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Category Archives: Genome

Genome analysis for reinfection cases in capital – Hindustan Times

Posted: March 31, 2021 at 3:27 am

The decision comes a day after the Centre said it found the presence of a novel variant of Sars-Cov-2 in Delhi in nine samples, while 65 others had the UK variant B.1.1.7.

PUBLISHED ON MAR 26, 2021 04:45 AM IST

Samples of anyone with a past history of Covid-19 who tests positive again, or those who catch the disease after getting two doses of a vaccine, will be mandatorily sent for whole genome sequencing, the Delhi government ordered on Thursday. The decision is aimed at augmenting surveillance to look for any concerning variants.

The decision comes a day after the Centre said it found the presence of a novel variant of Sars-Cov-2 in Delhi in nine samples, while 65 others had the UK variant B.1.1.7. It is yet to be established how the novel variant changes the nature of the virus, but it contains two mutations (E484Q and L452R) that could make it spread more readily or evade the immunity conferred by a past infection or a vaccine. The directorate general of health services (DGHS) directive also said that each district has to send 12 samples (three each of mild, moderate, severe and critical cases) of Covid-19 positive cases per week to the National Centre for Disease Control (NCDC) for whole genome sequencing. This will help us in detecting which strain is causing most of the infections here whether it is the new variant, other variants such as UK, South Africa or Brazil, or something else, said a senior official from Delhis health department.

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Genome analysis for reinfection cases in capital - Hindustan Times

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Precision BioSciences to Participate in the Guggenheim Healthcare Talks 2021 Genomic Medicines & Rare Disease Day – Yahoo Finance

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Bloomberg

(Bloomberg) -- From his perch high above Midtown Manhattan, just across from Carnegie Hall, Bill Hwang was quietly building one of the worlds greatest fortunes.Even on Wall Street, few ever noticed him -- until suddenly, everyone did.Hwang and his private investment firm, Archegos Capital Management, are now at the center of one of the biggest margin calls of all time -- a multibillion-dollar fiasco involving secretive market bets that were dangerously leveraged and unwound in a blink.Hwangs most recent ascent can be pieced together from stocks dumped by banks in recent days -- ViacomCBS Inc., Discovery Inc. GSX Techedu Inc., Baidu Inc. -- all of which had soared this year, sometimes confounding traders who couldnt fathom why.One part of Hwangs portfolio, which has been traded in blocks since Friday by Goldman Sachs Group Inc., Morgan Stanley and Wells Fargo & Co., was worth almost $40 billion last week. Bankers reckon that Archegoss net capital -- essentially Hwangs wealth -- had reached north of $10 billion. And as disposals keep emerging, estimates of his firms total positions keep climbing: tens of billions, $50 billion, even more than $100 billion.It evaporated in mere days.Ive never seen anything like this -- how quiet it was, how concentrated, and how fast it disappeared, said Mike Novogratz, a career macro investor and former partner at Goldman Sachs whos been trading since 1994. This has to be one of the single greatest losses of personal wealth in history.Late Monday in New York, Archegos broke days of silence on the episode.This is a challenging time for the family office of Archegos Capital Management, our partners and employees, Karen Kessler, a spokesperson for the firm, said in an emailed statement. All plans are being discussed as Mr. Hwang and the team determine the best path forward.The cascade of trading losses has reverberated from New York to Zurich to Tokyo and beyond, and leaves myriad unanswered questions, including the big one: How could someone take such big risks, facilitated by so many banks, under the noses of regulators the world over?One part of the answer is that Hwang set up as a family office with limited oversight and then employed financial derivatives to amass big stakes in companies without ever having to disclose them. Another part is that global banks embraced him as a lucrative customer, despite a record of insider trading and attempted market manipulation that drove him out of the hedge fund business a decade ago.A disciple of hedge-fund legend Julian Robertson, Sung Kook Bill Hwang shuttered Tiger Asia Management and Tiger Asia Partners after settling an SEC civil lawsuit in 2012 accusing them of insider trading and manipulating Chinese banks stocks. Hwang and the firms paid $44 million, and he agreed to be barred from the investment advisory industry.He soon opened Archegos -- Greek for one who leads the way -- and structured it as a family office.Family offices that exclusively manage one fortune are generally exempt from registering as investment advisers with the U.S. Securities and Exchange Commission. So they dont have to disclose their owners, executives or how much they manage -- rules designed to protect outsiders who invest in a fund. That approach makes sense for small family offices, but if they swell to the size of a hedge fund whale they can still pose risks, this time to outsiders in the broader market.This does raise questions about the regulation of family offices once again, said Tyler Gellasch, a former SEC aide who now runs the Healthy Markets trade group. The question is if its just friends and family why do we care? The answer is that they can have significant market impacts, and the SECs regulatory regime even after Dodd-Frank doesnt clearly reflect that.Valuable CustomerArchegos established trading partnerships with firms including Nomura Holdings Inc., Morgan Stanley, Deutsche Bank AG and Credit Suisse Group AG. For a time after the SEC case, Goldman refused to do business with him on compliance grounds, but relented as rivals profited by meeting his needs.The full picture of his holdings is still emerging, and its not clear what positions derailed, or what hedges he had set up.One reason is that Hwang never filed a 13F report of his holdings, which every investment manager holding more than $100 million in U.S. equities must fill out at the end of each quarter. Thats because he appears to have structured his trades using total return swaps, essentially putting the positions on the banks balance sheets. Swaps also enable investors to add a lot of leverage to a portfolio.Morgan Stanley and Goldman Sachs, for instance, are listed as the largest holders of GSX Techedu, a Chinese online tutoring company thats been repeatedly targeted by short sellers. Banks may own shares for a variety of reasons that include hedging swap exposures from trades with their customers.Unhappy InvestorsGoldman increased its position 54% in January, according to regulatory filings. Overall, banks reported holding at least 68% of GSXs outstanding shares, according to a Bloomberg analysis of filings. Banks held at least 40% of IQIYI Inc, a Chinese video entertainment company, and 29% of ViacomCBS -- all of which Archegos had bet on big.Im sure there are a number of really unhappy investors who have bought those names over the last couple of weeks, and now regret it, Doug Cifu, chief executive officer of electronic-trading firm Virtu Financial Inc., said Monday in an interview on Bloomberg TV. He predicted regulators will examine whether there should be more transparency and disclosure by a family office.Without the need to market his fund to external investors, Hwangs strategies and performance remained secret from the outside world. Even as his fortune swelled, the 50-something kept a low profile. Despite once working for Robertsons Tiger Management, he wasnt well-known on Wall Street or in New York social circles.Hwang is a trustee of the Fuller Theology Seminary, and co-founder of the Grace and Mercy Foundation, whose mission is to serve the poor and oppressed. The foundation had assets approaching $500 million at the end of 2018, according to its latest filing.Its not all about the money, you know, he said in a rare interview with a Fuller Institute executive in 2018, in which he spoke about his calling as an investor and his Christian faith. Its about the long term, and God certainly has a long-term view.His extraordinary run of fortune turned early last week as ViacomCBS Inc. announced a secondary offering of its shares. Its stock price plunged 9% the next day.The value of other securities believed to be in Archegos portfolio based on the positions that were block traded followed.By Thursdays close, the value of the portfolio fell 27% -- more than enough to wipe out the equity of an investor who market participants estimate was six to eight times levered.Its also hurt some of the banks that served Hwang. Nomura and Credit Suisse warned of significant losses in the wake of the selloff and Mitsubishi UFJ Financial Group Inc. has flagged a potential $300 million loss.You have to wonder who else is out there with one of these invisible fortunes, said Novogratz. The psychology of all that leverage with no risk management, its almost nihilism.(Updates with latest bank to detail exposure in penultimate paragraph.)For more articles like this, please visit us at bloomberg.comSubscribe now to stay ahead with the most trusted business news source.2021 Bloomberg L.P.

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Precision BioSciences to Participate in the Guggenheim Healthcare Talks 2021 Genomic Medicines & Rare Disease Day - Yahoo Finance

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PrecisionLife Continues Growth and Expansion With Acquisition of Danish Genomic Analytics Innovator GenoKey – Business Wire

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OXFORD, England & AALBORG, Denmark--(BUSINESS WIRE)--PrecisionLife today announces that it has acquired its long-term Danish technology development partner GenoKey ApS, bringing together the leaders in combinatorial analytics and large-scale genomic analysis, and enabling PrecisionLife to continue its expansion as an AI-enabled precision medicine company. Financial details of the paper-based transaction were not disclosed.

PrecisionLifes platform, which includes technology developed with GenoKey, enables the company to gain unique insights into genes associated with disease, as biomarkers and as targets for drug discovery. PrecisionLifes business model maximizes the impact of its platform by partnering with others as well as building a pipeline of proprietary assets in chronic diseases.

In addition to its expertise and IP, PrecisionLife will benefit from GenoKeys strong relationships with the Danish health system and leading academic clinical research centers including Aalborg, Aarhus and Copenhagen. Recently, PrecisionLife joined the pan-European FEMaLe consortium led by researchers from Aarhus University, which is a 5.3M international EU Horizon 2020 project that aims to develop precision medicine approaches to improve the diagnosis, treatment and quality of life of patients with endometriosis.

PrecisionLife will maintain its core platform development operations at GenoKeys site in Denmark with further team expansion in the region planned. GenoKeys Chairman and co-founder, Hans-Christian Brahe Mller joins the board of the wholly-owned subsidiary, PrecisionLife ApS. GenoKeys scientific advisors will become part of the PrecisionLife advisory group.

The acquisition of GenoKey solidifies a long-term highly productive collaboration around core IP, and positions PrecisionLife for its next round of investment and growth as a leader in the delivery of precision medicine beyond cancer and rare disease said Dr Steve Gardner, CEO of PrecisionLife.

The accuracy and additional insights generated by PrecisionLifes combinatorial analytics platform have been validated in multiple chronic disease areas such as ALS, schizophrenia, asthma, type-II diabetes and endometriosis as well as severe COVID-19. During the pandemic, PrecisionLife was able to find significantly more signals in severe COVID-19 patient datasets than traditional Genome Wide Association Study (GWAS) methods used by international consortia with access to much larger data sets, uncovering unique avenues for therapeutic intervention (1). These achievements are complimented by GenoKeys collaboration with Professor Erling Mellerup and his team at Copenhagen University on bipolar and other neuropsychiatric disorders, initially sponsored by the Lundbeck Foundation.

Welcoming the transaction, Hans-Christian Brahe Mller, Chairman of GenoKey said, This acquisition presents an exciting opportunity to ensure that GenoKeys 10 years of pioneering analytics development can contribute to the global challenge of delivering new solutions for patients with unmet medical needs in chronic diseases, which represent a huge economic and social burden to healthcare systems and millions of patients around the world.

1. COVID-19 studies, see https://www.medrxiv.org/content/10.1101/2020.06.17.20134015v2.full.pdf and https://www.medrxiv.org/content/10.1101/2021.02.08.21250899v1.full.pdf

About PrecisionLife

PrecisionLife is headquartered near Oxford, UK and has operations in Aalborg and Copenhagen, Denmark, Warsaw, Poland and Cambridge, MA, USA. The companys unique combinatorial analytic platform generates more insights into the complex biology of chronic diseases, driving the next wave of precision medicine applications and finding new treatment opportunities for patients unmet medical needs. PrecisionLife partners with disease charities, clinical research groups, CROs, best of breed technology providers and pharma, biotech and healthcare companies to improve our knowledge of chronic disease biology. PrecisionLife operates an innovation engine that translates proprietary disease biology insights into new drug discovery programs, more successful and cost-effective clinical trials and more personalized clinical decision support tools.

For more information see https://precisionlife.com/

Follow us on LinkedIn (precisionlife) and Twitter (@precisionlifeAI)

About GenoKey ApS

GenoKey was founded by Dr Gert Lykke Mller (now Chief Analytics Officer of PrecisionLife), Hans-Christian Brahe Mller and two colleagues. GenoKey pioneered the underlying mathematical approach that enables deep combinatorial analysis of genomic and other clinical and epidemiological patient data. Gert was the first to reduce this innovative approach to computational practice, and this has been developed in collaboration with PrecisionLife into a powerful analytical platform that enables the largest and most detailed precision medicine studies.

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PrecisionLife Continues Growth and Expansion With Acquisition of Danish Genomic Analytics Innovator GenoKey - Business Wire

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Hong Kong Baptist University-led research unlocks the genomic secrets of organisms that thrive in extreme deep-sea environments – Taiwan News

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HONG KONG SAR - Media OutReach - 29 March 2021 - A study led by scientists at Hong Kong Baptist University (HKBU) has decoded the genomes of the deep-sea clam (Archivesica marissinica) and the chemoautotrophic bacteria (Candidatus Vesicomyosocius marissinica) that live in its gill epithelium cells. Through analysis of their genomic structures and profiling of their gene expression patterns, the research team revealed that symbiosis between the two partners enables the clams to thrive in extreme deep-sea environments.

The research findings have been published in the academic journal Molecular Biology and Evolution.

Due to the general lack of photosynthesis-derived organic matter, the deep-sea was once considered a vast "desert" with very little biomass. Yet, clams often form large populations in the high-temperature hydrothermal vents and freezing cold seeps in the deep oceans around the globe where sunlight cannot penetrate but toxic molecules, such as hydrogen sulfide, are available below the seabed. The clams are known to have a reduced gut and digestive system, and they rely on endosymbiotic bacteria to generate energy in a process called chemosynthesis. However, when this symbiotic relationship developed, and how the clams and chemoautotrophic bacteria interact, remain largely unclear.

Horizontal gene transfer between bacteria and clams discovered for the first time

A research team led by Professor Qiu Jianwen, Associate Head and Professor of the Department of Biology at HKBU, collected the clam specimens at 1,360 metres below sea level from a cold seep in the South China Sea. The genomes of the clam and its symbiotic bacteria were then sequenced to shed light on the genomic signatures of their successful symbiotic relationship.

The team found that the ancestor of the clam split with its shallow-water relatives 128 million years ago when dinosaurs roamed the earth. The study revealed that 28 genes have been transferred from the ancestral chemoautotrophic bacteria to the clam, the first discovery of horizontal gene transfera process that transmits genetic material between distantly-related organisms from bacteria to a bivalve mollusc.

The following genomic features of the clam were discovered, and combined, they have enabled it to adapt to the extreme deep-sea environment:

(1) Adaptions for chemosynthesis

The clam relies on its symbiotic chemoautotrophic bacteria to produce the biological materials essential for its survival. In their symbiotic relationship, the clam absorbs hydrogen sulfide from the sediment, and oxygen and carbon dioxide from seawater, and it transfers them to the bacteria living in its gill epithelium cells to produce the energy and nutrients in a process called chemosynthesis. The process is illustrated in Figure 1.

The research team also discovered that the clam's genome exhibits gene family expansion in cellular processes such as respiration and diffusion that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, the transfer of small molecules and proteins within the symbiont, and the regulation of the endosymbiont population. It helps the host to obtain sufficient nutrients from the symbiotic bacteria.

(2) Shift from phytoplankton-based food

Cellulase is an enzyme that facilitates the decomposition of the cellulose found in phytoplankton, a major primary food source in the marine food chain. It was discovered that the clam's cellulase genes have undergone significant contraction, which is likely an adaptation to the shift from phytoplankton-derived to bacteria-based food.

(3) Adaptation to sulfur metabolic pathways

The genome of the symbiont also holds the secrets of this mutually beneficial relationship. The team discovered that the clam has a reduced genome, as it is only about 40% of the size of its free-living relatives. Nevertheless, the symbiont genome encodes complete and flexible sulfur metabolic pathways, and it retains the ability to synthesise 20 common amino acids and other essential nutrients, highlighting the importance of the symbiont in generating energy and providing nutrients to support the symbiotic relationship.

(4) Improvement in oxygen-binding capacity

Unlike in vertebrates, haemoglobin, a metalloprotein found in the blood and tissues of many organisms, is not commonly used as an oxygen carrier in molluscs. However, the team discovered several kinds of highly expressed haemoglobin genes in the clam, suggesting an improvement in its oxygen-binding capacity, which can enhance the ability of the clam to survive in deep-sea low-oxygen habitats.

Professor Qiu said: "Most of the previous studies on deep-sea symbiosis have focused only on the bacteria. This first coupled clamsymbiont genome assembly will facilitate comparative studies that aim to elucidate the diversity and evolutionary mechanisms of symbiosis, which allows many invertebrates to thrive in 'extreme' deep-sea ecosystems."

The research was jointly conducted by scientists from HKBU and the HKBU Institute for Research and Continuing Education, the Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, City University of Hong Kong, the Japan Agency for Marine-Earth Science and Technology, the Sanya Institute of Deep-Sea Science and Engineering, and the Guangzhou Marine Geological Survey.

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Hong Kong Baptist University-led research unlocks the genomic secrets of organisms that thrive in extreme deep-sea environments - Taiwan News

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A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe – Science Advances

Posted: March 20, 2021 at 2:57 am

INTRODUCTION

Giraffes are immediately recognizable due to their exceptionally long necks and legs, making them the tallest terrestrial animals. Giraffes played a central role in different evolutionary schools of thought, including those of Lamarck and Darwin. Their unusual anatomy is thought to provide various selective advantages. In addition to allowing access to otherwise inaccessible food resources (1), their elevated head position provides an excellent vantage point for scanning the horizon and thus detecting predators or competitors, both of which are crucial for their survival (2). However, their exceptional anatomy is also accompanied by considerable physiological challenges. Most notably, the cardiovascular system has to tolerate twofold higher systemic blood pressure than most other mammals to supply the brain with blood (3). This elevated hydrostatic pressure has resulted in hypertrophy of their cardiac and arteriole walls (3) and adaptations of the circulation system that prevent sudden changes in blood pressure when a giraffe elevates or lowers its head (4). Giraffes also have neuromotor delays due to their long neural networks (5) and face difficulties in rising due to their long legs, which increases the danger associated with resting and drinking. They also require greatly enlarged and strengthened nuchal ligaments to support their long, heavy neck (6). Hence, the giraffe provides a unique case for studying co-adaptation or evolution in several different traits that are causally linked to an extreme body plan.

The okapi (Okapia johnstoni) is the only other extant member of the Giraffidae family and provides a useful point of genomic comparison. A study published in 2016 provided the first giraffe and okapi draft genomes and identified candidate genes and pathways involved in neck elongation and cardiovascular adaptations (7). However, these initial draft genomes were relatively fragmented, which can both introduce certain biases and limit the interpretation of some analyses (8). Furthermore, the comparative analyses carried out using these draft genomes were restricted to 17,210 genes, which were annotated by aligning with cattle (Bos taurus) reference transcripts, thus limiting the resolution power to explore genomic features unique to the giraffe, not least given the paucity of other ruminant genomes available at that time. Hence, the availability of a higher-quality giraffe genome assembly together with our recently published whole-genome dataset for ~50 ruminant species (9) opens up the possibility of identifying giraffe-specific mutations with a much higher accuracy and robustness. This, in turn, provides a better resource for inferring the true genomic changes that account for the unique body plan of the giraffe.

Here, we report an improved, chromosome-level genome assembly of a Rothschilds giraffe (Giraffa camelopardalis rothschildi), the results of comparative analysis against the recently available ruminant genomes, andcruciallyfunctional validation of one key cardiovascular and skeletal gene in gene-edited mice. These results provide insights into the genetic basis of the giraffe anatomy and associated adaptations, with particular implications concerning the cardiovascular system, which may be helpful for treating human cardiovascular disease and hypertension.

We sequenced the genome of a male Rothschilds giraffe with a combination of single-molecule real-time sequencing (using an Oxford Nanopore platform), paired-end sequencing (with an Illumina HiSeq 2000 system), and Hi-C sequencing (figs. S1 and S2 and table S1). First, we used Nanopore data to generate initial contigs, and after polishing with Illumina reads, we obtained an assembly with contig N50 of 35.9 Mb (table S2). Next, Hi-C data were used to anchor the contigs into chromosomes, which yielded a final assembly of 2.44 Gb with ~97.95% of the bases successfully anchored to 15 chromosomes (2n = 30) (figs. S3 and S4 and table S3). A series of evaluations show that the genome assembly is of high quality (see the Supplementary Materials, figs. S2 to S6, and tables S4 to S11).

Chromosome evolution is related to genome size, gene family evolution, and speciation (10). The giraffe has many fewer chromosomes (2n = 30) than the putative ancestral karyotype of even-toed ungulates (2n = 58 to 60), suggesting the occurrence of multiple chromosome fusion events in its evolution (11). Using the genomes of cattle, goat, giraffe, and okapi, with sperm whale as outgroup, we reconstructed the ancestral karyotype of the Giraffidae and Bovidae families (2n = 60) (table S12), which corresponds to the ancestor of the Pecora suborder (11). The results indicate that just three fissions and three fusions occurred in the cattle lineage since the pecoran ancestor. Hence, most of the ancestral chromosome structure is retained in cattle, including the complement of 30 chromosomes. In contrast, a minimum of four fissions and 17 fusions occurred between the pecoran ancestor and the giraffe, resulting in a substantial decrease (to 15) in haploid chromosome number (Fig. 1). The functional significanceif anyof such prolific chromosome fusions in giraffes requires further research.

(A) The figure displays the distribution of ancestral chromosome segments in cattle and giraffe genomes, including interchromosome rearrangements and fission and fusion events in cattle and giraffe. Blue asterisks in the cattle chromosome diagram indicate chromosome fission events in cattle. Blue asterisks in the giraffe chromosome diagram indicate sites of chromosome rearrangements. (B) Circos plot showing syntenic relationships of chromosomes between giraffe (left) and cattle (right). Chromosomes are colored on the basis of the cattle homologies. (C) Two types of collinear relationship between giraffe and cattle. The top and bottom horizontal lines represent giraffe and cattle chromosomes, respectively, and the lines between them link the alignment blocks.

We next evaluated the adaptive divergence between giraffe and other mammals in coding regions, using both the branch and the branch-site models implemented in PAML (12). We detected 101 positively selected genes (PSGs) and 359 rapidly evolving genes (REGs) in the giraffe (P < 0.05 according to 2 tests in both cases) (fig. S7 and tables S13 and S14) (13). This is a large increase compared to those found in the previous giraffe genome study, which identified 17 PSGs and 53 genes with adaptive divergence (high divergence compared with other mammals or unique substitutions) in giraffe (7). Notably, while 7 of the 17 PSGs from the previous study overlapped with our findings, the remaining 10 PSGs showed no positive selection signal in our analyses, which is primarily caused by the inclusion of many more ruminant branches as background. We show two examples of how the inclusion of a larger background panel or better genome quality refined our ability to identify giraffe-specific selection signals (fig. S8). Similarly, only 15 of the 53 previously identified adaptive divergence genes (7) were identified as PSGs or REGs in our analysis. Together, the improved genome assembly (better genome completeness, accuracy, and annotation) and higher number of accessible ruminant reference genomes allow us to substantially decrease both false positive and false negative signals of genes undergoing adaptive evolution in the giraffe. A Gene Ontology (GO) enrichment analysis showed that the 460 PSGs and REGs identified in the present study are primarily related to growth and development, nervous and visual systems, circadian rhythm, and blood pressure regulation (table S15). The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathwaybased analysis suggested that the rapidly evolving pathways in giraffe compared to okapi are related to metabolic, circulatory, and immune systems (table S16).

The giraffe fibroblast growth factor (FGF) receptorlike protein 1 (FGFRL1) gene has previously been identified as one of the most conspicuous targets of selection in the giraffe (7). FGFRL1 contains a cluster of seven nonsynonymous mutations in its key FGF binding domain when compared against sequences in other ruminants and outgroup mammals (fig. S9). Using our substantially expanded set of background genomes, we confirmed that these mutations are unique to the giraffe and that FGFRL1 contains more unique substitutions than any other giraffe gene (table S17). Mutations in FGFRL1 cause severe cardiovascular and skeletal defects in humans and mice (14, 15), and hence we follow Agaba et al. (7) in hypothesizing that FGFRL1 may be associated with the extreme cardiovascular and skeletal adaptations in the giraffe. To investigate the in vivo consequences of these substitutions, we introduced these seven mutations into the FGFRL1 gene of mice to obtain giraffe-type FGFRL1 mice, using CRISPR-Cas9 technology (fig. S10). In contrast to mice with targeted complete deletion of the gene (14), which die with multiple congenital malformations, giraffe-type FGFRL1 mice were viable and fertile.

The cardiovascular hemodynamic in the giraffe is characterized by exceptionally high blood pressure without related organ damage, in contrast to the typical detrimental effects of hypertension observed in other animals/humans (3). FGFRL1 is known to be involved in the cardiovascular system (14), and we hypothesized that some vascular adaptations in the giraffe may only be apparent in a hypertensive physiological setting. To test this, we induced high blood pressure in wild-type (WT) and mutant FGFRL1 mice. The mice were infused with angiotensin II (Ang II; 900 ng/kg per minute; fig. S11), which induces hypertension by vasoconstriction and sodium retention. Our giraffe-type FGFRL1 mice showed no signs of congenital heart defects (fig. S12) or any obvious alterations in heart rate compared to WT controls (fig. S13). Although the basal blood pressure was slightly higher in giraffe-type than in WT FGFRL1 mice, no significant difference was observed (fig. S13). After Ang II infusion for 28 days, the average systolic and diastolic blood pressure in WT controls were significantly increased to 158.97 5.01 and 94.54 8.60 mmHg (Fig. 2A), respectively, confirming that hypertension was successfully induced in them. Unexpectedly, the Ang IIinduced hypertension was absent in giraffe-type FGFRL1 mice, which showed average systolic and diastolic pressures of 125.30 5.97 and 83.43 11.77 mmHg, respectively, after Ang II infusion for 28 days (Fig. 2A), not significantly different from giraffe-type FGFRL1 controls. Moreover, significantly less myocardial and renal fibrosis was observed in giraffe-type FGFRL1 mice, as manifested by significantly lower proportion of collagen fibers in their heart and kidney than in WT controls, which obviously resulted from the absence of Ang IIinduced hypertension in giraffe-type FGFRL1 mice (Fig. 2B and fig. S14). In addition, the impaired heart function caused by hypertension in Ang IItreated WT mice was also significantly alleviated in giraffe-type FGFRL1 mice, as evidenced by improved left ventricular ejection fractions (LVEFs) and fractional shortening (LVFS) (fig. S15). Our findings collectively suggest that the giraffe-type FGFRL1 has little effect on cardiac development but can prevent Ang IIinduced hypertension and thus avoid or at least alleviate a range of detrimental effects of hypertension. In addition, our molecular dynamics (MD) simulations suggested that the unique variants in giraffe-type FGFRL1 could affect its binding affinity with FGF ligands (fig. S16), potentially interfering with their cross-talk with renin-angiotensin-aldosterone system to modulate blood pressure and providing a possible mechanism by which giraffe-type FGFRL1 modulates blood pressure (16). Despite the differences in cardiovascular structure and physiology between mice and human and the possibility that other genes may have contributed to the observed systemic co-adaptation to hypertension, it is intriguing to speculate that FGFRL1 might hold promise as a therapeutic target for prevention or treatment of hypertension or cardiovascular diseases in humans. Nevertheless, we acknowledge that this perspective is tentative and awaits a thorough investigation of the mechanisms behind the observed cardiovascular effect of giraffe-type FGFRL1.

(A) Giraffe-type FGFRL1 mice showed significantly lower systolic, diastolic, and mean arterial pressures (mmHg) than WT FGFRL1 mice after Ang II infusion for 28 days. *P < 0.05, **P < 0.01, ***P < 0.001, one-way ANOVA followed by Tukeys post hoc test. (B) Giraffe-type FGFRL1 mice had significantly lower proportions of fibrotic areas in heart than WT FGFRL1 mice after 28 days of Ang II infusion. ***P < 0.001, one-way ANOVA followed by Tukeys post hoc test. Error bars indicate SD. (C) Whole-mount skeletons of P0 mice showed hypoplasia of skeletal elements in giraffe-type FGFRL1 mice. **P < 0.01 by t test. (D) Adult giraffe-type FGFRL1 mice show no discernible body size and skeletal phenotype difference to WT mice. (E) Giraffe-type FGFRL1 mice showed significantly higher BMD, BV/TV, and average trabeculae thickness than WT mice. *P < 0.05, **P < 0.01 by t test. Photo credit: Jianbo Gao, The Fourth Military Medical University.

In addition to the observed cardiovascular effect, we noticed that postnatal day 0 (P0) giraffe-type FGFRL1 mice showed prenatal hypoplasia of skeletal elements, with a smaller body size, delayed craniofacial development, shortened axial/appendicular skeletons, and smaller vertebral lengths than the P0 WT mice (Fig. 2C and fig. S17). In contrast, adult giraffe-type FGFRL1 mice (24 to 26 g, 16 weeks) showed no discernible skeletal phenotype compared with WT mice or any significant deviation in body size and weight, limb length, or vertebral height (Fig. 2D and fig. S18). This suggests that mutations in this gene in itself are not sufficient for neck elongation in the giraffe, refuting a previous hypothesis (7), although again we must recognize the limitations of introducing a gene into a different genetic background. However, it also shows that giraffe-type FGFRL1-associated postnatal bone growth can compensate for the observed prenatal effects such that FGFRL1 may play an indirect role in the exceptional bone growth of giraffe, e.g., by accelerating bone formation to maintain bone mineral density (BMD), as in humans (17). Therefore, we next examined bone ultrastructure by micro computed tomography (microCT). Giraffe-type FGFRL1 mice achieved significantly higher BMD, bone volume/total volume (BV/TV) ratio, and average trabeculae thickness in vertebrae (C3) and distal femur (Fig. 2E and fig. S19). Skeletal growth rate tends to be inversely related to bone strength in animals (18), but despite having the highest skeletal growth rate among mammals, giraffes maintain normal BMD (19). In summary, we find indications for a pleiotropic adaptive effect of the highly unique giraffe-type FGFRL1 by not only significantly enhancing hypertension resistance but also achieving normal bone strength, despite the accelerated rate of bone growth in the giraffe.

Previous anatomical and physiological analyses suggest that multiple giraffe organs are involved in associated adaptations of the cardiovascular system, including hypertrophy of the left ventricle and interventricular walls (3), thickening of blood vessels of the lower extremities, and low glomerular filtration rates (20). Our results revealed that several pathways involving tissues influenced by high blood pressure, such as blood vessels, heart, and kidney, were significantly diverged between giraffe and other ruminants (table S16). The platelet activation pathway plays an important role in hypertension-associated thrombosis (Fig. 3A) (21). Three REGs (COL1A2, LYN, and PLCB1) and a number of genes with giraffe-specific amino acid variations are involved in the two major platelet activation, shape change, and platelet aggregation paths. A further set of PSGs and REGs that participate in phosphatidylinositol metabolism (PIP4K2A, ISYNA1, MTMR3, CDS1, and INPP1) may also be involved in the regulation of platelet activation (22). Another giraffe-divergent pathway is the adrenergic signaling pathway in cardiomyocytes, which is related to cardiac contraction and possibly the morphological remodeling of the giraffe heart (Fig. 3B) (23). Highly divergent genes in this pathway are mainly involved in ion transport (SCN7A, SLC9A1, ATP1A4, and CACNA2D4), which is important for myocardial function (24). We also found strong signals of adaptation in two major adrenergic receptors (ADRA1A and ADRA2B), as previously reported (7). Although ADRA2B is mainly expressed in the nervous system, both of these receptors are strongly related to blood pressure regulation (25, 26). Last, we detected strong giraffe-specific divergence in genes related to the proximal tubule bicarbonate reclamation and endocrine and other factor-regulated calcium reabsorption pathways. Changes in these pathways may reduce the pressure gradient across membranes in the giraffe kidney and protect it from hypertensive damage (Fig. 3C) (20). The REG AQP1 encodes a water-transporting protein in cell membranes of kidney proximal tubules and is involved in kidney development and injury responses (27). Two REGs (PLCB1 and ATP1A4) that are reportedly involved in hypertension or related organ damage participate in more than one of the mentioned pathways (28, 29), in accordance with expectations of co-adaptation of the blood vesselheartkidney axis in giraffe. In addition to genes in the mentioned pathways, we also detected other PSGs and REGs that may help to avoid hypertensive damage, including ANGPTL1, which is associated with the integrity of vascular endothelium (30), and TGFB1, which is strongly implicated in multiorgan fibrosis associated with hypertension (31). The finding of multiple genes involved in several phenotypic traits that share evolutionary constraints due to the extreme stature of the giraffe suggests that pleiotropy may play an important role in evolving such an extreme body plan.

(A) Modifications of genes in the platelet activation pathway may help to prevent damage to giraffe blood vessels. (B) Genes in the adrenergic signaling in cardiomyocytes that show high divergence in giraffe. (C) The proximal tubule bicarbonate reclamation (top) and endocrine and other factor-regulated calcium reabsorption (bottom) pathways may help to prevent kidney damage.

For herbivorous ungulates subject to predation, vigilance is crucial for survival and has two components: gathering information and instigating muscular action after signal transduction through the nervous system (32). Giraffes are thought to have a distinctive retinal cone topography that provides the best visual acuity in the Artiodactyla, which, together with the elevated head, enhances the capacity for horizon scanning (33). Accordingly, we found not only a number of PSGs and REGs that contribute to eye development and vision but also a number of genes that are related to Usher syndrome in humans (CDH23, PCDH15, USH2A, NINL, and UBR3), which affects vision, hearing, and balance (34), suggesting a related suite of sensory co-adaptations in giraffe (Fig. 4A). Similar to all other ruminants, we found only two opsin genes; thus, we could not verify that giraffes see color, at least not trichromatic color as has been hypothesized before (35). We found indications that the sense of smell in the giraffe may be degenerated. Compared to okapi, giraffe has lost at least 53 olfactory-related genes, including 50 encoding olfactory receptors, two encoding vomeronasal receptors, and one encoding an odorant binding protein (table S18). Further analysis shows that most of these olfactory receptors are spatially clustered and were lost because of a segmental deletion (Fig. 4B and figs. S20 and S21). Moreover, the contracted gene families in giraffe were also enriched in olfactory receptor activity (fig. S22 and tables S19 and S20). This may be an evolutionary consequence of enhanced vision, consistent with the hypothesized trade-off in sensory acuity found in many taxa (36) and/or with reduction in competition for food with other browsers.

(A) PSGs and REGs associated with giraffes visual, auditory, and balance systems. (B) Giraffes have lost several olfactory receptors (for example, on chromosome 10 of goat) compared to okapi. The location of genes on goat chromosome is shown in the rectangle, and the collinear relationship of giraffe-goat and okapi-goat is shown in the top and bottom panels, respectively. (C) Genetic changes involved in light-mediated regulation of the molecular clock in giraffe suprachiasmatic nucleus (SCN) neurons.

Moreover, the extreme morphology of the giraffe increases its vulnerability when asleep by increasing the time required to become upright. Expectedly, therefore, given their needs for vigilance and high food intakes, giraffe sleep durations are among the lowest recorded (37). Concordantly, we found evidence of rapid evolution of PER1 in giraffe, a period family gene critical for the maintenance of circadian rhythm (38) and the emergence of a stop codon in the first exon of PER2 (Fig. 4C and fig. S23), possibly altering the transcript of this important circadian rhythm gene. HCRT, which plays a role in the regulation of sleep and arousal (39), also shows accelerated evolution in giraffe. Together, there is evidence that adaptive modifications of circadian rhythm and sleep arousal systems in giraffe have promoted short and fragmented sleep patterns. Overall, the comparative genomic analysis highlights that the unique stature of the giraffe has led to a series of necessary behavioral co-adaptations.

Procedures applied in sample collection and animal experiments were reviewed and approved by the Institutional Ethics Committee of the Northwestern Polytechnical University and Fourth Military Medical University. Fresh blood samples of a male Rothschilds giraffe used for genome sequencing were acquired during a routine physical examination at the Guangzhou Zoo in China. High-quality genomic DNA was extracted using a Qiagen DNA purification kit, then used to construct libraries, and sequenced with Illumina HiSeq and Oxford Nanopore GridIOn platforms. Data (199.64 and 140.56 Gb) were obtained, after filtering, from these platforms. In addition, lymphocytes collected from the same blood sample were used for Hi-C library construction, and 138.71-Gb data were obtained using the Illumina HiSeq X Ten platform.

Contigs were assembled by Wtdbg software (v1.2.8) (41), and the assembled contig-level genomes were polished by Racon (v1.2.1) (42) and Pilon (v1.22) (43). Last, the contigs were anchored into chromosomes by Hi-C sequencing reads through the Juicer (version 1.5) (44) and 3D-DNA (version 180922) (45) software workflow. To further improve the chromosome-scale assembly, it was subjected to manual review and refinement using Juicebox Assembly Tools (https://github.com/theaidenlab/juicebox). Last, genome quality was estimated with BUSCO (version 3.0.2) (46), whole-genome synteny with cattle (UMD3.1) genome, and k-mer analysis and by mapping back the initial reads to the assembly.

According to the good genome synteny with cattle genome (Fig. 1B), we assigned the chromosome numbers of our assembly as indicated by previous research (11). Our assembly agrees with the giraffe karyotype revealed before: 13 biarmed autosomal pairs and an acrocentric autosomal pair plus the sex chromosomes (47). Then, we mapped both the Nanopore reads and Illumina reads used for the assembly back onto it. More than 98% of the Nanopore raw reads could be mapped to the assembly properly with an average depth of 54, and 99.99% of genome has a reads depth more than 50, with chromosome X excluded (fig. S5 and table S4). Furthermore, 97.14% of the Illumina reads could be mapped to the genome properly with an average depth of 79 (fig. S5 and table S5). Last, the assembly also recovered 96.15% of the expected single-copy orthologous genes according to BUSCO analysis (table S6), the highest coverage yet for the reported Giraffidae genomes (table S7).

Tandem repeats were predicted by Tandem Repeats Finder software (v4.04) (48). RepeatMasker (open-4.0.7) (49), RepeatModeler (v1.0.8) (49), and RepeatProteinMask (v1.0.8) were used together to predict transposable elements. Gene structures were determined by combining ab initio and homology methods. For ab initio annotation, we used Augustus (v3.2.1) (50) and GENSCAN (v1.0) (51) to analyze the repeat-masked genome. For homolog-based annotation, protein sequences of cattle (B. taurus; ensemble 87 release), sheep (Ovis aries; ensemble 87 release), and human (Homo sapiens; ensemble 87 release) genomes were aligned to giraffe sequences using BLAST software (v2.3.0) (52) and GeneWise (v2.4.1) (53). Then, results from the three methods were integrated by EVidenceModeler software (v1.1.1) (54). To annotate the gene functions, the integrated gene set was aligned against public databases, including KEGG, Swiss-Prot, TrEMBL, COG, and NR with BLAST (v2.3.0) (52), and merged with annotations by InterProScan (v4.8) (55) software. The integrity of annotation was estimated by comparison with reference genome annotations and BUSCO (version 3.0.2) (46). On the basis of homology and ab initio gene prediction, we annotated 21,580 protein-coding genes in the genome (fig. S6 and tables S8 to S11), with 96.81% completeness according to BUSCO analysis, suggesting that our annotation also has high quality (table S6).

The complete mitochondrial cytochrome b (Cytb) gene (1140 base pairs) was used to investigate the phylogenetic status of our sample. In addition, previously published cytb sequences of 160 giraffes and outgroup (okapi and pronghorn) were retrieved from the National Center for Biotechnology Information (NCBI) according to the accession number provided by a research before (56). These sequences were aligned with our data using ClustalW in MEGA7 (57) with default parameters and subsequently adjusted manually to maximize positional homology. Last, the remaining sequences were used to infer the phylogenetic tree using IQ-TREE (58) under parameters -nt AUTO -m MFP -bb 1000 -bnni -o Pronghorn. As a result, the specimen used for genome sequencing was clustered together with the giraffe subspecies Rothschilds giraffe (G. camelopardalis rothschildi) with high support (ultra fast bootstrap value = 93).

We reconstructed the ancestral chromosome karyotype of Giraffidae and Bovidae families using the genomes of cattle, goat, giraffe, okapi, and sperm whale (as outgroup). With giraffe as the reference genome, we carried out pairwise alignments with other species as target using LASTZ (v1.1) with parameters T=2 C=2 H=2000 Y=3400 L=6000 K=2200 --format=axt. Then, axtChain, chainMergeSort, chainPreNet, and ChainNet were used to generate chain and net files as input for DESCHRAMBLER (59). Last, we identified 1502 conserved segments by DESCHRAMBLER at a 300-kb resolution and reconstructed 30 predicted ancestral chromosomes (2n = 60) with a total length of ~2.25 Gb.

To minimize effects of annotation, pseudogenes, and genome quality, we used conserved genome synteny methodology to establish a high-confidence orthologous gene set that included four nonruminants (human, dog, horse, and pig) and six ruminants (pronghorn, giraffe, okapi, forest musk deer, reindeer, and cattle). Using the goat genome sequence (ARS1) as a reference, we performed synteny alignment for these ten species with Last (version 894) (60) and generated pairwise whole-genome alignments with Multiz (version 11.2) (61) using the default parameters. A total of 13,776 genes were extracted from the synteny alignments. We used the Codeml program in the PAML package (version 4.8) (12) to estimate the lineage-specific evolutionary rate for each branch with the phylogenetic extracted from a ruminant study before (9). First, the branch-site model was used for detecting PSGs. The giraffe lineage was specified as the foreground branch, and a likelihood ratio test (LRT) was conducted to examine whether the branch-site model containing positively selected codons (omega > 1) fits better than the null model, which only includes neutral selection or negative selection (omega 1). The P values for model comparison were computed based on chi-square statistics. Besides, the potential positive selection of codon sites was assessed by their posterior probabilities calculated with the Bayes empirical Bayes (BEB) method. The genes with an LRT P < 0.05 and with the sites with a posterior probability of positive selection over 0.95 from the BEB method were treated as PSGs. Then, the branch model that was used for detecting REGs used the same orthologous genes as above. We tested whether the foreground branch (the giraffe lineage) exhibited a significantly higher omega (regardless of whether it is greater than 1) than the background branch (the other lineages) using the LRT test. The genes with an LRT P < 0.05 were treated as REGs in giraffe. The combined set of PSGs and REGs was subjected to KEGG and GO enrichment analysis (P < 0.05) with the online tool Metascape (v1.0) (62).

We used 12 species to construct gene families, including human, horse, dog, pig, killer whale, camel, pronghorn, giraffe, okapi, white-lipped deer, forest musk deer, and cattle. Proteins with premature stop codons, nontriplet codon lengths, and fewer than 30 amino acids were removed. Last, we used OrthoMCL (v2.0.9) (63) for protein clustering with a dataset of 256,596 protein sequences. Family expansion or contraction analysis was performed by CAFE (v3.1) (64), and the phylogenetic tree was extracted from the ruminant study before (9). Gene expansion and contraction results for each branch of the phylogenetic tree were estimated, and enrichment analysis about the gene families expanded or contracted in giraffe was performed with KOBAS (v3.0) (65).

For each KEGG pathway with more than 20 genes, we counted numbers of nonsynonymous and synonymous mutations between giraffe and its most recent common ancestor (Nh and Sh, respectively). We also counted numbers of nonsynonymous mutations and synonymous mutations between okapi and the MCRA (Nt and St, respectively). We formulated a null hypothesis that the probabilities of nonsynonymous mutations compare to synonymous mutations in giraffe and okapi are similar and then applied a one-sided binomial test to identify rapidly evolving pathways with significantly more nonsynonymous mutations than expected. The binomial test included three parameters for each KEGG pathway: the number of successes (Nh), the number of trials (Nh + Sh), and the hypothetical probability of success is given by Nt*All_NhAll_NtNt*All_NhAll_Nt+St*All_ShAll_St, where All is the genome-wide value. Last, the rapidly KEGG pathways were identified using a threshold of P < 0.05 (one-sided binomial test).

Through analysis of conserved genome synteny with goat, we obtained a highly confident set of orthologous genes of mammals (including mouse, human, cat, cheetah, dog, rhinoceros, horse, camel, pig, dolphin, killer whale, and sperm whale) and 51 ruminant species. Domain regions of the encoded proteins were predicted with Pfam (67). Then, we scanned the domain regions in the syntenic alignments and identified the giraffe-specific amino acid substitutions compared to all other species. The substitutions that were not fixed in all published giraffe genomes were further filtered. Last, we identified 414 giraffe genes that have unique substitutions in domain regions, of which 33 genes have more than three unique substitutions (table S17).

The Illumina short reads of giraffe and okapi were mapped onto the cattle genome (UMD3.1). For every gene, the read depth was counted with SAMtools (68) along the coding sequence (CDS). For the CDS region, if more than 50% of the sites had not been mapped with reads in the giraffe, but if more than 50% sites had been mapped with more than 10 reads in okapi, the gene was assumed to be specifically lost in giraffe. It turned out that giraffe uniquely lost 83 genes compared to okapi. To avoid sequencing problem in one research and validate the result, we repeated the same analysis with previously published genomic short reads of another giraffe (9), and it showed that giraffe uniquely lost 78 genes with 63 genes overlapping the result before. However, okapi lost only 13 genes uniquely under the same analysis. We noticed that 53 of the 63 genes lost in giraffe were related to the sense of smell and that they located spatially clustered on chromosomes 10 and 15 on cattle genome (table S18). Furthermore, to validate the result on genome level and to avoid the influence of using cattle genome, we checked the synteny alignment between giraffe-goat (ARS1) and okapi-goat (ARS1), and it verified again that giraffe lost more olfactory-receptor genes on chromosomes 10 and 15 of goat (Fig. 4B and fig. S20). We further checked the deletions on giraffes chromosome 7 (chromosome 10 of goat) with the long Nanopore reads mapped back to the giraffe genome and goat genome; the deletion region can be finely span in giraffe (fig. S21).

Because the 3D structure of the complexes of FGFR1 (a major FGF receptor and was thought to be involved in FGFRL1 signaling) and FGF23 (the ligand) has been revealed (69), we built an in silico 3D structure model of the giraffe FGFRL1 (from IG-II to IG-III domain) by homolog modeling and docked the model with FGF23 to assess possible effects of the mutations on the proteins interaction. The 3D structure model of mtFGFRL1 (seven sites in giraffe type) and WT FGFRL1 (seven sites changed to common type) was separately generated with homolog modeling methods by PROMALS3D (70) with several FGFR structures as templates [Protein Data Bank (PDB) nos. 1E0O, 1EV2, 1II4, 1IIL, 1NUN, 1RY7, 2FDB, 3GRW, 3OJ2, 3OJV, 4J23, and 5W59]. The FGF23 structure was obtained from PDB no. 5w21. The structure of FGFRL1 and FGF23 complexes was produced by the Rosetta (71) protein docking program, using the docking conformation of FGFR1 and FGF23 in PDB no. 5w21 as the initial docking pose.

MD simulations were performed by using the Amber (version 18) software (72) in combination with the ff14SB (version 1.0) force field (73). Protein systems were solvated in the TIP3P water model with an edge distance of 12 , and systems were neutralized (pH 7) by adding suitable counterions (Na+ or Cl). Before performing MD simulations, each system was minimized by means of the steepest descent and conjugate gradient methods through 2000 steps. NPT (constant number of atoms, pressure, and temperature) simulations were then carried out to heat the system from 0 to 300 K using Langevin dynamics for temperature control and the SHAKE algorithm on hydrogen atom constraint. MD simulations were run for 100 ns with the time step set to 2 fs. Last, determination of the relative binding free energy was performed using the molecular mechanics generalized Born surface area method in the Amber package (version 18) (72).

To elucidate the giraffe-type FGFRL1 genes role in skeletogenesis and the cardiovascular system, the seven unique substitutions in giraffe-type FGFRL1 were introduced into the FGFRL1 gene in mice (giraffe-type FGFRL1 mice) by CRISPR-Cas9mediated genome editing as follows. First, single-guide RNA (sgRNA) expression constructs were prepared, based on the pUC57-sgRNA expression vector (no. 51132; Addgene), using oligonucleotide sequences listed in table S21. Next, the sgRNA expression plasmids were linearized and prepared as templates for in vitro transcription using a MEGAshortscript kit (Ambion, AM1354). The sgRNA was purified using a MEGAclear kit (Ambion, AM1908). Fertilized eggs were injected with a mixture of Cas9 protein, sgRNAs, and homologous DNA template. Genomic DNA was then extracted from the tails of 7-day-old mice (new pups) using phenol-chloroform and recovered by alcohol precipitation to detect the mutations. Polymerase chain reaction primers for targeting sites are listed in table S22. Last, mice with expected mutations were mated with WT mice to get enough heterozygous mutant mice, and then homozygous mutant mice were produced by crossing and prepared for consequence experiments.

Neonates (P0) were subjected to whole-mount skeletal staining. Briefly, both P0 WT FGFRL1 (n = 5) and giraffe-type FGFRL1 (n = 5) mice were fixed in 90% ethanol for 12 hours at 4C. Next, specimens were transferred into acetone for 12 hours at room temperature and then into a cartilage staining solution containing 0.03% Alcian blue (w/v; Sigma-Aldrich, USA), 80% ethanol, and 20% acetic acid overnight. The samples were washed with 20% acetic acid, and the ossified tissues were stained in a solution with 0.005% Alizarin red (w/v) overnight at 4C. The specimens were transferred into 1% KOH (w/v) until the muscle tissue was transparent and then saved with 50% glycerol solution containing 1% KOH (w/v). Whole skeleton images were then obtained with an M205 FA stereoscopic microscope (Leica, Germany), and ImageJ software (version 1.46; National Institutes of Health, USA) was used to obtain the following measurements: head length (distance from the frontal tip of the maxilla to the caudal tip of the occipital bone in lateral view), spine length (distance from the annular vertebrae to the tail root), and length of limbs (distance between the two tips of limbs). The measurements were repeated three times for each sample, and average values were obtained.

Adult (16 weeks, 24 to 26 g) WT FGFRL1 mice (n = 8) and giraffe-type FGFRL1 mice (n = 8) were randomly selected and anesthetized by intraperitoneal 1% (w/v) sodium pentobarbital solution (40 mg/kg). The body weight and length (from nose to tail root) of each mouse was measured. Then, x-ray images of the head, lumbar vertebra, and limbs of both sets of mice (n = 3) were acquired using a SkyScan 1276 high-resolution in vivo x-ray microtomography (Bruker, Germany). Digital images were obtained under identical imaging conditions using the same acquisition parameters, and ImageJ software was used to obtain the following measurements: head length (as defined above), height of the L1 lumbar vertebra (distance between the upper and lower endplates of the vertebral body), and length of limbs (as defined above). The measurements were repeated three times for each sample, and average values were obtained.

After x-ray imaging, the adult WT FGFRL1 mice (n = 10) and giraffe-type FGFRL1 mice (n = 10) were sacrificed by an intraperitoneal pentobarbital (Sigma-Aldrich, USA) overdose. The skeleton of each mouse was harvested and fixed by 4.0% formalin. The formalin-fixed femurs and cervical vertebrae were scanned, reconstructed, and analyzed using a GE-LSP industrial microCT system (GE Healthcare, Chicago, IL, USA) with the following parameters: 80 kV, 80 A, and 3.0-s exposure time per projection. The BMD, average trabeculae thickness, and BV/TV of the distal femur (n = 6) and C3 vertebra (n = 10) were measured. In addition, the maximum transverse diameter, average thickness of cortical bone, and both inner and outer perimeters of their femurs (at mid-diaphysis) were measured.

Hypertension was induced using Ang II (Sigma-Aldrich, USA) delivered using Alzet-1004 osmotic mini-pumps (Cupertino, CA). Briefly, WT FGFRL1 and giraffe-type FGFRL1 mice (16 weeks old, 24 to 26 g) were anesthetized with isoflurane (1% at 1.5 liters/min oxygen). A 1-cm incision was then made on the back, and an osmotic mini-pump containing Ang II (n = 10) or an equivalent volume of vehicle (saline, n = 10) was embedded. Ang II (900 ng/kg per minute) was infused at a rate of 10 l/hour for 28 days. At the end of the infusion, the systolic, diastolic, and mean arterial blood pressures were measured using a tail-cuff sphygmomanometer. In addition, cardiac function was evaluated by echocardiography, and hypertension-related cardiac remodeling was examined histologically.

Blood pressure was measured using a BP2010A intelligent noninvasive sphygmomanometer for mice (Softron, Japan), which was calibrated and validated before recording. The reliability of tail-cuff determination of mouse blood pressure was independently validated by radiotelemetry before making critical assessment in mice. Before measurement, mice were acclimated to a restraint box and tail-cuff inflation in a quiet area with designated temperature (22 2C) for 5 days. On the day of testing, mice typically remained relatively calm and still in the restrainer after acclimation period. The tail-cuff was positioned at the base of the tail and a heating pad, supplied as an accessory for the tail-cuff sphygmomanometer, and was preheated to 35C. Blood pressure recordings were acquired after the mice had prewarmed for 10 min. Briefly, the cuff was inflated to 250 mmHg and deflated over 20 s. Ten inflation and deflation cycles were included for each recording. The first three cycles were regarded as acclimation cycles and not included in the analysis. The highest and lowest values in the remaining seven cycles were discarded, and the remaining five readings were averaged for a single session value in further analysis. Changes in tail volume were detected by the pressurized receptor when the blood returned to the tail during cuff deflation. Measurements of the mice were obtained for 3 consecutive days before the Ang II or control treatment to obtain their baseline blood pressure.

Transthoracic echocardiography was performed to evaluate cardiac function using a Vevo 2100 instrument (VisualSonics, Canada) equipped with a 18- to 38-MHz MS-400 imaging sensor. Briefly, the mice were anesthetized with 1% isoflurane via an anesthetic gas machine and maintained in a supine position with limbs fixed, and body temperature was kept stable through a heat pad, while respiration and heart beats were continuously monitored. M-mode images were analyzed to obtain estimates of LVEF, LVFS, left ventricular posterior wall thickness at end diastole, and left ventricular internal diameter at end diastole. For this analysis, a dedicated software (Vevo 2100 version 1.4, VisualSonics, Canada) was used.

At the end of Ang II infusion, the heart (n = 6) and kidney (n = 8) of each vehicle- and Ang IItreated mouse were harvested and fixed with 4.0% formalin (Sigma-Aldrich, USA). Histological sections, 5 m thick, were prepared following standard fixation, clearing, dehydration, waxing, and paraffin-embedding procedures. Representative histological slides were used for histological staining, as follows.

Hematoxylin and eosin staining. The heart and kidney sections were processed by routine dewaxing in xylene followed by hydration with an ethanol concentration gradient. Thereafter, nuclei and cytoplasm in the sections were stained by hematoxylin and eosin (G1004; Servicebio, China), respectively. The sections were then dehydrated, cleared, and mounted. Staining was observed, and images were captured using a BX53+R6 light microscope (Olympus, Tokyo, Japan).

Masson trichrome staining. Heart and kidney tissues were subjected to Masson trichrome staining using a kit and protocols provided by the manufacturer (Sigma-Aldrich, USA). Heart and kidney fibrosis were then measured in terms of the proportion of collagen using ImageJ software. Three randomly selected regions of identical size in each heart or kidney slice were examined, and the average values obtained from them were recorded.

Sirius red staining. The heart sections were stained by incubation in a 0.1% (w/v) solution of Sirius red (G1018; Servicebio, China) in saturated aqueous picric acid for 1 hour. The slides were then washed, dehydrated, and mounted. This treatment stains collagen and noncollagen components red and orange, respectively. Heart fibrosis was measured in terms of the proportion of red-colored collagen using ImageJ software. Three randomly selected regions of identical size in each heart slice were examined, and the average values obtained from them were recorded.

Measurements of continuous variables were expressed as means SD. All statistical analysis was performed with SPSS software (version 19.0; Chicago, USA). Independent Students t tests were used to compare baseline values of WT FGFRL1 and giraffe FGFRL1 mice groups. One-way analysis of variance (ANOVA) was used to compare mean values. If there was a significant overall difference among groups, then Tukeys post hoc test was used for multiple comparisons between groups. A value of P < 0.05 was considered statistically significant.

Acknowledgments: We thank D. Wu for providing the giraffe sample. Funding: This study is supported by the Talents Team Construction Fund of Northwestern Polytechnical University (NWPU) to Q.Q. and W.W., the National Program for Support of Top-notch Young Professionals to Q.Q., the Research Funds for Interdisciplinary Subject, NWPU (19SH030408) to Q.Q., the 1000 Talent Project of Shaanxi Province to Q.Q. and W.W., the National Natural Science Foundation of China (81972052, 81672148, and 81802143) to J.H., and the Independent Research Fund Denmark (8049-00098B) to R.H. Author contributions: Q.Q., J.H., W.W., and R.H. designed this project and research aspects. Zhipeng Li, H.S., G.L., and Q.L. performed sample collection, and D.C. performed sequencing library construction. C.L., L.C., Yuan Yuan, Y.Z., T.Q., M.H., B.Z., Chenglong Zhu, C.Z., and K.W. performed data analysis including genome assembly, annotation, gene family, gene loss, and chromosome evolution. J.G., L.M., and X.C. conducted the experiments for mice. Zihe Li and Y.X. built 3D modeling of proteins. L.Z., Zeshan Lin, Yuan Yin, and W.X. contributed to figure designing. C.L., Q.Q., and J.H. wrote the manuscript. W.W., R.H., and M.T.P.G. performed manuscript amending. Competing interests: J.H., Q.Q., J.G., C.L., and W.W. are inventors on a patent application related to this work filed by the Fourth Military Medical University and the Northwestern Polytechnical University (no. 2020110969712, filed on 14 October 2020). The authors declare no other competing interests. Data and materials availability: All sequencing data and assembled genome have been deposited on the NCBI database with accession ID PRJNA627604. All other data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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A towering genome: Experimentally validated adaptations to high blood pressure and extreme stature in the giraffe - Science Advances

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USask Scientists Help Find the Key to Decoding Rye Genome – Seed World

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An international team led by the IPK Leibniz Institute in Germany and including University of Saskatchewan (USask) researchers has succeeded in completely decoding the genome of rye, despite its large size and complexity.

Rye is a distinctly climate-resistant cereal plant that is of considerable importance for Germany and northeastern Europe. In Canada, most rye is grown in Saskatchewan and Manitoba.

At USask, the research team includes professor Curtis Pozniak, director of USasks Crop Development Centre and Ministry of Agriculture Strategic Research Program Chair in Durum and High-Yield Wheat Breeding and Genetics, plant molecular geneticist Andrew Sharpe, director of Genomics and Bioinformatics at USasks Global Institute for Food Security (GIFS), Sean Walkowiak (Pozniaks former research officer, now research scientist for Canadian Grain Commission), bioinformatics analyst Brook Byrns, and plant sciences emeritus professor Brian Fowler.

Rye is one of the most cold-tolerant cereal crops and can survive the harshest winters typical of the Canadian Prairies, says Pozniak. The genome sequence of rye points to important genes that could be used to enhance the cold tolerance of other important winter crops, including wheat.

The results published today in the journalNature Geneticsare promising for both science and breeding. Rye offers access to a diverse gene pool, not only for rye breeding but also for wheat breeding.

The delivery of the rye genome represents the work of a large and dedicated group of partners across the world, says Sharpe. These results are significant, as they provide a complete genome that is closely related to other grass crop species such as wheat and barley, thus allowing a deeper insight into the evolutionary relationships between them.

All the research data is available to the general public, meaning the extensive genetic diversity of rye can be systematically discovered and used by breeders in a more targeted approach.

The comparatively low economic importance on a global scale, combined with the great complexity of the genome, interfered with rye getting into the focus of the international research community and thus its genome sequence has been revealed only recently, explains professor Nils Stein, lead of the research group Genomics of Genetic Resources at IPKand holder of a joint professorship at the University of Gttingen.

Rye shares a close and long evolutionary history with barley and wheat. However, its role as an important crop is much shorter. While barley and wheat were domesticated about 10,000 years ago in the so-called Fertile Crescent of the Near East, rye initially spread to Northern Europe as a weed growing in barley and wheat fields. Gradually, rye adopted the characteristics of its two big brothers before becoming a purely cultivated species 5,000-6,000 years ago.

There are important biological differences between rye and its two relatives: rye is fertilized through cross-pollination, thus individual genetic traits cannot be fixed as easily as in a self-fertile plant species, and the rye genome is highly complex, which is mainly due to the large number of highly repeated DNA segments.

Knowing the reference sequence makes it easier to transfer positive properties of rye, such as resistances, to wheat without negatively affecting baking properties, for example.

For example, resistance genes from rye can be transferred to wheat through classical cross-breeding, which has already been used repeatedly in the past, says Stein. Sothe significance of our research extends far beyond rye.

The technical prerequisites for sequencing such a complex genome are available today, Stein emphasizes.

The research used homozygous seeds from the plant breeding company KWS SAAT SE & Co. KGaA.

Thenew genome sequence of our inbred line Lo7 is a great technological achievement and an important step forward towards a more comprehensive genetic characterisation of this crop, says Andres Gordillo, lead of rye breeding at KWS.

It will considerably enhance breeding progress and, therefore, the attractiveness of rye. More specific, it will substantially improve our ability to link resistance traits observed in the field with their underlying genes and their location on the rye genome.

Parallel to the work of the international research team led by Stein, Chinese researchers created a reference sequence of a Chinese landrace.

We worked very well with our Chinese colleagues, which ultimately brought great added value for rye breeding and research. We were able to use two different methods to study two very different rye varieties, of which the complete reference sequences are now available, says Stein.With these two studies, rye has caught up with barley and wheat and is in the middle of the genome research era.

Source: University of Saskatchewan

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The global genome sequencing market by revenue is expected to grow at a CAGR of over 9% during the period 20212026 – GlobeNewswire

Posted: at 2:56 am

New York, March 18, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Genome Sequencing Market - Global Outlook and Forecast 2021-2026" - https://www.reportlinker.com/p06036817/?utm_source=GNW

The global market is expected to grow due to the growing number of rare, terminal, and complex diseases, especially cancer. The constant increase in cancer cases is proportionately increasing the number of sequencing-based diagnostics and treatment options in the market. The introduction of single-cell sequencing technology performs advanced sequencing, thereby helping in cell mapping of tumor cells. This technology is widely used in several tumor researches and has been significantly beneficial for developing new diagnostic and anti-tumor treatment methods. The single-cell analysis has become a standard application both in basic and translational research. This technology is widely used in the field of reproductive and embryonic medicine. It can sequence and quantify the whole genome of germ cells and embryonic cells at the single-cell level, thereby helping researchers to understand the occurrence of germ cells.

The following factors are likely to contribute to the growth of the genome sequencing market during the forecast period: Increase in Demand for Single Cell Sequencing Introduction of Portable Genome Sequencing Devices The emergence of Nanopore, Third Generation Genome Sequencing Platform

The study considers the genome sequencing markets present scenario and its market dynamics for the period 2020?2026. It covers a detailed overview of several market growth enablers, restraints, and trends. The report offers both the demand and supply aspects of the market. It profiles and examines leading companies and other prominent ones operating in the market.

Global Genome Sequencing Market Segmentation The global genome sequencing market research report includes a detailed segmentation by product, application, end-user, geography. The steady rise in the sale of high-end consumables in commercial laboratories, research institutes, academic institutes, and large pharma and biotech companies performing a high volume of sequencing-based processes is a significant factor responsible for the growth of consumables. In 2020, the consumables segment accounted for the largest share in the market with 81%. The recurring application of consumables to perform a wide range of sequencing-based studies and diagnostics is another critical factor for high sales for consumables. Moreover, increased preference for array-based genotyping consumables for a wide range of analysis, disease-related mutations, and genetic characteristics associated with cancer research is further expected to increase the demand for consumables during the forecast period. High innovations and the introduction of high throughput advanced technologies are likely to drive the application of sequencing devices. These devices are capable of sequencing million to billion reads in a single run in less time.

New cancer cases are expected to reach 24 million by 2030, which is likely to augur well for oncology genome sequencing growth. As cancer prevalence is growing, the need for effective patient stratification is driving research efforts to identify biomarkers and develop companion diagnostics. Genome sequencing has opened new ways of studying cancer-related conditions. Cancer sequencing using next-generation sequencing (NGS) methods provides more information in less time compared to traditional single-gene and array-based approaches. Hence, NGS technology has the potential to change the future of oncology and deliver personalized medicine. They have revolutionized the diagnosis and treatment of acute myeloid leukemia (AML) with accurate testing, classification, and the ability to take advantage of precision medicine.

The presence of several research institutes and stand-alone genomic laboratories in the US, the UK, Germany, France, and China is a major factor responsible for the growth of genome sequencing devices. To develop personalized and effective new therapies that restore mobility, enhance the quality of life, and improve surgical outcomes for patients with multiple disorders, these centers perform extensive research on sequence structural levels of genomics. Hence, the increased focus on unraveling genetic components of common and complex diseases, including cancer diagnostics, neurological disorders, infectious diseases, and rare childhood disorders, influences the market.

Product Consumables Sequencers & Software Application Oncology Reproductive Health Complex Disease Research Microbial Research Others End-user Academic & Research Institutes Pharma & Biotech Companies Consumer Genomic Service Providers Government & Commercial Laboratories Others

INSIGHTS BY GEOGRAPHY North America and Europe are the largest genome sequencing market across the globe. They are the leading countries to increase the usage of genome sequencing-based healthcare and diagnostics. The US is the largest revenue contributor to the North American market. The advanced healthcare infrastructure and the increased awareness have slowly increased genome sequencing and cell and gene therapies technology penetration. Multiple initiatives for human genome projects in the US have improved patients flow seeking treatment for several terminal and genetic diseases. With advances in technology and the increased demand for personalized treatment, the US genomic sequencing market is poised for growth. The increased awareness among European patients drives the application of personal genome sequencing testing, especially for reproductive health. There is an increased number of consumer genomic service providers in the market.

Geography North America o US o Canada Europe o UK o Germany o France o Italy o Spain APAC o China o India o Japan o South Korea o Australia Latin America o Mexico o Brazil o Argentina Middle East & Africa o Saudi Arabia o Turkey o South Africa o UAE

INSIGHTS BY VENDORS Illumina, Thermo Fisher Scientific, F. Hoffmann-La Roche, BGI, Pacific Biosciences, Oxford Nanopore Technology are the major vendors in the market. The market is competitive and is evolving with the introduction of new technologies in the market. Several companies are developing or commercializing products, expanding their manufacturing facilities, partnering with others in the market. For instance, in 2020, Illumina introduced software for whole-genome analysis to examine rare diseases. Similarly, Thermo Fischer scientific has made a strategic partnership with First genetics JCS to promote NGS in Russia. The Oxford Nanopore technology, nanopore-based sequencing, and Pacbios SMRT technology-based sequencing revolutionize genome sequencing by reducing cost and increasing throughput, attracting end-users to shift from conventional sanger methods to advanced methods in the market.

Prominent Vendors Illumina Thermo Fisher Scientific Oxford Nanopore Technology Pacific Biosciences F. Hoffmann-La Roche BGI

Other Prominent Vendors PerkinElmer Siemens Healthineers Qiagen Macrogen Myriad Intrexon Bioinformatics Biomatters Cytiva 10x Genomics MGI Tech New England Biolabs DNASTAR Beckman Coulter VEROGEN Bio-Rad

KEY QUESTIONS ANSWERED 1. What technological advances are the genome sequencing market observing? 2. What is the growth rate of the genome sequencing market during the forecast period? 3. How the outbreak of the COVID-19 pandemic affect the genome sequencing market? 4. Which regions are likely to hold the largest revenue share during the forecast period? 5. Which end-user segment accounted for the largest market share in 2021?Read the full report: https://www.reportlinker.com/p06036817/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The global genome sequencing market by revenue is expected to grow at a CAGR of over 9% during the period 20212026 - GlobeNewswire

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WANdisco grants industry leading LiveData Platform to fast-track high-volume genome analysis and Covid-19 research in South Korea – PRNewswire

Posted: at 2:56 am

SAN RAMON, Calif., March 17, 2021 /PRNewswire/ -- WANdisco, the LiveData company, announced today that it donated its LiveData Platform to help Korea Research Institute of Bioscience & Biotechnology conduct faster analysis in its efforts towards Covid-19 research. Using the automated data migration and replication platform, the institute has been able to replicate files between Hadoop-based big data clusters and Linux-based analysis clusters 13 times faster than before, and reduce analysis time by over 30 percent.

In early 2020, WANdisco announced free access to their suite of cloud migration and big data tools for teams involved in research and developing potential treatments and cures for the Covid-19 pandemic. WANdisco provided its LiveData Platform along with technical resources to Korean Bioinformation Center (KOBIC)to assist the organization in enhancing its architecture, developing products, and introducing WANdisco's automated replication technology into KOBIC's workflow.

"Donating our LiveData platform to the Covid-19 research was absolutely the right thing to do," said David Richards, Chairman and CEO, WANdisco. "Every minute, new data is being generated about people suffering from Covid-19. Velocity has become more important than anything else in the development of vaccines and treatments to overcome infectious diseases. We were grateful for the opportunity to assist Korea accelerate its Covid-19 research and analysis."

KOBICprovides Bio-Express, a cloud service free to bio-engineering researchers at Korean hospitals, businesses, universities, and research institutes for large-capacity genome analysis and storage. Since March 2020, the platform's Covid-19 research information portalhas provided Covid-19-related genomes and proteomic data from around the world. As the amount of data and users skyrocketed last year, so did the time to replicate terabytes of data between the Hadoop Distributed File System (HDFS) and the Linux/Unix based Lustre file system to support the analysis tools within different operating environments. More than 40 percent of Bio-Express's total processing time was solely dedicated to replicate an average of 20TB of data per day.

Upon hearing about Korea's data replication challenges, WANdisco donated its LiveData Platform to reduce large-scale data replication time while ensuring data availability and consistency to researchers. KOBIC administrators could easily and immediately move HDFS data to Bio-Express with automated migration and replication capabilities. No changes were required to applications, cluster or node configuration or operation while ensuring data changes were replicated completely and consistently.

With this new capacity, KOBIC expects to significantly increase the next generation of Bio-Express's efficiency to perform large-scale genome analysis in 2021. WANdisco has since provided KOBIC with an ongoing license to LiveData Platform alongside technical support to help enhance its architecture, developing products, and applying automated replication into the workflow.

"KOBIC uses the WANdisco live data platform to automate file transfer 13 times faster in both directions between Hadoop-based Big Data Analysis Program Execution Cluster (HDFS) and Linux-based Genomic Analysis Program Execution Cluster (Lustre)," said Kun-Hwan Ko, Researcher at KOBIC Computational Development Team. "We were able to reduce the overall average time to analyze user genomic data of Bio-Express service by more than 30 percent."

About WANdisco

WANdisco is the LiveData company. WANdisco solutions enable enterprises to create an environment where data is always available, accurate and protected, creating a strong backbone for their IT infrastructure and a bedrock for running consistent, accurate machine learning applications. With zero downtime and zero data loss, WANdisco LiveData Platform keeps geographically dispersed data at any scale consistent between on-premises and cloud environments allowing businesses to operate seamlessly in a hybrid or multi-cloud environment. For more information on WANdisco, visit http://www.wandisco.com.

About KOBIC

The Korea Bioinformation Center (KOBIC) is a national bio-resource information center for general management of domestic bio-resource information and research in the field of bioinformation. KOBIC helps domestic research institutes, hospitals, companies, and universities to research genomic data and Covid-19 for free. One of KOBIC's main missions is to develop and operate a system that can analyze large-scale genomic data using the state-of-the-art information technology.

Media Contact:

Josh TurnerSilicon Valley Communications[emailprotected]+1 (917) 231-0550

SOURCE WANdisco

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Centre asks states to focus on genome testing to track mutated virus – Mint

Posted: at 2:56 am

NEW DELHI: As the total number of covid-19 cases caused by mutant variants of coronavirus mounted to 400, centre on Friday, the Centre asked states to follow up on sending samples for genome testing to track circulating virus variants of concern.

All states and Union territories have been tagged to 10 national laboratories under the Indian SARS-CoV-2 Genomics (INSACOG) consortium with National Centre for Disease Control (NCDC) as the nodal institute, the Union health ministry said. The Indian government has recently confirmed circulation of UK, South Africa and Brazil mutant variants of coronavirus in the country.

Also Read | Vaccine utilization rates lower in states witnessing second wave

Public health experts have said that as the mutant strains continue to increase the disease burden, the government needs to look at the diagnostics more closely. Analysing power as well as the density of sequencing ability will be important for India. We need to update our regulatory processes as well for the same and these modifications can be quickly brought to fruition. The US FDA guidelines have provided a relatively easy guideline for achieving the same. Countries need to be alert and create diagnostic kits for the future depending on the presence of mutations," said professor N.K. Ganguly, president, Jawaharlal Institute of Post Graduate Medical Education and Research, and former director general of the Indian Council of Medical Research (ICMR). Ganguly suggested that booster shots in the existing vaccines can be given to neutralise the effects of mutations alongside a few other vaccines.

The Centre has also advised states/UTs to improve testing in districts reporting reduction in testing and increase the overall share of RT-PCR tests (more than 70%), especially in districts dependent on high levels of antigen testing in line with the Test Track & Treat strategy of the government.

While the covid-19 vaccination is progressing in the country administering over 40 million doses to immunise people against the highly infectious disease, Indias covid-19 burden continues to increase. According to the Union health ministry data, some states in the country are reporting a surge in the daily new covid-19 cases. Maharashtra, Punjab, Karnataka, Gujarat and Chhattisgarh together account 80.63% of the daily new cases.

Over 39,726 new daily cases were reported in the last 24 hours, the highest this year. Maharashtra continues to report the highest daily new cases at 25,833, 65% of the daily cases. It is followed by Punjab with 2,369 cases, while Kerala reported 1,899 new cases. The country also recorded over 156 deaths.

Indias total active caseload stood at 2.71 lakh (2,71,282) on Friday, 2.82% of the total positive cases in the country. This is a net incline of 18,918 cases recorded from the total active caseload in the last 24 hours, the government data showed. Three states of Maharashtra, Kerala and Punjab account for 76.48% of Indias total active cases.

Meanwhile, the Central government has also advised states and UTs to carry out an average close contact tracing of a minimum of 20 persons per positive case (in the first 72 hours) along with isolation and early treatment of the serious cases as per clinical protocol. It is also advised to focus on surveillance and stringent containment of those areas in selected districts which are seeing a cluster of cases and focus on clinical management in districts reporting higher deaths," the Union health ministry said in a statement.

States/UTs have been asked to limit the gathering in public places along with promoting covid-appropriate behaviour through communication and enforcement, and accelerate vaccination for priority population groups in districts reporting higher cases. Accelerating the pace of vaccination has also been stressed upon, the Central government said.

Recently, the Centre had deputed high-level public health teams to Maharashtra and Punjab to assist in covid-19 control and containment measures in view of the recent spike in cases in these states.

The Centre had earlier deputed high-level teams to Maharashtra, Kerala, Chhattisgarh, Madhya Pradesh, Gujarat, Punjab, Karnataka, Tamil Nadu, West Bengal, as well as Jammu and Kashmir to support them in their fight against the recent spike in covid-19 cases.

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North America Digital Genome Market Report 2021: Continuous Funding by the Manufacturers and Government in the Field of Genomics – Forecast to 2028 -…

Posted: at 2:56 am

Dublin, March 15, 2021 (GLOBE NEWSWIRE) -- The "North America Digital Genome Market 2021-2028" report has been added to ResearchAndMarkets.com's offering.

North America market for digital genome is expected to rise with a CAGR of 9.75%

The United States dominates North America's genome editing market. The high rate of adoption of advanced technology, the presence of big industry names, high funds for genomic research are all factors attributable to the major share of the country in this market.

Further, extensive research activities in genomics, gene editing, cell line culture, and modification are being conducted, which is boosting the market growth in the US. Several globally-renowned manufacturers of DNA sequencing technologies, equipment, and platforms are active in the US.

For instance, several prominent names in the DNA sequencing industry, such as Thermo Fisher Scientific, Illumina, and others have their corporate presence in the nation, and the enhanced adoption of DNA sequencing has led to a rise in the creation of genomic databases like Ensembl Human Genome Server, UCSC Human Genome Browser Gateway, and others. These factors are projected to drive the digital genome market in the US.

In addition, factors like growing awareness of DNA sequencing, and its applications in different fields, including personalized medicine, clinical diseases, agri-genomics, and others, are contributing to market progress.

COMPETITIVE OUTLOOK

Some of the companies present in this market include Oxford Nanopore Technologies Ltd, Inscripta, Agilent Technologies Inc., Bio-Rad Laboratories Inc., Becton Dickinson and Company (BD), Pacific Bioscience, and Abbott Laboratories.

Key Topics Covered:

1. North America Digital Genome Market - Summary

2. Industry Outlook2.1. Porter's Five Forces Model2.2. Impact of Covid-19 on Digital Genome Market2.3. Market Attractiveness Index2.4. Vendor Landscape2.5. Key Insights2.6. Key Drivers2.6.1. Proliferating Burden of Chronic Diseases2.6.2. Continuous Funding by the Manufacturers and Government in the Field of Genomics2.7. Key Restraints2.7.1. Security Risks Associated With Digital Genome2.7.2. Lack of Skilled Professionals in the Field of Genome Technology2.8. Key Opportunities2.8.1. Technological Advancements2.8.2. Prevailing Awareness in the Developing Economies Regarding Dna Sequencing Technologies

3. Digital Genome Market Outlook - by Product3.1. Sequencing and Analyzer Instruments3.2. Dna/Rna Analysis3.3. Sequencing and Analysis Software3.4. Sequencing Chips3.5. Sample Prep Instruments

4. Digital Genome Market Outlook - by Application4.1. Diagnostics4.2. Drug Discovery4.3. Academic Research4.4. Personalized Medicine4.5. Agricultural4.6. Other Applications

5. Digital Genome Market Outlook - by End-User5.1. Diagnostics and Forensic Labs5.2. Academic Research Institutes5.3. Hospitals5.4. Other End-Users

6. Digital Genome Market - North America6.1. Country Analysis6.1.1. The United States6.1.2. Canada

7. Company Profile7.1. Qiagen Nv7.2. Oxford Nanopore Technologies Ltd7.3. Becton, Dickinson, and Company (Bd)7.4. Illumina Inc7.5. Thermo Fisher Scientific Inc7.6. Pacific Bioscience7.7. Bio-Rad Laboratories Inc7.8. F. Hoffmann-La Roche7.9. Perkinelmer Inc7.10. Regeneron Pharmaceuticals7.11. Biomerieux Sa7.12. Abbott Laboratories7.13. Agilent Technologies Inc.7.14. Inscripta

8. Research Methodology & Scope

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/jweemt

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