ONeill, the president of the foundation, also has a child with the syndrome Simon has. Like these families, he and his wife work full-time seeking out a cure.

Oftentimes its left to these parent foundations and organizations to make the difference, ONeill said.

The general rule of thumb is that to fund basic research, you need $100,000. To move that to a preclinical research stage, you need $1 million. To fund a phase one clinical trial youll need about $10 million and to get an approved treatment all the way through the FDA approval process costs between $50 and $100 million, ONeill told KXAN.

Were not going to sit back and do nothing, ONeill said. Were going to try and fund that early research so that it actually de-risks the research so biotechs are more interested because some of that early research has been done.

The National Organization for Rare Disorders puts out a report card every year, breaking down how all 50 states stack up when it comes to supporting people with rare diseases.

In their most recent report, published in January of 2021, Texas failed in three of the seven ranked categories. The state passed, or was given an A for three others.

You can read the report here:

There are more than 7,000 identified rare diseases, according to the National Institutes of Health (NIH). Roughly 95% of those diseases have no treatment.

Dr. Brendan Lee, professor and chairman of the department of molecular and human genetics at the Baylor College of Medicine, and the main investigator for the Undiagnosed Diseases Network, says theres just not enough research available to look into each and every rare disease.

There are so many rare diseases, and while theres enormous research that goes on in this country, in the world, and obviously the U.S. has been the leader in the world in investing in research and technology innovation, there still isnt enough research to account for every rare disease, Lee said.

The Undiagnosed Diseases Network works to help patients identify undiagnosed rare diseases and connects hospitals and researchers in an attempt to spread awareness and get people to solutions faster.

Patients often bounce around getting all different types of tests and they dont point to a known association, a label, Lee said. Thats where we and this network come together.

For more information about the UDN and the application process, visit the networks website.

Both of these Texas families need your help donating, and sharing their story.

The Freed family is working to raise $1 million to benefit SLC6A1 Connect, which is advocating for research to help find a treatment and cure for kids like Maxwell. To donate visit their GoFundMe here.

Gorniak and her husband working to raise $1 million for the Cure Sanfilippo Foundation, which is doing research that could help kids like Simon. A fundraiser for the Cure Sanfilippo Foundation through Simons family can be found on GoFundMe.

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Treatment in Texas: For families of kids with rare diseases, its a full-time job to advocate for, raise millions for research - KXAN.com

Human evolutionary genetics – Wikipedia

study of differences between human genomes

Human evolutionary genetics studies how one human genome differs from another human genome, the evolutionary past that gave rise to the human genome, and its current effects. Differences between genomes have anthropological, medical, historical and forensic implications and applications. Genetic data can provide important insights into human evolution.

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Biologists classify humans, along with only a few other species, as great apes (species in the family Hominidae). The living Hominidae include two distinct species of chimpanzee (the bonobo, Pan paniscus, and the common chimpanzee, Pan troglodytes), two species of gorilla (the western gorilla, Gorilla gorilla, and the eastern gorilla, Gorilla graueri), and two species of orangutan (the Bornean orangutan, Pongo pygmaeus, and the Sumatran orangutan, Pongo abelii). The great apes with the family Hylobatidae of gibbons form the superfamily Hominoidea of apes.

Apes, in turn, belong to the primate order (>400 species), along with the Old World monkeys, the New World monkeys, and others. Data from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) indicate that primates belong to the group of Euarchontoglires, together with Rodentia, Lagomorpha, Dermoptera, and Scandentia.[1] This is further supported by Alu-like short interspersed nuclear elements (SINEs) which have been found only in members of the Euarchontoglires.[2]

A phylogenetic tree is usually derived from DNA or protein sequences from populations. Often, mitochondrial DNA or Y chromosome sequences are used to study ancient human demographics. These single-locus sources of DNA do not recombine and are almost always inherited from a single parent, with only one known exception in mtDNA.[3] Individuals from closer geographic regions generally tend to be more similar than individuals from regions farther away. Distance on a phylogenetic tree can be used approximately to indicate:

The separation of humans from their closest relatives, the non-human apes (chimpanzees and gorillas), has been studied extensively for more than a century. Five major questions have been addressed:

As discussed before, different parts of the genome show different sequence divergence between different hominoids. It has also been shown that the sequence divergence between DNA from humans and chimpanzees varies greatly. For example, the sequence divergence varies between 0% to 2.66% between non-coding, non-repetitive genomic regions of humans and chimpanzees.[8] The percentage of nucleotides in the human genome (hg38) that had one-to-one exact matches in the chimpanzee genome (pantro6) was 84.38%. Additionally gene trees, generated by comparative analysis of DNA segments, do not always fit the species tree. Summing up:

The divergence time of humans from other apes is of great interest. One of the first molecular studies, published in 1967 measured immunological distances (IDs) between different primates.[10] Basically the study measured the strength of immunological response that an antigen from one species (human albumin) induces in the immune system of another species (human, chimpanzee, gorilla and Old World monkeys). Closely related species should have similar antigens and therefore weaker immunological response to each other's antigens. The immunological response of a species to its own antigens (e.g. human to human) was set to be 1.

The ID between humans and gorillas was determined to be 1.09, that between humans and chimpanzees was determined as 1.14. However the distance to six different Old World monkeys was on average 2.46, indicating that the African apes are more closely related to humans than to monkeys. The authors consider the divergence time between Old World monkeys and hominoids to be 30 million years ago (MYA), based on fossil data, and the immunological distance was considered to grow at a constant rate. They concluded that divergence time of humans and the African apes to be roughly ~5 MYA. That was a surprising result. Most scientists at that time thought that humans and great apes diverged much earlier (>15 MYA).

The gorilla was, in ID terms, closer to human than to chimpanzees; however, the difference was so slight that the trichotomy could not be resolved with certainty. Later studies based on molecular genetics were able to resolve the trichotomy: chimpanzees are phylogenetically closer to humans than to gorillas. However, some divergence times estimated later (using much more sophisticated methods in molecular genetics) do not substantially differ from the very first estimate in 1967, but a recent paper[11] puts it at 1114 MYA.

Current methods to determine divergence times use DNA sequence alignments and molecular clocks. Usually the molecular clock is calibrated assuming that the orangutan split from the African apes (including humans) 12-16 MYA. Some studies also include some old world monkeys and set the divergence time of them from hominoids to 25-30 MYA. Both calibration points are based on very little fossil data and have been criticized.[12]

If these dates are revised, the divergence times estimated from molecular data will change as well. However, the relative divergence times are unlikely to change. Even if we can't tell absolute divergence times exactly, we can be pretty sure that the divergence time between chimpanzees and humans is about sixfold shorter than between chimpanzees (or humans) and monkeys.

One study (Takahata et al., 1995) used 15 DNA sequences from different regions of the genome from human and chimpanzee and 7 DNA sequences from human, chimpanzee and gorilla.[13] They determined that chimpanzees are more closely related to humans than gorillas. Using various statistical methods, they estimated the divergence time human-chimp to be 4.7 MYA and the divergence time between gorillas and humans (and chimps) to be 7.2 MYA.

Additionally they estimated the effective population size of the common ancestor of humans and chimpanzees to be ~100,000. This was somewhat surprising since the present day effective population size of humans is estimated to be only ~10,000. If true that means that the human lineage would have experienced an immense decrease of its effective population size (and thus genetic diversity) in its evolution. (see Toba catastrophe theory)

Another study (Chen & Li, 2001) sequenced 53 non-repetitive, intergenic DNA segments from human, chimpanzee, gorilla and orangutan.[8] When the DNA sequences were concatenated to a single long sequence, the generated neighbor-joining tree supported the Homo-Pan clade with 100% bootstrap (that is that humans and chimpanzees are the closest related species of the four). When three species are fairly closely related to each other (like human, chimpanzee and gorilla), the trees obtained from DNA sequence data may not be congruent with the tree that represents the speciation (species tree).

The shorter internodal time span (TIN) the more common are incongruent gene trees. The effective population size (Ne) of the internodal population determines how long genetic lineages are preserved in the population. A higher effective population size causes more incongruent gene trees. Therefore, if the internodal time span is known, the ancestral effective population size of the common ancestor of humans and chimpanzees can be calculated.

When each segment was analyzed individually, 31 supported the Homo-Pan clade, 10 supported the Homo-Gorilla clade, and 12 supported the Pan-Gorilla clade. Using the molecular clock the authors estimated that gorillas split up first 6.2-8.4 MYA and chimpanzees and humans split up 1.6-2.2 million years later (internodal time span) 4.6-6.2 MYA. The internodal time span is useful to estimate the ancestral effective population size of the common ancestor of humans and chimpanzees.

A parsimonious analysis revealed that 24 loci supported the Homo-Pan clade, 7 supported the Homo-Gorilla clade, 2 supported the Pan-Gorilla clade and 20 gave no resolution. Additionally they took 35 protein coding loci from databases. Of these 12 supported the Homo-Pan clade, 3 the Homo-Gorilla clade, 4 the Pan-Gorilla clade and 16 gave no resolution. Therefore, only ~70% of the 52 loci that gave a resolution (33 intergenic, 19 protein coding) support the 'correct' species tree. From the fraction of loci which did not support the species tree and the internodal time span they estimated previously, the effective population of the common ancestor of humans and chimpanzees was estimated to be ~52 000 to 96 000. This value is not as high as that from the first study (Takahata), but still much higher than present day effective population size of humans.

A third study (Yang, 2002) used the same dataset that Chen and Li used but estimated the ancestral effective population of 'only' ~12,000 to 21,000, using a different statistical method.[14]

The alignable sequences within genomes of humans and chimpanzees differ by about 35 million single-nucleotide substitutions. Additionally about 3% of the complete genomes differ by deletions, insertions and duplications.[15]

Since mutation rate is relatively constant, roughly one half of these changes occurred in the human lineage. Only a very tiny fraction of those fixed differences gave rise to the different phenotypes of humans and chimpanzees and finding those is a great challenge. The vast majority of the differences are neutral and do not affect the phenotype.[citation needed]

Molecular evolution may act in different ways, through protein evolution, gene loss, differential gene regulation and RNA evolution. All are thought to have played some part in human evolution.

Many different mutations can inactivate a gene, but few will change its function in a specific way. Inactivation mutations will therefore be readily available for selection to act on. Gene loss could thus be a common mechanism of evolutionary adaptation (the "less-is-more" hypothesis).[16]

80 genes were lost in the human lineage after separation from the last common ancestor with the chimpanzee. 36 of those were for olfactory receptors. Genes involved in chemoreception and immune response are overrepresented.[17] Another study estimated that 86 genes had been lost.[18]

A gene for type I hair keratin was lost in the human lineage. Keratins are a major component of hairs. Humans still have nine functional type I hair keratin genes, but the loss of that particular gene may have caused the thinning of human body hair. Based on the assumption of a constant molecular clock, the study predicts the gene loss occurred relatively recently in human evolutionless than 240 000 years ago, but both the Vindija Neandertal and the high-coverage Denisovan sequence contain the same premature stop codons as modern humans and hence dating should be greater than 750 000 years ago. [19]

Stedman et al. (2004) stated that the loss of the sarcomeric myosin gene MYH16 in the human lineage led to smaller masticatory muscles. They estimated that the mutation that led to the inactivation (a two base pair deletion) occurred 2.4 million years ago, predating the appearance of Homo ergaster/erectus in Africa. The period that followed was marked by a strong increase in cranial capacity, promoting speculation that the loss of the gene may have removed an evolutionary constraint on brain size in the genus Homo.[20]

Another estimate for the loss of the MYH16 gene is 5.3 million years ago, long before Homo appeared.[21]

Segmental duplications (SDs or LCRs) have had roles in creating new primate genes and shaping human genetic variation.

When the human genome was compared to the genomes of five comparison primate species, including the chimpanzee, gorilla, orangutan, gibbon, and macaque, it was found that there are approximately 20,000 human-specific insertions believed to be regulatory. While most insertions appear to be fitness neutral, a small amount have been identified in positively selected genes showing associations to neural phenotypes and some relating to dental and sensory perception-related phenotypes. These findings hint at the seemingly important role of human-specific insertions in the recent evolution of humans.[22]

Human accelerated regions are areas of the genome that differ between humans and chimpanzees to a greater extent than can be explained by genetic drift over the time since the two species shared a common ancestor. These regions show signs of being subject to natural selection, leading to the evolution of distinctly human traits. Two examples are HAR1F, which is believed to be related to brain development and HAR2 (a.k.a. HACNS1) that may have played a role in the development of the opposable thumb.

It has also been hypothesized that much of the difference between humans and chimpanzees is attributable to the regulation of gene expression rather than differences in the genes themselves. Analyses of conserved non-coding sequences, which often contain functional and thus positively selected regulatory regions, address this possibility.[23]

When the draft sequence of the common chimpanzee (Pan troglodytes) genome was published in the summer 2005, 2400 million bases (of ~3160 million bases) were sequenced and assembled well enough to be compared to the human genome.[15] 1.23% of this sequenced differed by single-base substitutions. Of this, 1.06% or less was thought to represent fixed differences between the species, with the rest being variant sites in humans or chimpanzees. Another type of difference, called indels (insertions/deletions) accounted for many fewer differences (15% as many), but contributed ~1.5% of unique sequence to each genome, since each insertion or deletion can involve anywhere from one base to millions of bases.[15]

A companion paper examined segmental duplications in the two genomes,[24] whose insertion and deletion into the genome account for much of the indel sequence. They found that a total of 2.7% of euchromatic sequence had been differentially duplicated in one or the other lineage.

The sequence divergence has generally the following pattern: Human-Chimp < Human-Gorilla << Human-Orangutan, highlighting the close kinship between humans and the African apes. Alu elements diverge quickly due to their high frequency of CpG dinucleotides which mutate roughly 10 times more often than the average nucleotide in the genome. The mutation rate is higher in the male germ line, therefore the divergence in the Y chromosomewhich is inherited solely from the fatheris higher than in autosomes. The X chromosome is inherited twice as often through the female germ line as through the male germ line and therefore shows slightly lower sequence divergence. The sequence divergence of the Xq13.3 region is surprisingly low between humans and chimpanzees.[25]

Mutations altering the amino acid sequence of proteins (Ka) are the least common. In fact ~29% of all orthologous proteins are identical between human and chimpanzee. The typical protein differs by only two amino acids.[15]The measures of sequence divergence shown in the table only take the substitutional differences, for example from an A (adenine) to a G (guanine), into account. DNA sequences may however also differ by insertions and deletions (indels) of bases. These are usually stripped from the alignments before the calculation of sequence divergence is performed.

An international group of scientists completed a draft sequence of the Neanderthal genome in May 2010. The results indicate some breeding between modern humans (Homo sapiens) and Neanderthals (Homo neanderthalensis), as the genomes of non-African humans have 14% more in common with Neanderthals than do the genomes of subsaharan Africans. Neanderthals and most modern humans share a lactose-intolerant variant of the lactase gene that encodes an enzyme that is unable to break down lactose in milk after weaning. Modern humans and Neanderthals also share the FOXP2 gene variant associated with brain development and with speech in modern humans, indicating that Neanderthals may have been able to speak. Chimps have two amino acid differences in FOXP2 compared with human and Neanderthal FOXP2.[26][27][28]

H. sapiens is thought to have emerged about 300,000 years ago. It dispersed throughout Africa, and after 70,000 years ago throughout Eurasia and Oceania.A 2009 study identified 14 "ancestral population clusters", the most remote being the San people of Southern Africa.[29][30]

With their rapid expansion throughout different climate zones, and especially with the availability of new food sources with the domestication of cattle and the development of agriculture, human populations have been exposed to significant selective pressures since their dispersal. For example, East Asians have been found to be separated from Europids by a number of concentrated alleles suggestive of selection pressures, including variants of the EDAR, ADH1B, ABCC1, and ALDH2genes.The East Asian types of ADH1B in particular are associated with rice domestication and would thus have arisen after the development of rice cultivation roughly 10,000 years ago.[31] Several phenotypical traits of characteristic of East Asians are due to a single mutation of the EDAR gene, dated to c. 35,000 years ago.[32]

As of 2017[update], the Single Nucleotide Polymorphism Database (dbSNP), which lists SNP and other variants, listed a total of 324 million variants found in sequenced human genomes.[33]Nucleotide diversity, the average proportion of nucleotides that differ between two individuals, is estimated at between 0.1% and 0.4% for contemporary humans (compared to 2% between humans and chimpanzees).[34][35]This corresponds to genome differences at a few million sites; the 1000 Genomes Project similarly found that "a typical [individual] genome differs from the reference human genome at 4.1 million to 5.0 million sites affecting 20 million bases of sequence."[36]

In February 2019, scientists discovered evidence, based on genetics studies using artificial intelligence (AI), that suggest the existence of an unknown human ancestor species, not Neanderthal, Denisovan or human hybrid (like Denny (hybrid hominin)), in the genome of modern humans.[37][38]

In March 2019, Chinese scientists reported inserting the human brain-related MCPH1 gene into laboratory rhesus monkeys, resulting in the transgenic monkeys performing better and answering faster on "short-term memory tests involving matching colors and shapes", compared to control non-transgenic monkeys, according to the researchers.[39][40]

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Human evolutionary genetics - Wikipedia

The pillage people: Gene scientists working to crack the Norse code find Scots Vikings all around the globe – The Sunday Post

They sailed the treacherous North Sea in their longboats to reach Scotlands most northern shorelines where the pillaging and settling meant many islanders have a little Viking blood.

Now 1,400 years later their descendants have continued that tradition of intrepid voyage, settling in far flung parts of the world and taking their Norse and Scottish genes with them.

Just how far that gene pool has spread is the unexpected discovery of a major scientific study which is using people whose ancestry stretches back to Scotlands Northern Isles to improve the understanding of major diseases.

When researchers from Edinburgh University asked people with two grandparents from the islands to get in touch for the study, they got replies from as far away as New Zealand, the Canadian Rockies and even Honolulu, Hawaii.

The study, called Viking II, by Jim Wilson, professor of human genetics at Edinburgh Universitys Centre for Global Health Research, is examining the genetic variants in Orkney and Shetland descendants to unlock the mystery of diseases including cancer, heart disease and MS.

The research follows the original Viking Health Study which recruited 2,000 people with at least two grandparents from Orkney, and 2,000 with the same link to Shetland. Now another 4,000 are being enlisted, to bring the total to 8,000. It will allow professor Wilsons team to further develop its research into these major diseases.

He said: We need to look at 4,000 folk who have two grandparents born on the islands. Our global appeal for the grandchildren of at least two Orkney or Shetland grandparents has had a response from more than 3,000 people from places like Canada, Honolulu, South Africa and New Zealand, as well as nearer to home, in Scotland.

Its wonderful to see how far they travelled but each one of them is vital to our research.

People taking part in the study are asked to answer a questionnaire, and also to send a sample of saliva. Orkney and Shetland are the most genetically distinct populations in the whole of Britain and Ireland.

Professor Wilson has previously found that most islanders DNA is predominantly Scottish, but with about 20% traceable to Norwegian ancestors.

He said: We are trying to understand the genetic contribution to cancer and heart conditions by looking at the distinct genetic variant present in their gene pools.

By using distinct or specific gene pools we can look closely at a population to see which inherited health issues go down the generations. Initial evidence shows that some heart anomalies are more common as is a type of cancer caused by the BRCA type 1 gene.

We already know that multiple sclerosis is more common on Orkney. Genetically, I am part Norwegian and part Pictish, the indigenous Scots who clashed with Roman legions as they moved north. My father was from the Fair Isle.

The obvious conclusion is to see the potential of screening for those diseases and head them off at the pass, so to speak.

One of the survey volunteers is former Canadian army munitions expert Douglas Loader, who lives near the Rocky Mountains.

His mother was born and raised on Orkney before working in the British Embassy in Moscow. It was there she met his father, who worked at the Canadian embassy, and they both settled in Canada.

Douglas, 50, from Medicine Hat, Alberta, said: My mother Elizabeth Corse was born in Kirkwall and developed breast cancer and I have prostate cancer which I am told is a related one and is being studied in Viking II. I have always seen myself as Orkney island diaspora but never thought I would ever make a contribution to scientific research.

You can travel thousands of miles and generations from your origins, but your genes will always journey with you.

You will find that there are many of us scattered over the world.

Orkney and Shetland were owned by Norway until 1468 until it was given as a dowry for the Norwegian Queen Margaret, when she married James III of Scotland.

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The pillage people: Gene scientists working to crack the Norse code find Scots Vikings all around the globe - The Sunday Post

The future is here, where are we in Jammu and Kashmir? – Daily Excelsior

PRECISION GENOMICS

Dr. Swarkar SharmaDeoxyribonucleic Acid (DNA) constitutes genome, contains biological instructions to make each species unique and along with the instructions it contains, is inherited from one generation to next generation. This biological information is encoded in fragments of DNA called Genes. To keep things simple in understanding, there are approximately 20,000-25,000 Genes in humans. These individually or in combinations/associations with other regions of genome, as well as interactions with environment, take care of composition and all the functions of the body. Each Gene has primarily two copies and Mother and Father contribute equally, one copy each, that they have inherited from their parents. In this way, transmission of characters from parents to children is controlled (known as heredity). During course of inheritance as well as growth of a body, due to various factors, some changes may arise in DNA and are called mutation or variations. Some of these variations remain restricted to the individual itself (somatic) or are inherited to the next generation (Germline). These variations can be neutral or may have negative or positive impact as they may affect function of a Gene. In addition, as genes have potential to interact with environmental conditions, these variations may effect function of a gene and subsequently expression of the characteristics. When a positive effect, it can be beneficial by helping in adaptation to environment and better survival. However, if negative impact, may result in a disease condition. With this background, to summarize, DNA and its composition may play critical role in defining physical features (called phenotypes), disease predisposition (susceptibility) or resulting in genetic disorder condition, based on how strong the effect of variation is (called penetrance). Thus, this spectrum, like rare monogenic (single gene caused) diseases to complex multifactorial and polygenic (multiple genes and environment) characteristics/disorders, clearly depends on penetrance of these variations.With the exponential development in genomic approaches and advent of Next Generation Sequencing (NGS) and high end computational data analyses (big data in genomics), that has already facilitated screening of whole genome of an Individual in couple of hours itself, new domain in healthcare, Precision Medicine is emerging. With continuous improvement in the methodologies and, development and establishment of baseline datasets, in developed countries it has already secured its place in healthcare in various domains. In India, it is slowly making its way, primarily in Tier 1 cities. Precision Genomics offers healthcare providers important genomic information that can help personalize ones treatment, determine ones risk for certain genetic conditions, and even identify how well one may respond to certain medications and dosages. This helps reduce costs while providing a better experience overall. In addition, it has been observed that incorporation of genomics in healthcare, especially to address rare genetic conditions, has facilitated beyond limits in characterization, identification and therapeutic intervention.It is important to mention that scientific evidences suggest that Indian populations have unique genepool that it has acquired over period of time due to different population specific natural selection scenarios and migrations etc. Over the period of time, due to our social practices, it may have resulted in unique population specific genetic signatures, many of which may be restricted to independent population groups (endogroups: based on religion, caste, language, ethnicity etc.). With upcoming research in the domain, these are being explored and many a such signatures are coming into light. Yet, a lot has to be done keeping in mind huge population diversity of the land and extensive geographical and social distribution of various endogroups countrywide.The population structure of Jammu and Kashmir is also quite unique. J&K is mainly a hilly terrain, so majority of the population groups exist in small geographic pockets throughout the region and until recently these population groups have remained isolated which might have resulted in diverse but conserved gene pool over a period of time, as observed by various studies carried out by our research group. Subsequently, the health hazards and diseases in the region that affect the populations in the region, in addition to the common ones, hugely are different rare disorders, many remain uncharacterized, may be restricted to particular families or populations, yet to be understood and gain attention. In many of such disorders, that are not lethal in early age, individuals remain normal at birth and have disease symptoms later in age that keep on intensifying with advancement of age, sometimes resulting in loss of life. To highlight, geographic isolation and most of the population groups practicing and performing marriages preferentially within particular subgroups, result in high inbreeding. Adding to it, majority of population of Jammu and Kashmir practice consanguinity (i.e. marriage with in the family). It is a known fact that high consanguinity cause high incidence of rare genetic disorders. In light of such population structure in J&K, a high incidence of rare genetic disorders is expected in the region, to the extent, these rare disorders start to appear like an epidemic in isolated areas. Carrying this information to general public is an important component in the maintenance and control of such disorders. It is need of the day that not only population residing in urban areas but remote areas too are educated about genetic disorders as well as practice of high consanguinity especially, in situations when incidence of disorders is reported in families.With this background, Human Genetics Research Group at School of Biotechnology at Shri Mata Vaishno Devi University, Katra, with support from collaborators, has initiated a project called Project JK-DNA. The purpose of the project is to provide an online open access resource with the goal of aggregating and harmonising both Human Exome and Genome sequencing data from population of J&K through its genome sequencing projects (Next Generation Sequencing), published resources or public datasets, and making summary data available for the use of wider scientific community especially medical researchers in J&K and India. HGRG SMVDU has plans to pool NGS datasets, generated with collaborators from Institute of Human Genetics and School of Biotechnology, University of Jammu for better and higher genomic resolution. The portal will also feature various scientific outcomes in the domain, from the region, in simple and laymans terms for the knowledge and awareness of common masses. The project is powered through a J&K startup Biodroid Innovations Pvt ltd and the product series Key2genes.For more details visit http://WWW.JKDNA.IN : The online portal to help understand the genetic makeup of Human Population of Jammu and KashmirAbout HGRG:Human Genetics Research Group (HGRG) is established at School of Biotechnology, Shri Mata Vaishno Devi University Katra, Jammu and Kashmir, India. HGRG team, comprised of researchers with enhanced skill sets, is working in the area Human Evolutionary Genetics, Rare Undiagnosed Genetic Disorders and Complex Genetic disorders in Human population of Jammu and Kashmir. The group has received research grants from various external Funding agencies: DST SERB GoI; UGC GoI, CSIR GoI; National Geographic Society, USA. Group has high impact scientific research publications and patents to their credit.

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The future is here, where are we in Jammu and Kashmir? - Daily Excelsior

Model organisms are more than just monkeys and mice – DW (English)

Model organisms or research organisms, as they are also known are living things that scientists, such as biologists, use to study human and other animal or plant life.

A model organism can be anything from single-celled bacteria to viruses and fungi. They can be more complex organisms, such as monkeys, mice, rats, frogs, elephants and a salamandercalled axolotl.

Monkeys and mice are considered incredibly important for the study of human disease and ageing, because they are genetically so similar to humans. And research on primates and rodents has led to some major scientific breakthroughs.

Illustration by Per Sander

The field is not without its opponents, though, and let's not mince our words its downsides.

One of the most basic scientific and ethical questions asks whether it's okay to subject non-human animals to experimental pain in a laboratory when we wouldn't do that with humans.

Think of vaccines and other medicines: Before they get tested on people, they are tested on non-human animals to look for dangerous side-effects.

Even further down the track, in human clinical trials, people can have extreme and adverse reactions to a drug in development. And that's when the drug has been somewhat refined to limit negative outcomes.

Illustration by Simone Hls

But with monkeys and rats, is it okay to just go ahead and test potentially lethal chemicals? Or what of psychological trials, like studying pain stimuli on mice? Is that okay? Does that mean that a monkey's life is worth less than a human life?

There are regulations to ensure the welfare of animals in research and, increasingly, some technical alternatives, such as computing models that use artificial intelligence and machine learning systems.

They can calculate what may happen if you put a medicinal compound in a body. But you can't avoid testing medicines on animals, including humans, in the end. How else would you know whether there are any benefits for human life?

Illustration by Simone Hls

There are less controversial model organisms than monkeys unexpected yet common things such as tomatoes, fruit flies, worms, and other vegetation. The axolotl is especially interesting because it keeps it's tadpole-like juvenile characteristics into adulthood. This includesexternalgills. But it is not a fish, it's a salamander.

One such plant is even celebrating the 200th anniversary of its naming, or to be precise, its renaming, and that's Arabidopsis thaliana.

A Swiss botanist called A.P. de Candolle coined the term Arabidopsis to describe a group of Brassicaceae plants in the mustard family in 1821.

In a paper published in the Journal of Plant Biochemistry and Biotechnology, Rajnish Khana and Ulrich Kutschera explain how a German botanist, Friedrich Laibach, then "established the mustard plant A. thaliana (L.) Heynh as a model organism in plant genetics []."

It has since become integral to stem cell research and is still delivering insights.

Illustration by Barbara Scheid

Khana and Kutschera write that A. thaliana is an ideal model organism for some very basic reasons: it's small and easy to grow, it has a short generation time the average time from the birth of one living thing to the birth of its offspring it produces up to 10,000 seeds per plant, and it's easy to manipulate and mutate.

Model organisms are categorized into various groups. The categories start with viruses, such as Phage lambda and the Tobacco mosaic virus.

Illustration by Christian Kuhn

The Lambda phage, for instance, is what's known as a temperate virus, which infects host bacteria, such as E.coli.

Being temperate, Phage lambda has different ways of infecting a cell, but it has to decide which it wants to use. And it's that decision-making process at such a fundamental level of life that has intrigued scientists. Studying the process allows them to learn about our own biological development.

Some researchers say it's important to continue studying viruses on the brink of global eradication, such as polio.

Even viruses such as Ebola, Zika and influenza can be used as model organisms to teach us about genetic and hereditary processes in RNA, the messengers of DNA the thing that makes living things unique individuals.

The next category is Prokaryotes. A prokaryote is any organism that lacks a distinct nucleus, the thing that controls the activity of a cell.

Illustration by Barbara Scheid

The most common prokaryotes are bacteria, such as E.coli (Escherichia coli), which is used to study molecular genetics. Synechocystis is a bacterium that is commonly used to research photosynthesis.

Next on the list and arguably the largest and best-known group involves eukaryotes. Eukaryotes are cells or organisms that are thought to have evolved about 2 billion years ago.

Compared to prokaryotes, eukaryotes have a clearly defined nucleus.

They include protists. Protists are often but not exclusively microscopic, single-celled organisms.

Illustration by Christian Kuhn

Eukaryotes also include fungi. There's Neurospora crassa, an orange bread mold, for instance, that's been used to study metabolic regulation and the circadian rhythm the latter being a field that won a Nobel Prize only a few years ago.

Baker's yeast is used in genetic research, as are Coprinus cinereus mushrooms. They have been useful in the study of meiosis, or cell-division, which is important for understanding reproduction.

Arabidopsis thaliana, mentioned above, is also a eukaryote. It belongs to a group of so-called higher plants.

Illustration by Peter Steinmetz

Then there are animals, both invertebrate and vertebrate.

Let's start with invertebrate animals. The US National Wildlife Federation describes invertebrates as the "most diverse and numerous group of animals on Earth."

Invertebrates have no spine. They can live on land or in water.

Illustration by Simone Hls

So, they include animals such as the common fruit fly and hydra, an aquatic animal.

Many have been used in molecular biology or biomedical experiments.

And last, but by no means least, we have the vertebrates arguably, the most controversial group of model organisms.

Vertebrates are defined by their having a spine.

Illustration by Olof Pock

Now, if you wanted to be cynical, you may like to suggest that some vertebrates have more of a spine than others. We humans, for instance, could be accused of being spineless for willingly subjecting other animals to pain that we would rather not endure ourselves. But that argument is up for grabs.

The usual suspects among the vertebrate model organisms are the aforementioned monkeys, rats and mice. But they also include dogs, frogs, chickens and cats, and birds used to study communication among songbirds and non-mammalian auditory systems.

Then there's the beautiful zebrafish, a freshwater tropical specimen.

Zebrafish are virtually transparent. That offers scientists with an almost unique view of an animal's internal anatomy.

Illustration by Simone Hls

But if that's not cool enough, Zebrafish are becoming more and more attractive as a model organism because about 70% of their genes are similar to human genes.

They also have similar bodily components or organs. Zebrafish have two eyes, a mouth, a brain, intestine, pancreas, liver, bile ducts, kidney, a heart, ears, nose, cartilage, and teeth just like humans.

Researchers says it's therefore possible to use zebrafish to model and study genetic changes, which in humans would lead to disease.

That's also one reason why some researchers say zebrafish are becoming more popular in the lab than mice.

Illustration by Simone Hls

Mice are not to be discounted, however. German scientists recently reported that they had cured mice of paralysis after the animals had suffered a spinal cord injury.

But the use of animals, especially those so genetically close to humans, with all the scientific benefits for human life, remains contentious for both scientists and observers of research that uses mammalian model organisms.

Germany's Max-Planck Society writes that "monkeys are used in animal research only if a particular phenomenon cannot be studied on any other species of animal, such as mice, fish or fruit flies. [] They are used primarily for the final drug safety tests on new medicines before they are used on humans."

That is one perspective. Elsewhere, scientists are moving from mice to monkeys.

Illustration by Benjamin St

A feature article in Nature has suggested that cynomolgus macaque monkeys (also known as long-tailed or crab-eating macaques) may be the focus of a "new era of animal models for autism and other brain and psychiatric diseases."

Macaques are already among the most commonly used non-human primates in biomedical research.

The RSPCA, an animal welfare charity in the UK, saysprimates are "highly intelligent animals [] that suffer in similar ways to us."

It goes on to say that "the capture of wild primates for use in breeding colonies and for experiments in some countries causes very significant suffering we believe this is completely unacceptable."I

llustrations by Simone Hls, Christian Kuhn, Olof Pock, Per Sander, Barbara Scheid, Peter Steinmetz, Benjamin St

At a depth of 3,700 meters (12,000 feet), dozens of natural chimneys stick up from the seafloor emitting hot fluid at 290 degrees Celsius (554 degrees Fahrenheit). Over thousands of years, towers of lime have piled up. This is the hydrothermal vent field of the Pescadero Basin, about 150 kilometers east of La Paz in Mexico in the Gulf of California. A marvelous place!

US researchers at the Monterey Bay Aquarium Research Institute discovered the deep-sea vent field at Pescadero Basin in 2015. A few months ago, a research team went back on board the Schmidt Ocean Institute ship Falkor to explore this special place. They mapped the seafloor, recorded high-resolution video and brought back rocks and animal samples.

Due to volcanic activity underground, hot water creeps out of the seafloor, containing chemicals such as hydrogen sulfide - a gas that smells like rotten eggs. It is extremely toxic to humans, but some bacteria can metabolize it and gain energy from it. Those bacteria thrive down here at Pescadero Basin and form these thick, fluffy looking bacterial mats.

The vents are buried in the sediment, so the hot liquid reacts with rocks before it escapes. Therefore, the liquid is clear (like you can see in this picture). At another type of vent called a 'black smoker', dark, metal-rich fluid leaves the chimneys instead. Pescadero harbors life quite different from that what was found at other vent fields explored previously.

The vents are densely covered with tubeworms (Oasisia alvinae). These sessile invertebrates live in chitin tubes just a bit wider than their body. Tubeworms like this one were discovered in the 1970s at a vent field near the Galapagos. The researchers were amazed by how many of these animals live at Pescadero. They are literally everywhere.

Oasisia tubeworms dont have a mouth or a digestive system. Instead, the animals take up hydrogen sulfide and oxygen from the water with their orange-red plumes. They feed the nutrients into a bag filled with bacteria. The bacteria then generate energy for them. It works similar to the bacteria in our guts digesting food for us.

In Pescadero Basin, researchers found species they hadnt seen anywhere else before. Like this iridescent blue scale worm, named Peinaleopolynoe orphanae. Across their back, they have thick discs that refract light - just like the wings of a butterfly. The researchers watched the creatures fighting with each other. They have big jaws which they can project during a fight.

This strange creature is called Xenoturbella profunda, but scientists often call it simply the sock worm. This turns out to be quite literal they are just a bag with a mouth underneath. Scientists saw these strange animals gliding very slowly over the seafloor. They seem to feed on clams, as researchers found clam DNA inside their bodies. How they catch and eat their prey? Nobody knows.

Some animals such as tubeworms, scale worms and Xenoturbella live directly on the hydrothermal vents. Others, though, just float by, like fish or octopuses. Or this guy here, a siphonophore. It resembles a jellyfish, but it's not one. Its more closely related to the venomous Portuguese man o' war.

Apart from animals and rocks, there is more to see in the Pescadero Basin. Underwater lakes like this one, for example. They develop when hot fluid gets trapped under rocks or within caves and cannot escape.

An underwater-robot pilot on the ship steers the remotely-operated vehicle from vent to vent. Via a tether, the robot sends back data and high-resolution video footage to the surface. The researchers can thus see in real-time whats going on down there. An awesome experience, for sure.

The underwater robot has an arm with which it can pick up rocks and animals and bring them back to the surface. But most animals lose their colors and shape pretty soon when conserved in alcohol in the researchers lab. This for a example is a sea cucumber from Pescadero Basin, beautifully colored in life not anymore.

Author: Brigitte Osterath

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Model organisms are more than just monkeys and mice - DW (English)

Richard Bransons SPAC to Merge With Gene-Testing Firm 23andMe – Barron’s

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Billionaire Richard Branson has invested in everything from commercial space travel to record labels. Now he is getting into the human genome business.

His blank-check special-purpose company, VG Acquisition Corp. (ticker: VGAC), is merging with the gene-testing company 23andMe and will list it publicly on the New York Stock Exchange under the ticker ME. Under the deal, which values the company at around $3.5 billion, existing shareholders of the gene-testing firm will own 81% of the business.

Branson and Anne Wojcicki, the CEO of 23andMe, will each invest $25 million in a $250 million private investment in public equity, or PIPE. Other investors include funds managed by Fidelity, Altimeter Capital, Casdin Capital, and Foresite Capital. It is expected to close in the second quarter.

The transaction will bring 23andMe gross proceeds of up to $759 million, according to a statement disclosing the deal. That includes the $250 million PIPE and up to $509 million in a VG Acquistion trust account.

For Branson, it is a foray into the booming health-care services industry. 23andMe sells an at-home testing kit that has become popular with consumers who want to learn about their genetic backgrounds. The information can reveal details about genetic health risks in addition to ancestry.

Test users also have the option to participate in genetic research, which 80% accept. The insights from this research can be used to develop future therapies for cancer, heart, and lung disease, among others, the company said.

We have a huge opportunity to help personalize the entire experience at scale, allowing individuals to be more proactive about their health and wellness, said Wojcicki. Through a genetics-based approach, we fundamentally believe we can transform the continuum of healthcare.

Branson said in the same statement that he was excited to see 23andMe make a positive difference to more people.

Consumer genetic testing fits into the growing segment of personalized medicine and health care. Its also an area of controversy over privacy issues.

In 2018, 23andMe joined forces with GlaxoSmithKline (GSK) in a four-year project to use the genetic data 23andMe gathers to develop new drugs.

VG Acquisition shares jumped more than 14% on Thursday, compared with a 0.9% gain in the S&P 500.

Write to Liz Moyer at Liz.Moyer@barrons.com

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Richard Bransons SPAC to Merge With Gene-Testing Firm 23andMe - Barron's

Using proteogenomics to improve the treatment of squamous cell carcinoma – Baylor College of Medicine News

Patients with head and neck squamous cell carcinoma (HNSCC), the sixth most common epithelial cancer worldwide, are treated with surgery, chemotherapy and radiotherapy. In addition, targeted agents, including an EGFR monoclonal antibody (mAb) inhibitor and two programmed cell death protein 1 (PD-1) inhibitors, have been approved by the U.S. Food and Drug Administration for HNSCC treatment, but response rates are moderate.

In this study, researchers led by Baylor College of Medicine, Johns Hopkins University and the National Cancer Institutes Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigated what new insight proteogenomic analysis might offer into understanding why certain patients respond to certain treatments while other patients do not. They propose that their findings may help better match patients to an appropriate course of treatment in the future.

The team profiled proteins, phosphosites (a site on a protein associated with phosphorylation) and signaling pathways in 108 human papillomavirus-negative HNSCC tumors in order to understand how genetic aberrations drive tumor behavior and response to therapies.

We found three subtypes of head and neck squamous cell carcinoma, and each subtype may be a good candidate for a different type of therapy EGFR inhibitors, CDK inhibitors or immunotherapy, saidDr. Bing Zhang, lead contact of the study and professor in theLester and Sue Smith Breast Centerand theDepartment of Molecular and Human Geneticsat Baylor. We also identified candidate biomarkers that could be used to match patients to effective therapies or clinical trials.

One important finding involved matching HNSCC patients to EGFR mAb inhibitors. Cetuximab, an EGFR mAb medication, was approved by the FDA in 2006 as the first targeted therapy for HNSCC, however the success rate for this treatment is low. Moreover, EGFR amplification or overexpression cannot predict response to EGFR mAbs. In this study, researchers found that EGFR ligands, instead of EGFR itself, act as the limiting factor for EGFR pathway activation. When ligand is low, the downstream pathway will not be triggered, even if EGFR protein is highly overexpressed.

We proposed that the EGFR ligand should be used as a biomarker, rather than EGFR amplification or overexpression, to help select patients for the EGFR monoclonal antibody treatment, said Zhang, a member of the Dan L Duncan Comprehensive Cancer Center, a Cancer Prevention & Research Institute of Texas (CPRIT) Scholar and aMcNair Scholarat Baylor.

Tumors with high EGFR amplification do not necessarily have high levels of EGFR ligands, which may underlie their lack of response to EGFR mAb therapy. The team confirmed this hypothesis by analyzing previously published data from patient-derived xenograft models and a clinical trial.

Additionally, tracking a key tumor suppressor known as Rb (retinoblastoma), the research team identified a striking finding that suggests that Rb phosphorylation status could potentially be a better indicator of a patients response to CDK4/6 inhibitor therapy. The study showed that the many mutations in the genes regulating CDK4/6 activity were neither necessary nor sufficient for activation of CDK4/6.

The team found that the CDK4 activity was best measured through Rb phosphorylation measurements, thus identifying a potential measure for patient selection in CDK inhibitor clinical trials.

The research team also found important insights into the effectiveness of immunotherapy. PD-1 inhibitors target the interaction between immune checkpoints PD-1 and PD-L1, but success rates of immunotherapy are low, even when PD-L1 expression is used for patient selection. The researchers examined tumors with high expression of PD-L1 and found that when a tumor overexpresses PD-L1, it also upregulates other immune checkpoints, thus allowing the tumor growth despite the use of PD-1 inhibitors.

This observation suggests that PD-1- and PD-L1-activated tumors with hot immune environments may require multiple types of immunotherapy, which target different immune checkpoint proteins, to be effective.Conversely, tumors with cold immune environments are not good targets for immunotherapy.

Immune-cold tumors are tumors that contain few if any infiltrating immune T cells. Examination of how a tumor becomes immune-cold showed that the problem stems from a flaw in its antigen presentation pathway, a first step toward triggering an immune response against tumor antigens. In immune-cold tumors multiple key gene components of the antigen presentation pathway were deleted. As a result, although tumor antigens are being expressed, the immune system is not able to recognize them on the surface of cancer cells and therefore fails to activate the bodys defense system against the tumor. These deletions have the potential to be effective targets for future therapies.

This study extends our biological understanding of HPV-negative HNSCCs and generates therapeutic hypotheses that may serve as the basis for future studies and clinical trials toward molecularly-guided precision medicine treatment of this aggressive cancer type, saidDr. Daniel W. Chan, co-corresponding author of the study, professor of pathology and oncology, and director of theCenter for Biomarker Discovery and Translationat theJohns Hopkins University School of Medicine.

Find all the details of this study and a full list of contributing authors in the journalCancer Cell.

This work was supported by grants U24 CA210954, U24 CA210985, U24 CA210972, U24 CA210979, U24 CA210986, U24 CA214125, U24 CA210967, and U24 CA210993 from the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC), by a Cancer Prevention Institute of Texas (CPRIT) award RR160027, by grant T32 CA203690 from the Translational Breast Cancer Research Training Program, and by funding from the McNair Medical Institute at the Robert and Janice McNair Foundation.

By Molly Chiu

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Using proteogenomics to improve the treatment of squamous cell carcinoma - Baylor College of Medicine News