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Category Archives: Human Genetics

Forget me not – Triad City Beat

Posted: August 25, 2017 at 3:41 am

The community room looks like the interior of any well-appointed modern house from Starmount to Summerfield, with ocean-blue walls, mahogany-style tables matched with high-backed chairs, a sleek metallic refrigerator and comfortable couches.

Theres one key difference: The dining room, kitchen, living area and bathroom are collapsed into one large room with no dividers. Located on the third floor of a repurposed textile building across the street from Revolution Mill, the community room at the Center for Outreach in Alzheimers, Age and Community Health, or COAACH, functions as a classroom for families learning how to take care of a loved one developing Alzheimers disease or dementia.

The team wanted it to look like a home, said Donna Bradby, a publicist at NC A&T University, so you could cook a healthy meal, sit your loved one down at the table and then do things like transferring them to the bathroom and helping them brush their teeth.

Bradby gestured toward the full-length mirror at the end of the room.

My aunt, Annie Ruth Ingram, had Alzheimers, Bradby said. We stood in front of that mirror. She said, Who is that lady? I said, Oh, Aunt Annie Ruth. Thats you!

Annie Ruths husband, Charlie, passed away before she did, and its not uncommon for spouses to precede loved ones with Alzheimers in death. Caring for someone suffering from the disease, which progressively robs people of memory, cognition, muscle movement and personality, can take a heavy toll. Caregivers experience high levels of stress and cope with depression, often neglecting their own health and missing doctors appointments.

Those who take care of people with Alzheimers and other forms of dementia are twice as likely to report substantial emotional, financial and physical difficulties as other caregivers, according to the Alzheimers Association. Two thirds are women, and 34 percent are age 65 or older. A quarter of caregivers are considered a sandwich generation, meaning that theyre also taking care of a child under the age of 18.

Research has shown that Alzheimers is twice as likely to affect African Americans (and 1.5 times more likely to affect Hispanics) than non-Hispanic whites, but until about 10 years ago there was little research into why the disease strikes African Americans with such ferocity.

The answer is gradually coming into focus, thanks in part to the research of Dr. Goldie Byrd, the founding director of COAACH, which opened in 2014. A recent article by journalist and novelist Marita Golden in the Washington Post described the Greensboro center as a kind of ground zero for innovative, cross-disciplinary and community-based responses to the disease.

A complex interplay of environmental and genetic factors accounts for why Alzheimers inflicts a disparate toll on African Americans. An understanding of the interplay can help people make lifestyle choices that reduce the risk of the diseases onset, and researchers hope that understanding genetic factors will lead to the development of drugs to treat it. Alzheimers medications currently only address symptoms, without preventing, curing or slowing the disease.

On the environmental side of the equation, a series of studies presented at the 2017 Alzheimers Association International Conference in London in July added to a growing body of evidence that racial inequities increase the risk of Alzheimers and other dementias. Researchers at the University of Wisconsin found that African Americans were 60 percent more likely than whites to experience a stressful life event such as losing a job, the death of a child, combat, or growing up with a parent who abused drugs, which correlated with deterioration in cognition later in life. Other studies presented at the conference found that people born in states with high infant mortality rates a proxy for harsh early-life conditions and neighborhoods disadvantaged by poverty, poor housing and limited educational and employment opportunities were more likely to experience poorer cognitive function and dementia late in life.

Despite the diseases disparate impact, the science of how Alzheimers affects African Americans was woefully behind as recently as 15 years ago. Byrd joined the faculty at NC A&T as chair of the biology department in 2003, and that year she completed a sabbatical at the Duke Center for Human Genetics, where she helped initiate a study on Alzheimers. At the time, the university had 7,000 blood samples, but less than 50 were drawn from African-American volunteers.

We wanted to increase our knowledge about Alzheimers, particularly underrepresented groups like African Americans and Hispanics, Byrd said. These groups had a disproportionate burden, but there was so little in the literature about Alzheimers in these groups, particularly Alzheimers relationship to genetics.

As Byrd continued her research at her new post at A&T, the first challenge was to figure out how to overcome reluctance among African Americans to participating in studies.

We began by going into the community and asking different stakeholders lay people, the faith-based communities; we went to health fairs and barbershops and we asked people if they would participate in a study, Byrd recalled. What would the barriers be? What would the motivations be?

Distrust among African Americans due to the legacy of atrocities like the Tuskegee experiment a project launched by the US Public Health Service in 1932 in which researchers studied black men with syphilis without their informed consent and without treating them for the disease was an obvious hurdle. And while there are continuing reasons for African Americans and other underrepresented groups to distrust the medical establishment, Byrd emphasized that ethical research coupled with culturally calibrated outreach can overcome barriers.

People struggle with lack of access and the indifference when theyre treated even in 2017, Byrd said. They notice when they go to the doctor and they dont see people who look like them in 2017. There are recent studies that show that people of color dont get the same level of care.

African Americans will participate in studies, she added. Stereotypically, people think African Americans wont participate because of these atrocities. There are very good reasons for there to be hesitation and concern. We have to take the time to communicate with them to make sure they feel comfortable. We cant assume people who are mistreated are going to be at the front of the line unless we as researchers assure them that theyre safe, that were going to handle them and their specimens in an honest and respectful way, and we reassure them they can stop at any time.

The family-support component that became a core pillar of the COAACH center emerged as natural extension of Dr. Byrds understanding that she needed to design a study that would earn the trust of African-American volunteers.

The person I was working with we agreed we would create an environment that specifically targeted African Americans and engaged them directly in what the study was, that would create learning opportunities for this community, that would keep them engaged and keep them in the loop around whats happening with the research, Byrd said.

Although COAACH opened in response to a need to engage African Americans in Alzheimers research, Byrd and other staff members emphasize that the programs at the center are open to people of all races.

We created our COAACH center to assure not only African Americans but people of all races that we were there, and we werent going to get them into the study and leave, Byrd said. If people needed information about diabetes, which is linked to Alzheimers, they could call. If a church was having a health fair, they could call. We created a support group that people can attend; they dont have to be African American. They can attend Lunch & Learn.

Through Dr. Byrds efforts, the bank of data on African Americans with Alzheimers has dramatically expanded. As part of the Alzheimers Disease Genetics Consortium, which includes several other institutions, Byrd was part of a study that dramatically expanded the number of DNA specimens under review. In 2013, the consortium discovered that a variation in the ABCA7 gene that had previously been linked to Alzheimers was found to have a stronger link in African Americans than non-Hispanic whites.

Finding a gene link like ABCA7 gives researchers clues about what causes Alzheimers because variants might cause it to dysfunction and affect different populations in different ways.

In the hope of learning more about how genetics factors into the disease, COAACH is recruiting families with more than one member who has Alzheimers for an ongoing study. The center has collected samples from people in North Carolina, along with Virginia and New York.

There may be other genes like ABCA7 that are associated with the disease, Byrd said. There may be [treatments] that are specific to one population and not to another. Thats important because if we only did research in one population everything ends up being generalized. Our hope is there will be therapies and interventions that are specific to populations and not generalized. The advantage of doing studies is that well be much more inclusive and everyone will benefit.

There are many studies and clinical trials going on right now, she continued. We dont have any cure right now. We dont have anything to slow the disease. There are drugs that can assist with the symptoms. We are very hopeful that the pharmaceutical companies working with research institutions will come up a drug that can halt or slow the disease.

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Forget me not – Triad City Beat

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Using Genetics to Uncover Human History – JD Supra (press release)

Posted: August 22, 2017 at 11:32 pm

Human history is often something modern man only sees as through a glass, darkly. This is particularly the case when that history did not occur in the Mediterranean, the Nile Valley, India, or China, or when there is no written record on which scholars can rely. Exacerbating the disrupting effects of time on history can be when that history occurs in a region where extensive migration has disrupted whatever temporarily stable civilization happened to have taken root at that place at any particular time.

But humans leave traces of themselves in their history and a variety of such traces have been the source of reconstructions outside conventional sources. Luigi Cavalli-Sforza began the study of human population genetics as a way to understand this history in 1971 in The Genetics of Human Populations, and later extended these studies to include language and how it influences gene flow between human populations. More recent efforts to use genetics to reconstruct history include Deep Ancestry: The Landmark DNA Quest to Decipher Our Distant Past by Spencer Wells (National Geographic: 2006), and The Seven Daughters of Eve: The Science that Reveals our Genetic Ancestry by Brian Sykes (Carrol & Graf: 2002). And even more recently, genetic studies have illuminated the “fine structure” of human populations in England (see “Fine-structure Genetic Mapping of Human Population in Britain”).

Two recent reports illustrate how genetics can inform history: the first, in the American Journal of Human Genetics entitled “Continuity and Admixture in the Last Five Millennia of Levantine History from Ancient Canaanite and Present-Day Lebanese Genome Sequences”; and a second in the Proceedings of the National Academy of Sciences USA, entitled “Genomic landscape of human diversity across Madagascar.” In the first study, authors* from The Wellcome Trust Sanger Institute, University of Cambridge, University of Zurich, University of Otago, Bournemouth University, Lebanese American University, and Harvard University found evidence of genetic admixture over 5,000 years of a Canaanite population that has persisted in Lebanese populations into the modern era. This population is interesting for historians in view of the central location of the ancestral home of the Canaanites, the Levant, in the Fertile Crescent that ran from Egypt through Mesopotamia. The Canaanites also inhabited the Levant during the Bronze Age and provide a critical link between the Neolithic transition from hunter gatherer societies to agriculture. This group (known to the ancient Greeks as the Phoenicians) is also a link to the great early societies recognized through their historical writings and civilizations (including the Egyptians, Assyrians, Babylonians, Persians, Greeks, and Romans); if the Canaanites had any such texts or other writings they have not survived. In addition, the type of genetic analyses that have been done for European populations has not been done for descendants of inhabitants of the Levant from this historical period. This paper uses genetic comparisons between 99 modern day residents of Lebanon (specifically, from Sidon and the Lebanese interior) and ancient DNA (aDNA) from ~3,700 year old genomes from petrous bone of individuals interred in gravesites in Sidon. For aDNA, these analyses yielded 0.4-2.3-fold genomic DNA coverage and 53-264-fold mitochondrial DNA coverage, and also compared Y chromosome sequences with present-day Lebanese, two Canaanite males and samples from the 1000 Genomes Project. Over one million single nucleotide polymorphisms (SNPs) were used for comparison.

These results indicated that the Canaanite ancestry was an admixture of local Neolithic populations and migrants from Chalcolithic (Copper Age) Iran. The authors estimate from these linkage disequilibrium studies that this admixture occurred between 6,600 and 3,550 years ago, a date that is consistent with recorded mass migrations in the region during that time. Perhaps surprisingly, their results also show that the majority of the present-day Lebanese population has inherited most of their genomic DNA from these Canaanite ancestors. These researchers also found traces of Eurasian ancestry consistent with conquests by outside populations during the period from 3,750-2,170 years ago, as well as the expansion of Phoenician maritime trade network that extended during historical time to the Iberian Peninsula.

The second paper arose from genetic studies of an Asian/African admixture population on Mozambique. This group** from the University of Toulouse, INSERM, the University of Bordeaux, University of Indonesia, the Max Plank Institute for Evolutionary Anthropology, Institut genomique, Centre Nacional de Genotypage, University of Melbourne, and the Universite de la Rochelle, showed geographic stratification between ancestral African (mostly Bantu) and Asian (Austronesean) ancestors. Cultural, historical, linguistic, ethnographic, archeological, and genetic studies supports the conclusion that Madagascar residents have traits from both populations but the effects of settlement history are termed “contentious” by these authors. Various competing putative “founder” populations (including Arabic, Indian, Papuan, and/or Jewish populations as well as first settlers found only in legend, under names like “Vazimba,” “Kimosy,” and “Gola”) have been posited as initial settlers. These researchers report an attempt to illuminate the ancestry of the Malagasy by a study of human genetics.

These results showed common Bantu and Austronesian descent for the population with what the authors termed “limited” paternal contributions from Europe and Middle Eastern populations. The admixture of African and Austronesian populations occurred “recently” (i.e., over the past millennium) but was gender-biased and heterogeneous, which reflected for these researchers independent colonization by the two groups. The results also indicated that detectable genetic structure can be imposed on human populations over a relatively brief time (~ a few centuries).

Using a “grid-based approach” the researchers performed a high-resolution genetic diversity study that included maternal and paternal lineages as well as genome-wide data from 257 villages and over 2,700 Malagasy individuals. Maternal inheritance patterns were interrogated using mitochondrial DNA and patterns of paternity assayed using Y chromosomal sequences. Non-gender specific relationships were assessed through 2.5 million SNPs. Mitochondrial DNA analyses showed maternal inheritance from either African or East Asian origins (with one unique Madagascar variant termed M23) in roughly equal amounts, with no evidence of maternal gene flow from Europe or the Middle East. The M23 variant shows evidence of recent (within 900-1500 years) origin. Y chromosomal sequences, in contrast are much more prevalent from African origins (70.7% Africa:20.7% East Asia); the authors hypothesize that the remainder may reflect Muslim influences, with evidence of but little European ancestry.

Admixture assessments support Southeast Asian (Indonesian) and East African source populations for the Malagasy admixture. These results provide the frequency of the African component to be ~59%, the Asian component frequency to be ~37%, and the Western European component to have a frequency of about 4% (albeit with considerable variation, e.g., African ancestry can range from ~26% to almost 93%). Similar results were obtained when the frequency of chromosomal fragments shared with other populations were compared to the Malagasy population (finding the closest link to Asian populations from south Borneo, and excluding Indian, Somali, and Ethiopian populations, although the analysis was sensitive in one individual to detect French Basque ancestry). The split with ancestral Asian populations either occurred ~2,500 years ago or by slower divergence between ~2,000-3,000 years ago, while divergence with Bantu populations occurred more recently (~1,500 years ago).

There were also significant differences in geographic distribution between descendants of these ancestral populations. Maternal African lineages were found predominantly in north Madagascar, with material Asian lineages found in central and southern Madagascar (from mtDNA analyses). Paternal lineages were generally much lower overall for Asian descendants (~30% in central Madagascar) based on Y chromosome analyses. Genome-wide analyses showed “highlanders” had predominantly Asian ancestry (~65%) while coastal inhabitants had predominantly (~65%) African ancestry; these results depended greatly on the method of performing the analyses which affected the granularity of the geographic correlates. Finally, assessing admixture patterns indicated that the genetic results are consistent with single intermixing event (500-900 years ago) for all but one geographic area, which may have seen a first event 28 generations ago and a second one only 4 generations ago. These researchers also found evidence of at least one population bottleneck, where the number of individuals dropped to a few hundred people about 1,000-800 years ago.

These results are represented pictorially in the paper:

In view of the current political climate, the eloquent opening of the paper deserves attention:

Ancient long-distance voyaging between continents stimulates the imagination, raises questions about the circumstances surrounding such voyages, and reminds us that globalization is not a recent phenomenon. Moreover, populations which thereby come into contact can exchange genes, goods, ideas and technologies.

* Marc Haber, Claude Doumet-Serhal, Christiana Scheib, Yali Xue, Petr Danecek, Massimo Mezzavilla, Sonia Youhanna, Rui Martiniano, Javier Prado-Martinez, Micha Szpak, Elizabeth Matisoo-Smith, Holger Schutkowski, Richard Mikulski, Pierre Zalloua, Toomas Kivisild, Chris Tyler-Smith

** Denis Pierrona, Margit Heiskea, Harilanto Razafindrazakaa, Ignace Rakotob, Nelly Rabetokotanyb, Bodo Ravololomangab, Lucien M.-A. Rakotozafyb, Mireille Mialy Rakotomalalab, Michel Razafiarivonyb, Bako Rasoarifetrab, Miakabola Andriamampianina Raharijesyb, Lolona Razafindralambob, Ramilisoninab, Fulgence Fanonyb, Sendra Lejamblec, Olivier Thomasc, Ahmed Mohamed Abdallahc, Christophe Rocherc,, Amal Arachichec, Laure Tonasoa, Veronica Pereda-lotha, Stphanie Schiavinatoa, Nicolas Brucatoa, Francois-Xavier Ricauta, Pradiptajati Kusumaa,d,e, Herawati Sudoyod,e, Shengyu Nif, Anne Bolandg, Jean-Francois Deleuzeg, Philippe Beaujardh, Philippe Grangei, Sander Adelaarj, Mark Stonekingf, Jean-Aim Rakotoarisoab, Chantal Radimilahy, and Thierry Letelliera

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Using Genetics to Uncover Human History – JD Supra (press release)

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Gene editing used to repair diseased genes in embryos – NHS Choices

Posted: at 11:32 pm

Deadly gene mutations removed from human embryos in landmark study, reports The Guardian. Researchers have used a gene-editing technique to repair faults in DNA that can cause an often-fatal heart condition called hypertrophic cardiomyopathy.

This inherited heart condition is caused by a genetic change (mutation) in one or more genes. Babies born with hypertrophic cardiomyopathy have diseased and stiff heart muscles, which can lead to sudden unexpected death in childhood and in young athletes.

In this latest study researchers used a technique called CRISPR-cas9 to target and then remove faulty genes. CRISPR-cas9 acts like a pair of molecular scissors, allowing scientists to cut out certain sections of DNA. The technique has attracted a great deal of excitement in the scientific community since it was released in 2014. But as yet, there have been no practical applications for human health.

The research is at an early stage and cannot legally be used as treatment to help families affected by hypertrophic cardiomyopathy. And none of the modified embryos were implanted in the womb.

While the technique showed a high degree of accuracy, its unclear whether it is safe enough to be developed as a treatment. The sperm used in the study came from just one man with faulty genes, so the study needs to be repeated using cells from other people, to be sure that the findings can be replicated.

Scientists say it is now important for society to start a discussion about the ethical and legal implications of the technology. It is currently against the law to implant genetically altered human embryos to create a pregnancy, although such embryos can be developed for research.

The study was carried out by researchers from Oregon Health and Science University and the Salk Institute for Biological Studies in the US, the Institute for Basic Science and Seoul University in Korea, and BGI-Shenzen and BGI-Quingdao in China. It was funded by Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation and the Leona M. and HarryB. Helmsley Charitable Trust and the Shenzhen Municipal Government of China. The study was published in the peer-reviewed journal Nature.

The Guardian carried a clear and accurate report of the study. While their reports were mostly accurate, ITV News, Sky News and The Independent over-stated the current stage of research, with Sky News and ITV News saying it could eradicate thousands of inherited conditions and the Independent claiming it opens the possibility for inherited diseases to be wiped out entirely. While this may be possible, we dont know whether other inherited diseases might be as easily targeted as this gene mutation.

Finally, the Daily Mail rolls out the arguably tired clich of the technique leading to designer babies, which seems irrelevant at this point. The CRISPR-cas9 technique is only in its infancy and (ethics aside) its simply not possible to use genetic editing to select desirable characteristics – most of which are not the result of one single, identifiable gene. No reputable scientist would attempt such a procedure.

This was a series of experiments carried out in laboratories, to test the effects of the CRISPR-Cas9 technique on human cells and embryos. This type of scientific research helps us understand more about genes and how they can be changed by technology. It doesnt tell us what the effects would be if this was used as a treatment.

Researchers carried out a series of experiments on human cells, using the CRISPR-cas9 technique first on modified skin cells, then on very early embryos, and then on eggs at the point of fertilisation by sperm. They used genetic sequencing and analysis to assess the effects of these different experiments on cells and how they developed, up to five days. They looked specifically to see what proportion of cells carrying faulty mutations could be repaired, whether the process caused other unwanted mutations, and whether the process repaired all cells in an embryo, or just some of them.

They used skin cells (which were modified into stem cells) and sperm from one man, who carried the MYBPC3 mutation in his genome, and donor eggs from women without the genetic mutation. This is the mutation known to cause hypertrophic cardiomyopathy.

Normally in such cases, roughly half the embryos would have the mutation and half would not, as theres a 50-50 chance of the embryo inheriting the male or female version of the gene.

The CRISPR-cas9 technique can be used to select and delete specific genes from a strand of DNA. When this happens, usually the cut ends of the strand join together, but this causes problems so cant be used in the treatment of humans. The scientists created a genetic template of the healthy version of the gene, which they introduced at the same time as using CRISPR-cas9 to cut the mutated gene. They hoped the DNA would repair itself with a healthy version of the gene.

One important problem with changing genetic material is the development of mosaic embryos, where some of the cells have corrected genetic material and others have the original faulty gene. If that happened, doctors would not be able to tell whether or not an embryo was healthy.

The scientists needed to test all the cells in the embryos produced in the experiment, to see whether all cells had the corrected gene or whether the technique had resulted in a mixture. They also did whole genome sequencing on some embryos, to test for unrelated genetic changes that might have been introduced accidentally during the process.

All embryos in the study were destroyed, in line with legislation about genetic research on embryos.

Researchers found that the technique worked on some of the stem cells and embryos, but worked best when used at the point of fertilisation of the egg. There were important differences between the way the repair worked on the stem cells and the egg.

Only 28% of the stem cells were affected by the CRISPR-cas9 technique. Of these, most repaired themselves by joining the ends together, and only 41% were repaired by using a corrected version of the gene.

67% of the embryos exposed to CRISPR-cas9 had only the correct version of the gene higher than the 50% that would have been expected had the technique not been used. 33% of embryos had the mutated version of the gene, either in some or all their cells.

Importantly, the embryos didnt seem to use the template injected into the zygote to carry out the repair, in the way the stem cells did. They used the female version of the healthy gene to carry out the repair, instead.

Of the embryos created using CRISPR-cas9 at the point of fertilisation, 72% had the correct version of the gene in all their cells, and 28% had the mutated version of the gene in all their cells. No embryos were mosaic a mixture of cells with different genomes.

The researchers found no evidence of mutations induced by the technique, when they examined the cells using a variety of techniques. However, they did find some evidence of gene deletions caused by DNA strands splicing (joining) themselves together without repairing the faulty gene.

The researchers say they have demonstrated how human embryos employ a different DNA damage repair system to adult stem cells, which can be used to repair breaks in DNA made using the CRISPR-cas9 gene-editing technique.

They say that targeted gene correction could potentially rescue a substantial portion of mutant human embryos, and increase the numbers available for transfer for couples using pre-implantation diagnosis during IVF treatment.

However, they caution that despite remarkable targeting efficiency, CRISPR-cas9-treated embryos would not currently be suitable for transfer. Genome editing approaches must be further optimised before clinical application can be considered, they say.

Currently, genetically-inherited conditions like hypertrophic cardiomyopathy cannot be cured, only managed to reduce the risk of sudden cardiac death. For couples where one partner carries the mutated gene, the only option to avoid passing it on to their children is pre-implantation genetic diagnosis. This involves using IVF to create embryos, then testing a cell of the embryo to see whether it carries the healthy or mutated version of the gene. Embryos with healthy versions of the gene are then selected for implantation in the womb.

Problems arise if too few or none of the embryos have the correct version of the gene. The researchers suggest their technique could be used to increase the numbers of suitable embryos. However, the research is still at an early stage and has not yet been shown to be safe or effective enough to be considered as a treatment.

The other major factor is ethics and the law. Some people worry that gene editing could lead to designer babies, where couples use the tool to select attributes like hair colour, or even intelligence. At present, gene editing could not do this. Most of our characteristics, especially something as complex as intelligence, are not the result of one single, identifiable gene, so could not be selected in this way. And its likely that, even if gene editing treatments became legally available, they would be restricted to medical conditions.

Designer babies aside, society needs to consider what is acceptable in terms of editing human genetic material in embryos. Some people think that this type of technique is “playing God” or is ethically unacceptable because it involves discarding embryos that carry faulty genes. Others think that its rational to use the scientific techniques we have developed to eliminate causes of suffering, such as inherited diseases.

This research shows that the questions of how we want to legislate for this type of technique are becoming pressing. While the technology is not there yet, it is advancing fast. This research shows just how close we are getting to making genetic editing of human embryos a reality.

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Gene editing used to repair diseased genes in embryos – NHS Choices

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How Jewish activism has wiped out Tay-Sachs – The Times of Israel

Posted: at 11:32 pm

JTA Parents of children born with Tay-Sachs disease talk about three deaths.

There is the moment when parents first learn that their child has been diagnosed with the fatal disease. Then there is the moment when the childs condition has deteriorated so badly blind, paralyzed, non-responsive that he or she has to be hospitalized. Then theres the moment, usually by age 5, when the child finally dies.

There used to be an entire hospital unit 16 or 17 beds at Kingsbook Jewish Medical Center in Brooklyn devoted to taking care of these children. It was often full, with a waiting list that admitted new patients only when someone elses child had died.

But by the late 1990s that unit was totally empty, and it eventually shut down. Its closure was a visible symbol of one of the most dramatic Jewish success stories of the past 50 years: the near-eradication of a deadly genetic disease.

Since the 70s, the incidence of Tay-Sachs has fallen by more than 90 percent among Jews, thanks to a combination of scientific advances and volunteer community activism that brought screening for the disease into synagogues, Jewish community centers and, eventually, routine medical care.

Until 1969, when doctors discovered the enzyme that made testing possible to determine whether parents were carriers of Tay-Sachs, 50 to 60 affected Jewish children were born each year in the United States and Canada. After mass screenings began in 1971, the numbers declined to two to five Jewish births a year, said Karen Zeiger, whose first child died of Tay-Sachs.

In the days before Facebook or email, activists and organizers spread the word about mass Tay-Sachs screenings through newspaper and magazine articles, posters at synagogues, and items in Jewish organizational newsletters. (Courtesy of National Tay-Sachs and Allied Diseases Association/via JTA)

It had decreased significantly, said Zeiger, who until her retirement in 2000 was the State of Californias Tay-Sachs prevention coordinator. Between 1976 and 1989, there wasnt a single Jewish Tay-Sachs birth in the entire state, she said.

The first mass screening was held on a rainy Sunday afternoon in May 1971 at Congregation Beth El in Bethesda, Maryland. The site was chosen in part for its proximity to Johns Hopkins University in Baltimore. One of the two doctors who discovered the missing hexosaminidase A enzyme, John OBrien, was visiting a lab there, and another Johns Hopkins doctor, Michael Kaback, had recently treated two Jewish couples with Tay-Sachs children, including Zeigers. Zeigers husband, Bob, was also a doctor at Johns Hopkins.

The screenings used blood tests to check for the missing enzyme that identified a parent as a Tay-Sachs carrier.

With the help of 40 trained lay volunteers and 15 physicians, more than 1,500 people volunteered for testing and were processed through the system in about 5 hours, Dr. Kaback later recalled in an article in the journal Genetics in Medicine. For me, it was like having written a symphony and hearing it for the first time and it went beautifully, without glitches.

A machine to process the tests cost $15,000. We had bazaars, cake sales, sold stockings, and thats how we raised money for the machine, Zeiger said.

Before screening, couples in which both parents were Tay-Sachs carriers almost always stopped having children after they had one child with Tay-Sachs, for fear of having another, Ruth Schwartz Cowan wrote it in her book Heredity and Hope: The Case for Genetic Screening.

But with screening, Tay-Sachs could be detected before birth, and carrier couples felt encouraged to have children, she wrote.

People named their kids after him

Dr. Kabacks work helped enable thousands of parents who were Tay-Sachs carriers to have other, healthy children.

What he did for Tay-Sachs and how he helped so many families was amazing, Zeiger said. People named their kids after him.

The screenings were transformative, and the campaign to get Jews tested for Tay-Sachs took off. This was before the advent of Facebook or email, so activists and organizers spread the word about screenings through newspaper and magazine articles, posters at synagogues, and items in Jewish organizational newsletters. Volunteers and medical professionals spoke on college campuses and sent promotional prescription pads to rabbis, obstetricians, and gynecologists. Doctors and activists enlisted rabbis and community leaders to encourage couples to be tested before getting married.

Another early mass screening event was held at a school in Waltham, Massachusetts, guided by Edwin Kolodny, a professor at New York University medical school. The first mass screening in the Philadelphia area was on November 12, 1972, at the Germantown Jewish Center, and drew 800 people, according to a Yale senior thesis by David Gerber, Genetics for the Community: The Organized Response To Tay-Sachs Disease, 1955-1995.

Nearly half a century later, the Tay-Sachs screening effort remains a model for mobilizing a community against genetic disease. Parent activists, scientists and doctors are trying to emulate that model with other diseases and other populations.

You cant be complacent, because now there are 200 diseases you can test for

You cant be complacent, because now there are 200 diseases you can test for, said Kevin Romer, president of the Matthew Forbes Romer Foundation and a past president of the National Tay-Sachs and Allied Diseases Association. The foundation is named for Romers son Matthew, who died of Tay-Sachs in 1996.

Romer and others involved with this issue stress the importance of screening interfaith couples, too. Non-Jews may also benefit from pre-conception screening for Tay-Sachs and other diseases. Some research indicates, for example, that Louisiana Cajuns, French Canadians and individuals with Irish lineage may also have an elevated incidence of Tay-Sachs.

Heredity and Hope: The Case for Genetic Screening, by Ruth Schwartz Cowan. (Courtesy)

Scientific progress means that Jews can now be screened for over 200 diseases with an at-home, mail-in test offered by JScreen. The four-year-old nonprofit affiliated with Emory Universitys Department of Human Genetics has screened thousands of people, and the subsidized fee for the test about $150 includes genetic counseling.

While some genetic tests are standard doctors office procedure for pregnant women or couples trying to get pregnant with a doctors help, JScreen aims for pre-conception screening. The test includes diseases common in those with Ashkenazi, Sephardi, and Mizrahi backgrounds as well as general population diseases, making it relevant for Jewish couples and interfaith couples.

Carrier screening gives people an opportunity to plan ahead for the health of their future families. We are taking lessons learned from earlier screening initiatives and bringing the benefits of screening to a new generation, said Karen Arnovitz Grinzaid, executive director of JScreen. It was a path pioneered by the Tay-Sachs screening that began in 1971.

In Cowans book, she mentions a chart prepared by Dr. Kaback reporting on 30 years of screening: 1.3 million people screened, 48,000 carriers detected, 1,350 carrier couples detected, 3,146 pregnancies monitored.

Kaback and his colleagues could well have stopped there, she wrote. But they did not. There is one more figure, the one that matters most and that goes the furthest in explaining why Ashkenazi Jews accept carrier screening after monitoring with pre-natal diagnosis, 2,466 unaffected offspring were born to parents who were both Tay-Sachs carriers.

This article was sponsored by and produced in partnership with JScreen, whose goal of making genetic screening as simple, accessible, and affordable as possible has helped couples across the country have healthy babies. To access testing 24/7, request a kit at JScreen.org or gift a JScreen test as a wedding present. This article was produced by JTAs native content team.

Widespread testing is credited with helping reduce the incidence of Tay-Sachs among Jews by more than 90 percent since screenings began in the early 1970s. (Courtesy of National Tay-Sachs and Allied Diseases Association/via JTA)

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Bacteria May Rig Their DNA to Speed Up Evolution – WIRED

Posted: August 20, 2017 at 5:50 pm

In 1944, a Columbia University doctoral student in genetics named Evelyn Witkin made a fortuitous mistake. During her first experiment in a laboratory at Cold Spring Harbor, in New York, she accidentally irradiated millions of E. coli with a lethal dose of ultraviolet light. When she returned the following day to check on the samples, they were all deadexcept for one, in which four bacterial cells had survived and continued to grow. Somehow, those cells were resistant to UV radiation. To Witkin, it seemed like a remarkably lucky coincidence that any cells in the culture had emerged with precisely the mutation they needed to surviveso much so that she questioned whether it was a coincidence at all.

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

For the next two decades, Witkin sought to understand how and why these mutants had emerged. Her research led her to what is now known as the SOS response, a DNA repair mechanism that bacteria employ when their genomes are damaged, during which dozens of genes become active and the rate of mutation goes up. Those extra mutations are more often detrimental than beneficial, but they enable adaptations, such as the development of resistance to UV or antibiotics.

The question that has tormented some evolutionary biologists ever since is whether nature favored this arrangement. Is the upsurge in mutations merely a secondary consequence of a repair process inherently prone to error? Or, as some researchers claim, is the increase in the mutation rate itself an evolved adaptation, one that helps bacteria evolve advantageous traits more quickly in stressful environments?

The scientific challenge has not just been to demonstrate convincingly that harsh environments cause nonrandom mutations. It has also been to find a plausible mechanism consistent with the rest of molecular biology that could make lucky mutations more likely. Waves of studies in bacteria and more complex organisms have sought those answers for decades.

The latest and perhaps best answerfor explaining some kinds of mutations, anywayhas emerged from studies of yeast, as reported in June in PLOS Biology . A team led by Jonathan Houseley, a specialist in molecular biology and genetics at the Babraham Institute in Cambridge, proposed a mechanism that drives more mutation specifically in regions of the yeast genome where it could be most adaptive.

Its a totally new way that the environment can have an impact on the genome to allow adaptation in response to need. It is one of the most directed processes weve seen yet, said Philip Hastings, professor of molecular and human genetics at Baylor College of Medicine, who was not involved in the Houseley groups experiments. Other scientists contacted for this story also praised the work, though most cautioned that much about the controversial idea was still speculative and needed more support.

Rather than asking very broad questions like are mutations always random? I wanted to take a more mechanistic approach, Houseley said. He and his colleagues directed their attention to a specific kind of mutation called copy number variation. DNA often contains multiple copies of extended sequences of base pairs or even whole genes. The exact number can vary among individuals because, when cells are duplicating their DNA before cell division, certain mistakes can insert or delete copies of gene sequences. In humans, for instance, 5 to 10 percent of the genome shows copy number variation from person to personand some of these variations have been linked to cancer, diabetes, autism and a host of genetic disorders. Houseley suspected that in at least some cases, this variation in the number of gene copies might be a response to stresses or hazards in the environment.

Jonathan Houseley leads a team that studies genome change at the Babraham Institute in Cambridge. Based on their studies of yeast, they recently proposed a mechanism that would increase the odds for adaptive mutations in genes that are actively responding to environmental challenges.

Jon Houseley/QUANTA MAGAZINE

In 2015, Houseley and his colleagues described a mechanism by which yeast cells seemed to be driving extra copy number variation in genes associated with ribosomes, the parts of a cell that synthesize proteins. However, they did not prove that this increase was a purposefully adaptive response to a change or constraint in the cellular environment. Nevertheless, to them it seemed that the yeast was making more copies of the ribosomal genes when nutrients were abundant and the demand for making protein might be higher.

Houseley therefore decided to test whether similar mechanisms might act on genes more directly activated by hazardous changes in the environment. In their 2017 paper, he and his team focused on CUP1 , a gene that helps yeast resist the toxic effects of environmental copper. They found that when yeast was exposed to copper, the variation in the number of copies of CUP1 in the cells increased. On average, most cells had fewer copies of the gene, but the yeast cells that gained more copiesabout 10 percent of the total population became more resistant to copper and flourished. The small number of cells that did the right thing, Houseley said, were at such an advantage that they were able to outcompete everything else.

But that change did not in itself mean much: If the environmental copper was causing mutations, then the change in CUP1 copy number variation might have been no more than a meaningless consequence of the higher mutation rate. To rule out that possibility, the researchers cleverly re-engineered the CUP1 gene so that it would respond to a harmless, nonmutagenic sugar, galactose, instead of copper. When these altered yeast cells were exposed to galactose, the variation in their number of copies of the gene changed, too.

The cells seemed to be directing greater variation to the exact place in their genome where it would be useful. After more work, the researchers identified elements of the biological mechanism behind this phenomenon. It was already known that when cells replicate their DNA, the replication mechanism sometimes stalls. Usually the mechanism can restart and pick up where it left off. When it cant, the cell can go back to the beginning of the replication process, but in doing so, it sometimes accidentally deletes a gene sequence or makes extra copies of it. That is what causes normal copy number variation. But Houseley and his team made the case that a combination of factors makes these copying errors especially likely to hit genes that are actively responding to environmental stresses, which means that they are more likely to show copy number variation.

The key point is that these effects center on genes responding to the environment, and that they could give natural selection extra opportunities to fine-tune which levels of gene expression might be optimal against certain challenges. The results seem to present experimental evidence that a challenging environment could galvanize cells into controlling those genetic changes that would best improve their fitness. They may also seem reminiscent of the outmoded, pre-Darwinian ideas of the French naturalist Jean-Baptiste Lamarck, who believed that organisms evolved by passing their environmentally acquired characteristics along to their offspring. Houseley maintains, however, that this similarity is only superficial.

What we have defined is a mechanism that has arisen entirely through Darwinian selection of random mutations to give a process that stimulates nonrandom mutations at useful sites, Houseley said. It is not Lamarckian adaptation. It just achieves some of the same ends without the problems involved with Lamarckian adaptation.

Ever since 1943, when the microbiologist Salvador Luria and the biophysicist Max Delbrck showed with Nobel prize-winning experiments that mutations in E. coli occur randomly, observations like the bacterial SOS response have made some biologists wonder whether there might be important loopholes to that rule. For example, in a controversial paper published in Nature in 1988, John Cairns of Harvard and his team found that when they placed bacteria that could not digest the milk sugar lactose in an environment where that sugar was the sole food source, the cells soon evolved the ability to convert the lactose into energy. Cairns argued that this result showed that cells had mechanisms to make certain mutations preferentially when they would be beneficial.

Budding yeast (S. cerevisiae) grow as colonies on this agar plate. If certain recent research is correct, a mechanism that helps to repair DNA damage in these cells may also promote more adaptive mutations, which could help the cells to evolve more quickly under harsh circumstances.

Jon Houseley/QUANTA MAGAZINE

Experimental support for that specific idea eventually proved lacking, but some biologists were inspired to become proponents of a broader theory that has come to be known as adaptive mutation. They believe that even if cells cant direct the precise mutation needed in a certain environment, they can adapt by elevating their mutation rate to promote genetic change.

The work of the Houseley team seems to bolster the case for that position. In the yeast mechanism theres not selection for a mechanism that actually says, This is the gene I should mutate to solve the problem, said Patricia Foster, a biologist at Indiana University. It shows that evolution can get speeded up.

Hastings at Baylor agreed, and praised the fact that Houseleys mechanism explains why the extra mutations dont happen throughout the genome. You need to be transcribing a gene for it to happen, he said.

Adaptive mutation theory, however, finds little acceptance among most biologists, and many of them view the original experiments by Cairns and the new ones by Houseley skeptically. They argue that even if higher mutation rates yield adaptations to environmental stress, proving that the higher mutation rates are themselves an adaptation to stress remains difficult to demonstrate convincingly. The interpretation is intuitively attractive, said John Roth, a geneticist and microbiologist at the University of California, Davis, but I dont think its right. I dont believe any of these examples of stress-induced mutagenesis are correct. There may be some other non-obvious explanation for the phenomenon.

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I think [Houseleys work] is beautiful and relevant to the adaptive mutation debate, said Paul Sniegowski, a biologist at the University of Pennsylvania. But in the end, it still represents a hypothesis. To validate it more certainly, he added, theyd have to test it in the way an evolutionary biologist wouldby creating a theoretical model and determining whether this adaptive mutability could evolve within a reasonable period, and then by challenging populations of organisms in the lab to evolve a mechanism like this.

Notwithstanding the doubters, Houseley and his team are persevering with their research to understand its relevance to cancer and other biomedical problems. The emergence of chemotherapy-resistant cancers is commonplace and forms a major barrier to curing the disease, Houseley said. He thinks that chemotherapy drugs and other stresses on tumors may encourage malignant cells to mutate further, including mutations for resistance to the drugs. If that resistance is facilitated by the kind of mechanism he explored in his work on yeast, it could very well present a new drug target. Cancer patients might be treated both with normal courses of chemotherapy and with agents that would inhibit the biochemical modifications that make resistance mutations possible.

We are actively working on that, Houseley said, but its still in the early days.

Original story reprinted with permission from Quanta Magazine , an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

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Evolutionary Biologists Probe Long-standing Genetics Mystery – Yale News

Posted: at 5:50 pm

August 17, 2017

Photo credit: Dreamstime

What makes humans different from chimpanzees? Evolutionary biologists from Howard University and the Yale School of Public Health have developed a unique genetic analysis technique that may provide important answers.

Michael C. Campbell, Ph.D., the papers first author and assistant professor in the Howard University Department of Biology, and co-author Jeffrey Townsend, Ph.D., the Elihu Associate Professor in Biostatistics at Yale, published their findings in the journal Molecular Biology and Evolution.

Their methodModel Averaged Site Selection via Poisson Random Field (MASS-PRF)looks at protein-coding genes to identify genetic signatures of positive selection. These signatures are actually DNA changes that contribute to the development of beneficial traits, or human adaptations, that emerged during human evolutionary history and that are shared across the human species.

It’s a quantum leap in our statistical power to detect selection in recently diverged species.

Other approaches have examined this question but analyses have focused on whole genes, typically missing focused evolution that often occurs in small regions of genes. The method Campbell and Townsend created identifies selection within genes, pinpointing sets of mutations that have undergone positive selection.

Our method is a new way of looking for beneficial mutations that have become fixed or occur at 100 percent frequency in the human species, Campbell said. What we are concerned with are mutations within genes and traits that are specific to humans compared to closely related species, such as the chimpanzee. Essentially, we want to know is what are the mutations and traits that make us human and that unite us as a biological species.

Townsend said the technique has far-reaching implications. It helped the research team discover several genes whose evolution appears to have been critical to the divergence of humans from their common ancestor with chimpanzees. The genes play roles in neurological processing, immunity, and reproduction, and the method could eventually help scientists identify many more. It’s a quantum leap in our statistical power to detect selection in recently diverged species, Townsend said.

Campbell began the research project with Drs. Zhao and Townsend while they were associate research scientists in the Department of Biostatistics at the Yale School of Public Health, before he arrived at Howard University in 2015. Dr. Zhao, currently a research scientist at The Jackson Laboratory for Genomic Medicine, co-authored the paper.

This article was submitted by Elisabeth Ann Reitman on August 17, 2017.

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Will Gene Editing Allow Us to Rid the World of Diseases? – Healthline – Healthline

Posted: at 5:50 pm

Scientists recently used a gene-editing tool to fix a mutation in a human embryo. Around the world, researchers are chasing cures for other genetic diseases.

Now that the gene-editing genie is out of the bottle, what would you wish for first?

Babies with perfect eyes, over-the-top intelligence, and a touch of movie star charisma?

Or a world free of disease not just for your family, but for every family in the world?

Based on recent events, many scientists are working toward the latter.

Earlier this month, scientists from the Oregon Health & Science University used a gene editing tool to correct a disease-causing mutation in an embryo.

The technique, known as CRISPR-Cas9, fixed the mutation in the embryos nuclear DNA that causes hypertrophic cardiomyopathy, a common heart condition that can lead to heart failure or cardiac death.

This is the first time that this gene-editing tool has been tested on clinical-quality human eggs.

Had one of these embryos been implanted into a womans uterus and allowed to fully develop, the baby would have been free of the disease-causing variation of the gene.

This type of beneficial change would also have been passed down to future generations.

None of the embryos in this study were implanted or allowed to develop. But the success of the experiment offers a glimpse at the potential of CRISPR-Cas9.

Still, will we ever be able to gene-edit our world free of disease?

According to the Genetic Disease Foundation, there are more than 6,000 human genetic disorders.

Scientists could theoretically use CRISPR-Cas9 to correct any of these diseases in an embryo.

To do this, they would need an appropriate piece of RNA to target corresponding stretches of genetic material.

The Cas9 enzyme cuts DNA at that spot, which allows scientists to delete, repair, or replace a specific gene.

Some genetic diseases, though, may be easier to treat with this method than others.

Most people are focusing, at least initially, on diseases where there really is only one gene involved or a limited number of genes and theyre really well understood, Megan Hochstrasser, PhD, science communications manager at the Innovative Genomics Institute in California, told Healthline.

Diseases caused by a mutation in a single gene include sickle cell disease, cystic fibrosis, and Tay-Sachs disease. These affect millions of people worldwide.

These types of diseases, though, are far outnumbered by diseases like cardiovascular disease, diabetes, and cancer, which kill millions of people across the globe each year.

Genetics along with environmental factors also contribute to obesity, mental illness, and Alzheimers disease, although scientists are still working on understanding exactly how.

Right now, most CRISPR-Cas9 research focuses on simpler diseases.

There are a lot of things that have to be worked out with the technology for it to get to the place where we could ever apply it to one of those polygenic diseases, where multiple genes contribute or one gene has multiple effects, said Hochstrasser.

Although designer babies gain a lot of media attention, much CRISPR-Cas9 research is focused elsewhere.

Most people who are working on this are not working in human embryos, said Hochstrasser. Theyre trying to figure out how we can develop treatments for people that already have diseases.

These types of treatments would benefit children and adults who are already living with a genetic disease, as well as people who develop cancer.

This approach may also help the 25 million to 30 million Americans who have one of the more than 6,800 rare diseases.

Gene editing is a really powerful option for people with rare disease, said Hochstrasser. You could theoretically do a phase I clinical trial with all the people in the world that have a certain [rare] condition and cure them all if it worked.

Rare diseases affect fewer than 200,000 people in the United States at any given time, which means there is less incentive for pharmaceutical companies to develop treatments.

These less-common diseases include cystic fibrosis, Huntingtons disease, muscular dystrophies, and certain types of cancer.

Last year researchers at the University of California Berkeley made progress in developing an ex vivo therapy where you take cells out of a person, modify them, and put them back into the body.

This treatment was for sickle cell disease. In this condition, a genetic mutation causes hemoglobin molecules to stick together, which deforms red blood cells. This can lead to blockages in the blood vessels, anemia, pain, and organ failure.

Researchers used CRISPR-Cas9 to genetically engineer stem cells to fix the sickle cell disease mutation. They then injected these cells into mice.

The stem cells migrated to the bone marrow and developed into healthy red blood cells. Four months later, these cells could still be found in the mices blood.

This is not a cure for the disease, because the body would continue to make red blood cells that have the sickle cell disease mutation.

But researchers think that if enough healthy stem cells take root in the bone marrow, it could reduce the severity of disease symptoms.

More work is needed before researchers can test this treatment in people.

A group of Chinese researchers used a similar technique last year to treat people with an aggressive form of lung cancer the first clinical trial of its kind.

In this trial, researchers modified patients immune cells to disable a gene that is involved in stopping the cells immune response.

Researchers hope that, once injected into the body, the genetically edited immune cells will mount a stronger attack against the cancer cells.

These types of therapies might also work for other blood diseases, cancers, or immune problems.

But certain diseases will be more challenging to treat this way.

If you have a disorder of the brain, for example, you cant remove someones brain, do gene editing and then put it back in, said Hochstrasser. So we have to figure out how to get these reagents to the places they need to be in the body.

Not every human disease is caused by mutations in our genome.

Vector-borne diseases like malaria, yellow fever, dengue fever, and sleeping sickness kill more than 1 million people worldwide each year.

Many of these diseases are transmitted by mosquitoes, but also by ticks, flies, fleas, and freshwater snails.

Scientists are working on ways to use gene editing to reduce the toll of these diseases on the health of people around the world.

We could potentially get rid of malaria by engineering mosquitoes that cant transmit the parasite that causes malaria, said Hochstrasser. We could do this using the CRISPR-Cas9 technique to push this trait through the entire mosquito population very quickly.

Researchers are also using CRISPR-Cas9 to create designer foods.

DuPont recently used gene editing to produce a new variety of waxy corn that contains higher amounts of starch, which has uses in food and industry.

Modified crops may also help reduce deaths due to malnutrition, which is responsible for nearly half of all deaths worldwide in children under 5.

Scientists could potentially use CRISPR-Cas9 to create new varieties of food that are pest-resistant, drought-resistant, or contain more micronutrients.

One benefit of CRISPR-Cas9, compared to traditional plant breeding methods, is that it allows scientists to insert a single gene from a related wild plant into a domesticated variety, without other unwanted traits.

Gene editing in agriculture may also move more quickly than research in people because there is no need for years of lab, animal, and human clinical trials.

Even though plants grow pretty slowly, said Hochstrasser, it really is quicker to get [genetically engineered plants] out into the world than doing a clinical trial in people.

Safety and ethical concerns

CRISPR-Cas9 is a powerful tool, but it also raises several concerns.

Theres a lot of discussion right now about how best to detect so-called off-target effects, said Hochstrasser. This is what happens when the [Cas9] protein cuts somewhere similar to where you want it to cut.

Off-target cuts could lead to unexpected genetic problems that cause an embryo to die. An edit in the wrong gene could also create an entirely new genetic disease that would be passed onto future generations.

Even using CRISPR-Cas9 to modify mosquitoes and other insects raises safety concerns like what happens when you make large-scale changes to an ecosystem or a trait in a population that gets out of control.

There are also many ethical issues that come with modifying human embryos.

So will CRISPR-Cas9 help rid the world of disease?

Theres no doubt that it will make a sizeable dent in many diseases, but its unlikely to cure all of them any time soon.

We already have tools for avoiding genetic diseases like early genetic screening of fetuses and embryos but these are not universally used.

We still dont avoid tons of genetic diseases, because a lot of people dont know that they harbor mutations that can be inherited, said Hochstrasser.

Some genetic mutations also happen spontaneously. This is the case with many cancers that result from environmental factors such as UV rays, tobacco smoke, and certain chemicals.

People also make choices that increase their risk of heart disease, stroke, obesity, and diabetes.

So unless scientists can use CRISPR-Cas9 to find treatments for these lifestyle diseases or genetically engineer people to stop smoking and start biking to work these diseases will linger in human society.

Things like that are always going to need to be treated, said Hochstrasser. I dont think its realistic to think we would ever prevent every disease from happening in a human.

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Cancer Genetics Expert Katherine L. Nathanson, MD, Named Deputy Director of Abramson Cancer Center – Newswise (press release)

Posted: August 18, 2017 at 4:50 am

Newswise PHILADELPHIA Katherine L. Nathanson, MD, an internationally recognized expert in the field of cancer genetics, has been named deputy director of the Abramson Cancer Center of the University of Pennsylvania. Nathanson is a professor of Translational Medicine and Human Genetics in the Perelman School of Medicine, and the associate director for Population Sciences in the Abramson Cancer Center, co-leader of the Cancer Control Program, and Chief Oncogenomics Physician. She also serves as director of Genetics for the Basser Center for BRCA. She will begin her new role as deputy director immediately.

Dr. Nathanson is a distinguished physician-scientist and has long been a valued colleague and member of the cancer center, said Robert Vonderheide, MD, DPhil, the director of the ACC. Her clinical and research portfolio incorporates an impressive array of diseases. She has played a critical role in many of the ACCs most recent advancements and is well known as an international expert in somatic and germline cancer genetics. I am delighted she has accepted this new leadership role.

As Deputy Director, Nathanson will oversee multiple aspects of the cancer centers scientific and clinical missions, including strategic planning, program development and evaluation, faculty recruitment, leadership appointments, and resource allocation.

Im honored to take on this new leadership role to advance the mission of the Abramson Cancer Center: to reduce the burden of cancer throughout the region, the nation, and the world by extending our integrated program of laboratory, clinical and population-based research, Nathanson said.

Nathanson received her bachelors degree from Haverford College and her MD from the University of Pennsylvania. She completed residencies in Internal Medicine at Beth Israel Hospital in Boston, as well as in Clinical genetics at the Childrens Hospital of Philadelphia and at Penn. She joined the Penn faculty in 2001, and since then, she has published more than 250 peer-reviewed articles in top journals, such as Nature, JAMA, Cancer Cell, and The New England Journal of Medicine. She has an extensive record of national service for multiple organizations including the American College of Medical Genetics and Genomics, where she serves as the Cancer Genetics editor for Genetics in Medicine, and the American Association for Cancer Research. Nathanson is also the chair of the Cancer Genetics study section for the National Institutes of Health and is an elected member of the American Society of Clinical Investigation and the American Association of Physicians.

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Penn Medicineis one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and theUniversity of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according toU.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals byU.S. News & World Report– Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

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Idaho dairy industry elevates worker safety, training – Capital Press

Posted: at 4:50 am

Idahos dairy industry is taking a unique and proactive approach to improving worker safety with a statewide on-farm training program.

Carol Ryan Dumas/Capital Press

David Douphrate, assistant professor of epidemiology, human genetics and environmental sciences at the University of Texas, answers questions during a panel on a new worker training program for Idahos dairy industry during the Idaho Milk Processors Association annual conference, while Robert Hagevoort, extension dairy specialist at New Mexico State University, looks on.

SUN VALLEY, Idaho Training a largely inexperienced, non-English-speaking workforce on Idahos dairies for the ultimate goal of worker safety has become a priority for both dairymen and the processors they supply.

Unfortunately, it took a fatality on a dairy to bring it to the table, Rick Naerebout, director of operations for the Idaho Dairymens Association, said during the Idaho Milk Processors Association annual conference last week.

That tragedy occurred in February 2016, when worker Ruperto Vazquez-Carrera, 37, drowned in a waste pond after mistakenly driving a feed truck into the pond in pre-dawn hours under flooded conditions.

IDFA quickly responded to prevent future tragedies by engaging with experts in worker safety and training to figure out how to get our arms around the issue of comprehensive training, Naerabout said.

We realized we have an opportunity to do more than check a box on safety and be proactive instead of reactive, he said.

The worker training and safety program has been in development for more than a year, and IDFA has hired a full-time worker training and safety specialist to lead it. The program rolled out this week, starting at dairies owned by IDA board members.

Processors are collaborating in the program and sharing in the cost, said Daragh Maccabee, senior vice president of procurement and dairy economics for Glanbia Nutritionals.

Processors met with IDA in April 2016 to discuss a path forward, wanting to participate in a meaningful way, he said.

While there are already good practices in place, the event which drew the attention of OSHA, the United Farm Workers of American and the media highlighted a need for more structure. The primary objective of the program is to provide a safe work environment, he said.

People safety is our No.1 priority, and Glanbia wants to support the producer community in a real way, he said.

As an industry, we need to be able to show to the world we are responsible, he said.

IDFA contracted worker safety and training experts David Douphrate, assistant professor of epidemiology, human genetics and environmental sciences at the University of Texas, and Robert Hagevoort, extension dairy specialist with New Mexico State University to develop a program.

Hagevoort said the U.S. dairy industry is experiencing growing pains, with the number of operations decreasing and herd size increasing, driven by economies of scale. It is also moving to automation, with a need for high-skilled workers.

Employment on dairies is not based on skill but on willingness, resulting in a lot of foreign workers unfamiliar with large animals. And its a population challenged by reading comprehension and retention, he said.

Training has to be consistent, repetitive and comprehensive and include both classroom and live training with animals. In addition to the what, the why of safety issues and animal handling must be explained, he said.

Idahos consortium can be beneficial in developing and evaluating training materials and training the trainer to train employees, he said.

Douphrate agreed, saying the focus needs to be on safety leadership and management.

You cant be everywhere on the farm, you have to delegate and need to equip supervisors, he said.

They need to be able to effectively train workers and evaluate whether that training is being retained and workers are applying what they learned, he said.

We want a proactive approach to address injuries and fatalities before they happen, he said.

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Genetic Variance is Key to Individual Immune Response – Genetic Engineering & Biotechnology News

Posted: at 4:50 am

Ever wonder why your friend, co-worker, or partner doesnt get as sick as you, even though they caught the same bug you did? Maybe they made some Faustian bargain that affords them greater protection to infections, or perhaps they are part of some top-secret government experiment that injects them with an array of antigens isolated from an alien race living in Area 51. While both theories are potential explanations, it seems likely that differences in response to infection lie in something a bit more scientificlike genetics. Now, a collaborative team of investigators from the University of Bonn, Germany, and the New York Genome Center has just published findings that map several genetic variants that affect how much gene expression changes in response to an immune stimulus.

Results from the new studypublished in Nature Communications in an article entitled Genetic Regulatory Effects Modified by Immune Activation Contribute to Autoimmune Disease Associationsoffer novel insights into the genetic contribution to varying immune responses among individuals and its consequences on immune-mediated diseases.

Our defense mechanisms against microbial pathogens rely on white blood cells that are specialized to detect infection,” explained co-senior study investigator Veit Hornung, Ph.D., chair of immunobiochemistry at the Ludwig-Maxmilians-Universitt in Munich. Upon encounter of microbes, these cells trigger cellular defense programs via activating and repressing the expression of hundreds of genes.

We wanted to understand how genetic differences between individuals affect this cellular response to infection,” added co-senior study investigator Johannes Schumacher, Ph.D., a research scientist at the Institute of Human Genetics within the University of Bonn.

The human immune system plays a central role in autoimmune and inflammatory diseases, cancer, metabolism, and aging. The researchers discovered hundreds of genes where the response to immune stimulus depended on the genetic variants carried by the individual.

“These genes include many of the well-known genes of the human immune system, demonstrating that genetic variation has an important role in how the human immune system works,” noted lead study investigator Sarah Kim-Hellmuth, Ph.D., a postdoctoral researcher at the New York Genome Center. “While earlier studies have mapped some of these effects, this study is particularly comprehensive, with three stimuli and two-time points analyzed.”

In the current study, the research team captured genetic variants whose effects on gene regulation were different depending on the different infectious state of the cells. These included four associations to diseases such as cholesterol level and celiac disease. Moreover, the researchers discovered a trend of genetic risk for autoimmune diseases such as lupus and celiac disease to be enriched for gene regulatory effects modified by the immune state.

“Here, we isolate monocytes from 134 genotyped individuals, stimulate these cells with three defined microbe-associated molecular patterns (LPS, MDP, and 5-ppp-dsRNA) [lipopolysaccharide, muramyl dipeptide, and 5′ triphosphate double-stranded RNA], and profile the transcriptomes at three-time points, the authors wrote. Mapping expression quantitative trait loci (eQTL), we identify 417 response eQTLs (reQTLs) with varying effects between conditions. We characterize the dynamics of genetic regulation on early and late immune response and observe an enrichment of reQTLs in distal cis-regulatory elements. In addition, reQTLs are enriched for recent positive selection with an evolutionary trend towards enhanced immune response. Finally, we uncover reQTL effects in multiple GWAS [genome-wide association study] loci and showed a stronger enrichment for response than constant eQTLs in GWAS signals of several autoimmune diseases.

Co-senior author Tuuli Lappalainen, Ph.D., assistant professor at Columbia University and core member of the New York Genome Center added that this data supports a paradigm where genetic disease risk is sometimes driven not by genetic variants causing constant cellular dysregulation, but by causing a failure to respond properly to environmental conditions such as infection.”

Using the collected monocyte samples, the researchers treated the cells with three components that mimic infection with bacteria or a virus. They then analyzed how cells from different individuals respond to infection by measuring gene expression both during the early and late immune response. Integrating the gene expression profiles with genome-wide genetic data of each individual, they were able to map how genetic variants affect gene expression, and how this genetic effect changes with the immune stimulus.

Findings from this new study provide a highly robust and comprehensive dataset of innate immune responses and show wide variation among individuals exposed to diverse pathogens over multiple time points. The investigators identified population differences in immune response and demonstrated that immune response modifies genetic associations to disease. The research sheds light on the genomic elements underlying response to environmental stimuli and the dynamics and evolution of immune response.

“It’s been known for a long time that most diseases have both genetic and environmental risk factors, concluded Dr. Lappalainen. But it’s actually more complicated than that because genes and environment interact. As demonstrated in our study, a genetic risk factor may manifest only in certain environments. We are still in early stages of understanding the interplay of genetics and environment, but our results indicate that this is a key component of human biology and disease. The molecular approach that we took in our study can be a particularly powerful way for researchers to delve deeper into this question.”

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Genetic Variance is Key to Individual Immune Response – Genetic Engineering & Biotechnology News

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