Category Archives: Genetics

Genetics

Diversifying the pack: Cross fostering helps Mexican wolf population boost genetic mix – Arizona Daily Star

The center has led the Mexican wolf cross-fostering program that began in 2014. Founded in 1971, it sits on 63 isolated, wooded acres, designed to match the cold, silent and humanless habitat where Mexican wolves live.

Through cross-fostering, 8- to 14-day-old pups born in captivity are placed in a den of similar-aged wild pups in remote areas of the Southwest.

Being able to take puppies from facilities like the Endangered Wolf Center and sneaking them into wild litters is a great way for us to be able to get new genetics out into the wild to help keep that wild population healthier, said Regina Mossotti, director of animal care and conservation at the Endangered Wolf Center.

Mexican wolves breed in April and May, leaving a narrow window for cross-fostering.

To successfully cross-foster a wolf pup, officials must identify a wild wolf that has given birth about the same time that a female wolf in captivity at the center gives birth.

When that does happen, the clock starts ticking.

We have to be able to find a flight, the weather has to work and we have to have enough people to do it, Mossotti said. So all these things, these logistics have to come together to make it happen.

Once the team from the Endangered Wolf Center arrives in Arizona, Game & Fish employees join them on a hike to a specific wolf den, often hidden in the rugged terrain along the Arizona-New Mexico state line.

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Diversifying the pack: Cross fostering helps Mexican wolf population boost genetic mix - Arizona Daily Star

Genetics

A Tiny Difference in Genetics is Good News for Salmon Conservation – The Triplicate

Biologists and anglers alike have long considered spring and fall run Chinook salmon to be different animals due to variations in fat content, maturity and appearance. But a recent study sheds new light on how Chinook (or king) salmon are genetically quite similar and why this may help the native salmon population in the Klamath River.

In a recent study published in the journal Science, HSU Fisheries Biology Professor Andrew Kinziger, HSU graduate student James Hearsey, and their colleagues from NOAA, UC Santa Cruz, and Colorado State University compared billions of DNA bases, the DNA building blocks (e.g., A, T, C, and G), in spring and fall Chinook salmon to see where they differed. To their surprise, they found a minute variation between spring and fall salmon on chromosome 28, in a single small region, known as the Region of Strongest Association or RoSA, that determines when fish migrate upriver.

Our result was extraordinary because we expected the genetic underpinnings to involve many genes, each with a small effect, but what we found was incredibly simple a single small genomic region that determines whether the fish migrates in spring or fall, says Kinziger. Its a total win for conservation.

The findings provide strong evidence that spring and fall Chinook salmon are a single species, despite clear differences in run-timing, fat content, size, and spawning locations.

To expand their data set, the researchers partnered with the Yurok Tribe to analyze the genetics of a Chinook salmon fishery in the Klamath River estuary. They found that the RoSA could be used to almost perfectly predict the date Chinook salmon enter the Klamath River, with a cut-off date of about August 1. The research highlights the strong role of genetics.

Each Chinook salmon inherits two genetic variants (or alleles) from their parents. Chinook salmon that possess two copies of the early allele (EE homozygous) all enter the Klamath River before August 1, whereas those with two copies of the late allele (LL homozygous) enter after this date. Individuals that are a mix of both genotypes (EL heterozygous) had intermediate migration times. It follows that if two heterozygous parents were to mate their offspring would be a mixture of EE homozygous (spring), LL homozygous (fall), and EL heterozygous individuals.

Just like in humans, where brothers and sisters can have different colored eyes, a pair of Chinook salmon parents could produce offspring that are a mixture of spring and fall fish, explains Kinziger.

The research has put a spotlight on the importance of migration run timing as the key trait that defines spring and fall salmon. The data from the study shows that the RoSA genotype explains 85% of the variation in salmon migration patterns.

Kinziger explains that the studys findings could have a profound impact on future conservation projects to restore salmon runs on the Klamath River.

Chinook salmon are currently divided into 17 groups for conservation; nine of these are listed as threatened or endangered under the Endangered Species Act. The Klamath River is home to one of the largest Chinook salmon runs on the west coast and supports important commercial, recreational, and tribal fisheries.

Over the past 100-150 years, Chinook salmon runs on the Klamath have declined precipitously due the construction of dams, overfishing, and habitat degradation. Spring Chinook salmon have been the hardest hitthe upper Klamath River population is extinct, and the number of adults returning to wild areas in other parts of the Klamath River is estimated at 100s-1000s fish, with additional supplementation from hatcheries.

But Kinziger explains that their recent study indicates that spring-run Chinook salmon are potentially less threatened than scientists had thought. By surveying thousands of Chinook salmon from northern California and southern Oregon, the researchers found that the early allele was widespread in salmon populations with suitable habitat.

An important repository of the early allele in the Klamath Basin is the Trinity River Hatchery, which releases millions of spring Chinook salmon every year. Over time, hatcheries have come to be seen in a negative light, however, in this case the Trinity River Hatchery appears to have played a role in retaining the early allele in the Klamath-Trinity Basin, says HSU Professor Emeritus David Hankin, who has worked on salmonid management for over 35 years. I think we can chalk that up as a positive impact of hatchery operations.

The study also reframes the outlook for restoring spring-run salmon to the upper Klamath River where four impassable dams are slated for removalone of the largest habitat restoration efforts in history. Among the many groups who have advocated to let the Klamath River run wild again, the Yurok Tribe stands to see their way of life restored with the return of native salmon runs.

A big question remains in how to bring back spring salmon to the upper Klamath River, once the dams are removed. The new research may provide guidance, explains Kinziger.

The researchers found that the descendants of extirpated Klamath River spring Chinook salmon are still present, suggesting that a historically accurate replica of the spring-run might be regenerated in the Klamath. Once suitable habitat exists in the upper Klamath, the researchers believe that the early allele can repopulate naturally; alternatively, fisheries management programs could jumpstart the process with help from hatcheries by stocking fish with the early allele in the upper Klamath population.

Our findings provide a new perspective and offer paths for achieving this incredibly important goal that means so much, environmentally and culturally, to the North Coast, says Kinziger.

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A Tiny Difference in Genetics is Good News for Salmon Conservation - The Triplicate

Genetics

How do we feed a growing population in a changing climate? – The John Innes Centre

Every minute the world loses 23 hectares of arable land, yet every day there are 160,000 more mouths to feed.

We take for granted an abundance of affordable produce year-round, but it comes at high cost to wildlife and soil due to high-intensity agricultural practices.

As such, we must secure and increase yields in a sustainable way if we are to supply enough food to feed the world. But, how do we feed a growing population in a changing climate?

One potential part of the solution is to develop resilient crop varieties. This of course raises another question; how can we achieve this increased resilience in crops?

New John Innes Centre Group Leader Dr Sanu Arora is working on just that, so we asked her what her group will be doing?

The focus of my research lab is to explore the natural diversity of the Pisum (pea) species for environmental resilience.

Pea is an important place to start because the demand for pea protein is expected to grow exponentially in the coming years, but that is at odds with peas highly volatile yields.

There are many factors causing this yield volatility, such as biotic and abiotic stresses and sub-par agronomic potential. My group will work towards understanding the genetic basis underlying these stresses, with the objective of achieving yield stability.

Well start by looking for genetic sources of resistance to devastating diseases of pea (root rots, powdery and downy mildews) against which the current control strategies are not particularly effective.

Wild pea relatives and landraces are more resilient to changing environment because of their inherent diversity; this is in contrast to the modern crop varieties which went through a genetic bottleneck during domestication followed by intensive breeding.

Before being given the opportunity to start my own group on a Ben Gill Translational Fellowship funded by the John Innes Foundation, I was a Postdoctoral Scientist in the Dr Brande Wulff lab. While there, I developed a new method, dubbed AgRenSeq, to tap into the genetic diversity of crop landraces and wild relatives for disease resistance. This method combines association genetics with resistance gene enrichment sequencing on a genetically diverse panel.

I demonstrated the efficiency of AgRenSeq by cloning four stem rust resistance genes from a diversity panel of Aegilops tauschii, the D genome progenitor of bread wheat. Ill continue this project within my new group, helping make it a smooth transition.

Subsequently, this approach has been adapted to other crop diversity panels, including Watkins wheat landrace collection and now the John Innes Centres own Pisum collection.

Before joining the John Innes Centre, I studied for my my PhD at the Punjab Agricultural University in India. My PhD project explored the genetic diversity present in Ae. tauschii for agronomic and nutritional traits. It was during my PhD that I first realised the enormous potential of the wild wheat relatives in wheat enhancement as well as the huge challenges in the way of tapping that potential.

Growing up in Punjab, India, I closely witnessed the transformative potential of science in agriculture as my region developed into the bread-basket of the country because of the Green revolution. Because of this, I have always associated science with its application in agriculture. Therefore, it is no surprise that I ended up as a crop scientist.

I feel fortunate to be working in crop genetics in this era, when we are on the cusp on another green revolution, which will be powered by the new genomic technologies.

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How do we feed a growing population in a changing climate? - The John Innes Centre

Genetics

Latin American Patients with Lung Cancer and Native American Ancestry See Increased EGFR Mutations – Cancer Network

Genomic and ancestry analyses published in Cancer Discovery revealed that among patients with lung cancer from Latin America, Native American ancestry was associated with increased mutations in the EGFR gene, independent of smoking status.1

Researchers indicated that these findings suggest that germline genetics, rather than environmental disparities, underlie these observed disparities.

Lung cancer is the leading cause of cancer mortality, both in the United States and globally, and understanding inherited risk factors for this disease may help us to identify populations that would benefit from increased screening efforts, Matthew Meyerson, MD, PhD, director of the Center for Cancer Genomics at Dana-Farber Cancer Institute in Boston, said in a press release.2

To explore the landscape of somatic cancer mutation in lung cancers from Latin America and to evaluate the influence of germline ancestry of genetically amalgamated patient populations on these somatic alterations, the study investigators performed genomic analysis of 601 lung cancer cases from Mexico and 552 from Colombia, including 499 self-reported non-smokers. Next-generation sequencing targeting a panel of 547 cancer genes plus intronic regions of 60 cancer genes was used to identify single nucleotide variants (SNVs), indels, somatic copy number alterations (SCNAs), and gene fusions; importantly, this gene panel covered all currently known lung cancer drivers.

It was discovered that 48% of all samples harbored oncogenic mutations in EGFR, KRAS, BRAF, ERBB2, or MET, or fusions in ALK, ROS1, or RET. Moreover, 785 of 1153 samples harbored at least 1 detectable alteration in a broader set of known lung cancer driver genes also including TP53, STK11, KEAP1, SMARCA4, SETD2, MYC, and MDM2. The detected mutation frequencies of EGFR and KRAS were 30% and 10%, respectively, in the tested lung cancer samples from Mexican patients, and 23% and 13%, respectively, in the tested lung cancer samples from Colombian patients.

Using a new method developed by Jian Carrot-Zhang, PhD, and Alexander Gusev, PhD, ancestry analyses from the tumor samples was also performed in this admixed population of patients. Further, global ancestry analysis was performed to measure proportions of African, European, and Native American ancestry across the genome. In addition, local ancestry analysis was performed, which evaluates genetic ancestry at a particular chromosomal location.

After obtaining data on both somatic alteration and genetic ancestry, the next step for the researchers was assessing the correlation of these features. After adjusting for various factors, including self-reported smoking status and sample-specific tumor mutational burden, it was discovered that global Native American ancestry was positively correlated with mutations in the EGFR gene. Even further, the researchers determined that Native American ancestry was predominantly associated with oncogenic mutations in the EGFR gene, but not with non-oncogenic mutations.

Patients were then stratified by their self-reported smoking status and evaluated to determine the association between global ancestry and mutations in target genes. In both individuals who were never smokers and smokers, global Native American ancestry was found to be associated with mutations in the EGFR gene, indicating that the genomic differences associated with Native American ancestry are independent of smoking status.

Smoking increases the risk for KRAS-mutant lung cancers, while patients with lung cancer who are non-smokers more often develop EGFR-mutant lung cancer, Meyerson explained. However, we show in our study that EGFR-mutant lung cancer is also elevated among smokers with Native American ancestry.

Lastly, the investigators developed a local Native American ancestry risk score to assess the association of ancestry with EGFR mutation frequency across multiple distinct sites in the genome. In doing so, it was revealed that the correlation between ancestry and increased mutation frequency in the EGFR gene was stronger at the local genome level than the global genome level.

These results suggest that germline genetics in addition to environmental factors or socioeconomic status may have an influence on the risk of EGFR-mutant lung cancer among those with Native American ancestry, said Meyerson.

Many lung cancers are now treatable with targeted therapy or immunotherapy, Meyerson added. It is very important for patients with lung cancer to undergo somatic genetic testing to determine which treatments are most likely to be effective for their particular cancer.

Moving forward, the researchers suggested that future studies will still be necessary to comprehensively characterize lung cancer genomes from Latin American patients.

References:

1. Carrot-Zhang J, Soca-Chafre G, Patterson N, et al. Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations. Cancer Discovery. doi: 10.1158/2159-8290.CD-20-1165

2. Native American Ancestry Associated With Increased Mutations in EGFR Gene Among Latin American Patients With Lung Cancer [news release]. Philadelphia. Published December 2, 2020. Accessed December 4, 2020.

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Latin American Patients with Lung Cancer and Native American Ancestry See Increased EGFR Mutations - Cancer Network

Genetics

Insights on the Animal Genetics Global Market to 2027 – Strategic Recommendations for New Entrants – GlobeNewswire

Dublin, Dec. 22, 2020 (GLOBE NEWSWIRE) -- The "Animal Genetics - Global Market Outlook (2019-2027)" report has been added to ResearchAndMarkets.com's offering.

According to this report, the Global Animal Genetics market accounted for $4.48 billion in 2019 and is expected to reach $8.60 billion by 2027 growing at a CAGR of 8.5% during the forecast period. Some of the key factors propelling the growth of the market are growing preference for animal protein, increasing population, and increasing adoption of advanced genetic technologies. However, the shortage of skilled veterinary research professionals is the restraining factor for the growth of the market.

Animal genetics is the study of heredity in animals. It includes the study of colour, genetics, gene expression, and animal breeding for a wide variety of applications and is primarily focused on the passing of traits from one generation to the next.

By live animal, the porcine segment is expected to grow at a significant market share during the forecast period owing to the large consumer base for pork meat, as well as growing penetration of advanced genetic research. Based on geography, North America is anticipated to hold considerable market share during the forecast period which is attributed to the research activities being carried out on animal genetics and the adoption of strategic activities by industry players.

Some of the key players in Animal Genetics Market include Animal Genetics Inc, Cogent, Crv Holding B.V., Alta Genetics Inc, Genus PLC, Neogen Corporation, Inguran LLC, Groupe Grimaud La Corbiere SA, Hendrix Genetics BV, Topigs Norsvin, Vetgen, Ew Group GmbH, Zoetis Inc, Envigo Inc, and Urus.

Live Animals Covered:

Services Covered:

Genetic Materials Covered:

End Users Covered:

What the Report offers:

Key Topics Covered:

1 Executive Summary

2 Preface2.1 Abstract 2.2 Stake Holders 2.3 Research Scope 2.4 Research Methodology 2.4.1 Data Mining 2.4.2 Data Analysis 2.4.3 Data Validation 2.4.4 Research Approach 2.5 Research Sources 2.5.1 Primary Research Sources 2.5.2 Secondary Research Sources 2.5.3 Assumptions

3 Market Trend Analysis 3.1 Introduction 3.2 Drivers 3.3 Restraints 3.4 Opportunities 3.5 Threats 3.6 End User Analysis 3.7 Emerging Markets 3.8 Impact of Covid-19

4 Porters Five Force Analysis 4.1 Bargaining power of suppliers 4.2 Bargaining power of buyers 4.3 Threat of substitutes 4.4 Threat of new entrants 4.5 Competitive rivalry

5 Global Animal Genetics Market, By Live Animal 5.1 Introduction 5.2 Canine 5.3 Avian 5.4 Piscine 5.5 Poultry 5.6 Bovine 5.7 Porcine 5.8 Other Live Animals 5.8.1 Goat 5.8.2 Horse 5.8.3 Sheep

6 Global Animal Genetics Market, By Service 6.1 Introduction 6.2 DNA Typing 6.3 Genetic Disease Tests 6.4 Genetic Trait Tests 6.5 DNA Testing 6.6 Other Services 6.6.1 Forensic Testing 6.6.2 Prenatal Testing 6.6.3 Predictive and Presymptomatic Testing 6.6.4 Diagnostic Testing

7 Global Animal Genetics Market, By Genetic Material 7.1 Introduction 7.2 Embryos 7.2.1 Equine Embryos 7.2.2 Bovine Embryos 7.2.3 Other Animal Embryos 7.2.3.1 Porcine Embryos 7.2.3.2 Sheep Embryos 7.2.3.3 Goat Embryos 7.3 Semen 7.3.1 Canine Semen 7.3.2 Porcine Semen 7.3.3 Bovine Semen 7.3.4 Equine Semen 7.3.5 Other Animal Semen 7.3.5.1 Goat Semen 7.3.5.2 Sheep Semen

8 Global Animal Genetics Market, By End User 8.1 Introduction 8.2 Veterinary Hospitals & Clinics 8.3 Research Centers and Institutes 8.4 Diagnostic Centres

9 Global Animal Genetics Market, By Geography 9.1 Introduction 9.2 North America 9.2.1 US 9.2.2 Canada 9.2.3 Mexico 9.3 Europe 9.3.1 Germany 9.3.2 UK 9.3.3 Italy 9.3.4 France 9.3.5 Spain 9.3.6 Rest of Europe 9.4 Asia Pacific 9.4.1 Japan 9.4.2 China 9.4.3 India 9.4.4 Australia 9.4.5 New Zealand 9.4.6 South Korea 9.4.7 Rest of Asia Pacific 9.5 South America 9.5.1 Argentina 9.5.2 Brazil 9.5.3 Chile 9.5.4 Rest of South America 9.6 Middle East & Africa 9.6.1 Saudi Arabia 9.6.2 UAE 9.6.3 Qatar 9.6.4 South Africa 9.6.5 Rest of Middle East & Africa

10 Key Developments10.1 Agreements, Partnerships, Collaborations and Joint Ventures 10.2 Acquisitions & Mergers 10.3 New Product Launch 10.4 Expansions 10.5 Other Key Strategies

11 Company Profiling11.1 Animal Genetics Inc 11.2 Cogent 11.3 Crv Holding B.V. 11.4 Alta Genetics Inc 11.5 Genus PLC 11.6 Neogen Corporation 11.7 Inguran LLC 11.8 Groupe Grimaud La Corbiere SA 11.9 Hendrix Genetics BV 11.10 Topigs Norsvin 11.11 Vetgen 11.12 Ew Group GmbH 11.13 Zoetis Inc 11.14 Envigo Inc 11.15 Urus

For more information about this report visit https://www.researchandmarkets.com/r/z41eun

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Insights on the Animal Genetics Global Market to 2027 - Strategic Recommendations for New Entrants - GlobeNewswire

Genetics

Do Insiders Own Lots Of Shares In Fulgent Genetics, Inc. (NASDAQ:FLGT)? – Simply Wall St

Every investor in Fulgent Genetics, Inc. (NASDAQ:FLGT) should be aware of the most powerful shareholder groups. Insiders often own a large chunk of younger, smaller, companies while huge companies tend to have institutions as shareholders. I generally like to see some degree of insider ownership, even if only a little. As Nassim Nicholas Taleb said, 'Dont tell me what you think, tell me what you have in your portfolio.

With a market capitalization of US$1.1b, Fulgent Genetics is a decent size, so it is probably on the radar of institutional investors. Taking a look at our data on the ownership groups (below), it seems that institutions own shares in the company. Let's take a closer look to see what the different types of shareholders can tell us about Fulgent Genetics.

Check out our latest analysis for Fulgent Genetics

Many institutions measure their performance against an index that approximates the local market. So they usually pay more attention to companies that are included in major indices.

Fulgent Genetics already has institutions on the share registry. Indeed, they own a respectable stake in the company. This suggests some credibility amongst professional investors. But we can't rely on that fact alone since institutions make bad investments sometimes, just like everyone does. It is not uncommon to see a big share price drop if two large institutional investors try to sell out of a stock at the same time. So it is worth checking the past earnings trajectory of Fulgent Genetics, (below). Of course, keep in mind that there are other factors to consider, too.

We note that hedge funds don't have a meaningful investment in Fulgent Genetics. The company's CEO Ming Hsieh is the largest shareholder with 33% of shares outstanding. Han Gao is the second largest shareholder owning 7.3% of common stock, and BlackRock, Inc. holds about 6.5% of the company stock. Interestingly, the second-largest shareholder, Han Gao is also Chief Scientific Officer, again, pointing towards strong insider ownership amongst the company's top shareholders.

Our research also brought to light the fact that roughly 51% of the company is controlled by the top 4 shareholders suggesting that these owners wield significant influence on the business.

Researching institutional ownership is a good way to gauge and filter a stock's expected performance. The same can be achieved by studying analyst sentiments. Quite a few analysts cover the stock, so you could look into forecast growth quite easily.

The definition of company insiders can be subjective and does vary between jurisdictions. Our data reflects individual insiders, capturing board members at the very least. Management ultimately answers to the board. However, it is not uncommon for managers to be executive board members, especially if they are a founder or the CEO.

I generally consider insider ownership to be a good thing. However, on some occasions it makes it more difficult for other shareholders to hold the board accountable for decisions.

Our most recent data indicates that insiders own a reasonable proportion of Fulgent Genetics, Inc.. It has a market capitalization of just US$1.1b, and insiders have US$451m worth of shares in their own names. That's quite significant. It is good to see this level of investment. You can check here to see if those insiders have been buying recently.

The general public, with a 20% stake in the company, will not easily be ignored. While this group can't necessarily call the shots, it can certainly have a real influence on how the company is run.

We can see that public companies hold 4.4% of the Fulgent Genetics shares on issue. This may be a strategic interest and the two companies may have related business interests. It could be that they have de-merged. This holding is probably worth investigating further.

While it is well worth considering the different groups that own a company, there are other factors that are even more important. To that end, you should learn about the 5 warning signs we've spotted with Fulgent Genetics (including 2 which is are potentially serious) .

But ultimately it is the future, not the past, that will determine how well the owners of this business will do. Therefore we think it advisable to take a look at this free report showing whether analysts are predicting a brighter future.

NB: Figures in this article are calculated using data from the last twelve months, which refer to the 12-month period ending on the last date of the month the financial statement is dated. This may not be consistent with full year annual report figures.

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This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. *Interactive Brokers Rated Lowest Cost Broker by StockBrokers.com Annual Online Review 2020

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com.

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Do Insiders Own Lots Of Shares In Fulgent Genetics, Inc. (NASDAQ:FLGT)? - Simply Wall St

Genetics

Correlation and Causation: What Can Genetics and Genomics Tell Us about COVID-19? – BioNews

21 December 2020

Session three of the Progress Educational Trust (PET) annual conference explored the genetic and genomic links to susceptibility to severe COVID-19. Sarah Norcross, director at PET, opened the session with the unfortunate news that one of the speakers Dr Kri Stefnsson was unable to participate in the session due to illness.

The session was chaired by Dr Roger Highfield, science director at the Science Museum Group mild-mannered and a clear speaker, he chaired the session with ease. Dr Highfield introduced the first speaker Dr Sharon Moalem a scientist and physician who specialises in genetics. Dr Moalem is a bestselling author, with titles including: 'How Sex Works', 'Inheritance: How Our Genes Change Our Lives and Our Lives Change Our Genes', and 'The Better Half: On the Genetic Superiority of Women' (see BioNews 1050).

Dr Moalem focused his talk on the law of homogameity, and whether COVID-19 illustrates the genetic/genomic resiliency of women. He began by briefing the audience on the basics of mammalian genetics, how we have 46 chromosomes, one pair of which is sex chromosomes, containing either XX for a female, termed homogametic, or XY for a male, termed heterogametic. A system has arisen in females, where in each cell one X chromosomes is 'turned off', called X-inactivation or silencing. However, it has now been discovered that X-inactivation is not complete, and that about 25 percent of the second X chromosome is still active. Dr Moalem explained that this allows females to have more 'genetic horse power' within each of her cells.

X-linked conditions, such as fragile X, red-green colour blindness and Duchene muscular dystrophy, are more common in males, as men do not have another X chromosome. Females do not simply have a 'back up X', but in some cases their non-faulty gene produces and shares the required protein, essentially rescuing the cells containing the faulty gene, which would have died. In other cases, cells with such a mutation do not survive, but cell lines with the healthy X proliferate to compensate. This leads to tissues with an uneven distribution of active Xs, called X-skewing.

Moving onto COVID-19, why is the mortality rate for males higher than that for females? Dr Moalem proposed the law of homogameity, which predicts that the homogametic sex has a survival advantage across the life course. Females have a greater genetic diversity due to having an extra X-chromosome, which equates to 1000 more genes. The X chromosome contains many immune-related genes eg, TLR7 which is used by certain cells in the body to detect for single-stranded RNA viruses, like SARS-CoV-2, the virus which leads to COVID-19. As females have two variations of TLR7 they have two different immune cell populations to help detect the virus. However, there is a cost to homogameity increased autoimmunity, with 'long COVID' proving to be four times more common in women.

In the USA there is currently no requirement for drug approval from the FDA to use both male and female cells. Scientists can use just one sex, yet females' cells work in a corporative way. Dr Moalem believes there should be a completely separate drug approval process as many drugs behave differently in men and women.

Dr Highfield returned to introduce the second speaker Dr Qian Zhang a research associate at the St Giles Laboratory of Human Genetics of Infectious Diseases, at Rockefeller University in New York City. Dr Zhang's research specialises in inborn errors of immunity (IEIs) inherited disorders that impair normal immune development and function.

Dr Zhang focused her talk on type I interferon immunity in patients with life-threatening COVID-19 and began by explaining how early on in the pandemic it became clear that people infected with SARS-CoV-2 responded differently. Most were asymptomatic and developed either no or very mild clinical symptoms. A small proportion of patients developed life-threatening disease. This phenomenon is seen in all infectious diseases from bacteria, fungi and viruses.

Dr Zhang and her research team studied whether the same genetic mutations already known to be associated with life-threatening influenza infections also increase the risk of life-threatening COVID-19 pneumonia. There are three genes, TLR3, IRF7 and IRF9, in the type I interferon pathway that are mutated in people who develop life-threatening influenza. In addition, ten further genes, IFNAR1, IFNAR2, STAT1, STAT2, IRF3, UNC93B, TRIF, NEMO, TRAF3 and TBK1, are reported to affect severity of other viral infections.

Type I interferon is a cytokine and has 17 different subtypes, which lead to the stimulation of several hundred interferon-stimulated genes that have an antiviral function. Hence, if this pathway is disrupted by a genetic mutation, viruses are able to gain a foothold more easily.

Dr Zhang's team sequenced the whole of the genome of over 600 severe COVID-19 patients to determine whether they had mutations in any of these 13 genes and discovered over 118 variants, of which, 24 resulted in loss of function.

Four patients with autosomal recessive mutations causing a complete loss of function in IRF7 and IFNAR1had never been hospitalised before contracting COVID-19, much to Dr Zhang's surprise. IRF7 is a transcription factor that amplifies the antiviral signal of type I interferon, and IFNAR1 is one of two proteins that make the receptor for type I interferons. Patients with these mutations are unable to mount an interferon response to COVID-19 infection.

Dr Zhang reassuringly explained that these mutations are rare, less than one in 1000 in the population, as such they cannot explain why there are so many people dying of COVID-19. This led Dr Zhang to the second part of her research: studying whether auto-antibodies against type I interferons lead to the same phenotype as these rare mutations.

Over ten percent of patients with life-threatening COVID-19 make auto-antibodies against two of the type I interferons. These neutralising auto-antibodies can entirely block the protective effect of type I interferons, which may be the cause of severe COVID-19.

Surprisingly, 95 percent of patients with these auto-antibodies were male and only six were female. One of these female patients had incontinentia pigmenti (IP), which is caused by a NEMO mutation on the X chromosome, leading to skewed X-inactivation a perfect example of the genetic diseases Dr Moalem was discussing earlier in the session. Even though such patients have two X chromosomes, most of the tissues in their bodies express just one X chromosome, and so these females are more similar to males in terms of susceptibility.

Combining both parts of her research, Dr Zhang's team discovered that selected patients with TLR3 and IRF7 mutations could simply be treated with type I interferon. However, this treatment did not work for patients with IFNAR1 mutations because the receptor is absent, but treatment with wildtype IFNAR1 was successful. Unfortunately, neither treatment worked for patients with auto-antibodies.

In her opinion COVID-19 could be considered an X-linked disease, even though the candidate on the X-chromosome has yet to be discovered and furthermore, type I interferon immunity is essential to control COVID-19 infection.

Dr Highfield returned to update the audience on Dr Stefnsson's research, investigating the genetic code of each COVID-19 infection in Iceland, giving an insight into the origins, and how the infection was caught, spread and mutated. Surprisingly, a large number of cases came from the UK. Similar research in the UK has detected 1356 independent introductions of the virus, mostly due to inbound international travel a third came from Spain, over a quarter from France and 14 percent from Italy.

The session provoked interesting discussions within the Q&As, with the first asking Dr Moalem whether females are less severely affected by other viruses, which he concluded as true, particularly for influenza. But even for HIV-1, women are much better at clearing the virus and have a much lower viral load.

With a personal interest, I took the opportunity to ask Dr Zhang whether patients with type I interferon IEIs were more susceptible to severe COVID-19, as such a disease affects members of my own family. Dr Zhang confirmed that such patients are more likely to suffer with severe COVID-19 and had now tested 20 IP patients discovering at least a quarter had high levels of autoantibodies to type I interferons. She warned that these females should be very cautious and shield as much as possible, as any patient with auto-antibodies is very difficult to treat. Reassuringly, patients with certain genetic mutations that do not have high levels of autoantibodies to type I interferon can simply be treated early with interferon injections.

I will leave with a final comment from Dr Moalem: 'Men are more biologically fragile when compared to women.' Whoever said that women were the weaker sex?

PET would like to thank the sponsor of this session, the Anne McLaren Memorial Trust Fund, and the other sponsors of its conference - the Edwards and Steptoe Research Trust Fund, ESHRE, Wellcome, the European Sperm Bank, Ferring Pharmaceuticals, the London Women's Clinic, Merck, Theramex, Vitrolife and the Institute of Medical Ethics.

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Correlation and Causation: What Can Genetics and Genomics Tell Us about COVID-19? - BioNews

Genetics

Bryan Sykes obituary – The Guardian

The human geneticist Bryan Sykes, who has died aged 73, pushed forward the analysis of inherited conditions such as brittle bone disease and double-jointedness, and was one of the first to extract DNA from ancient bone.

The same Bryan Sykes, holder of a personal chair at Oxford University, analysed hair supposedly taken from mythical hominids such as the Bigfoot and Yeti, and announced the results in a three-part television series. His delight in science and enthusiasm for communicating it to popular audiences were both aspects of an expansive personality that alternately inspired and exasperated his colleagues.

Sykes was not the only one to realise that the ability to read sequences of DNA code opened up the possibility of tracing human ancestry to our early origins. He was exceptional, however, in seeing that the wider public would connect emotionally to these stories if the dry details of the science could be presented accessibly. His book The Seven Daughters of Eve (2001) proposed that every living European could trace his or her ancestry to one of seven women living between 8,500 and 45,000 years ago. They, in turn, would share descent from a single Eve, who lived in Africa even earlier. He gave the seven women names and, anticipating peoples desire to know which tribe they belonged to, the same year set up the first direct-to-consumer genetic testing company, Oxford Ancestors, as an Oxford University spinout.

Sykes began this work long before modern methods of whole-genome DNA sequencing were available. When, in the late 1980s, he, Erica Hagelberg and Robert Hedges of Oxfords Research Laboratory for Archaeology first extracted DNA from bones up to 12,000 years old, they opted to focus on mitochondrial DNA (mtDNA). There are more than 1,000 mitochondria in each cell but only one nucleus (where most of our DNA resides), increasing the chances of retrieving mtDNA. But Sykes soon appreciated that it has another property. It is inherited largely unchanged in the maternal line over thousands of years, while nuclear DNA is mixed with every generation. To test whether it would be possible to use mtDNA to trace distant ancestors, Sykes first confirmed that domesticated golden hamsters from numerous locations, which he had heard were all descended from a single wild-caught female, had the same signature in their mtDNA.

Sykes went on to use this method to solve the mystery of the origins of islanders scattered throughout the Pacific Ocean: whether they had arrived from the Americas, as Thor Heyerdahl had suggested on the basis of the 1947 voyage of the Kon-Tiki raft, or from Asia. Receiving hospital treatment on Raratonga in the Cook Islands after a motorcycle accident while on holiday in the mid-90s, Sykes realised he could resolve this uncertainty using mtDNA. He went on to collect samples from Pacific islands and Pacific Rim countries, and established that Polynesia was in fact entirely settled from Asia.

In 1987 he won a British Association for the Advancement of Science media fellowship that enabled him to spend seven weeks working with Channel 4 News. The lessons he learned about what makes a good story came to the fore in Seven Daughters and his subsequent books.

Adams Curse (2003) drew some controversial conclusions about the influence of the Y chromosome on male behaviour, but also covered studies that traced descent via Y chromosomes. These pass from father to son, like British surnames, though without the uncertainty introduced by nonpaternity events. When the chairman of the pharmaceutical company GlaxoSmithKline, Sir Richard Sykes, wondered if the two of them might be related, Bryan collected DNA from dozens of Sykeses in Britain. He discovered that more than half of them shared the same unusual Y chromosome variant, suggesting a single founding father in Yorkshire in the 13th or 14th century.

His collaboration with enthusiasts searching for the Bigfoot and Yeti raised eyebrows even higher. Hairs from bits of mystery creatures that had long lain in museums and temples made their way to his lab. The three-part Channel 4 series Bigfoot Files (2015) maintained the suspense to the end, but all the samples proved to come from known animal species. A hasty claim that a Yeti specimen was a match to a prehistoric polar bear proved to be a case of mistaken identity. For Sykes it was all education as entertainment he never seriously believed that such creatures existed, but sought to encourage curiosity rather than squashing it.

Born in London, Bryan was the son of Frank Sykes, an accountant, and his wife, Irene. He attended the independent boys school Eltham college, near his home in south-east London, and developed passions for the natural world, experiments and inventions. He also excelled at cross-country running, rugby and swimming.

He studied biochemistry at the University of Liverpool, and did a PhD at the University of Bristol on the connective tissue protein elastin. He arrived at Oxford in 1973 as a research fellow in the Nuffield department of orthopaedic surgery, continuing to work on elastin and collagen. By the time he was appointed lecturer in molecular pathology in 1987, he was deploying new genetic techniques to explore inherited disorders of bone and connective tissue. His collagen genetics group moved from orthopaedic surgery to Oxfords newly established Institute of Molecular Medicine, founded by the geneticist Sir David Weatherall, who was an important mentor. He was appointed to a personal chair in human genetics in 1997, and formally retired in 2016.

Sykess expertise in bone led to his involvement in the effort to extract DNA from ancient specimens. As his interest in studies of human populations developed, he recruited lab members who worked in that area alongside those who continued his pathological studies. Colleagues remember the lab as being unusually collaborative, though occasionally disrupted by TV cameras, and Sykes himself as encouraging and supportive. He took them all to Scotland in 1998 to assist with the collection of samples for his work on prehistoric migration into Britain (published as Blood of the Isles, 2006). A keen fisherman, he got out his rods in the bar of their hotel to teach them how to cast a fly.

Sykes was extremely smart and a brilliant communicator, with a streak of mischief: he didnt turn a hair when Italian colleagues casually invited him to access the bone store at Pompeii by climbing over a fence (they had arrived before opening time), and there was always champagne in the lab when anyone published a paper.

Sykes met Sue Foden when she was a student in Oxford, and they were married in 1978. Though the marriage was annulled in 1984, he and Sue remained close and had a son, Richard, born in 1991. His later marriage to Janis Wilson ended in divorce. In 2007 he collaborated with the Danish artist Ulla Plougmand on an exhibition featuring the seven daughters of Eve, and their subsequent relationship lasted until the end of his life. In later years, as his health deteriorated, Bryan was increasingly supported and cared for by Sue. She, Ulla and Richard survive him.

Bryan Clifford Sykes, geneticist, born 9 September 1947; died 10 December 2020

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Bryan Sykes obituary - The Guardian

Genetics

British scientists find worrying changes in the coronavirus – Los Angeles Times

In the United Kingdom and several other countries, a disconcerting cluster of genetic changes has been detected in the coronavirus that causes COVID-19, prompting British Prime Minister Boris Johnson to all but cancel Christmas in Britain.

At least 1,619 samples of the virus collected from infected Britons contained a distinctive set of 17 genetic alterations, including three that appear to make the virus easier to transmit from person to person and improve its ability to sneak past the immune systems defenses.

The changes in the coronaviruss RNA were detailed in a report by British researchers who use time-stamped genetic sequences of the virus to track the pandemics progress. The COVID-19 Genomics UK Consortium said the unexpectedly large number of changes, and their potential influence on key parts of the virus, require urgent laboratory characterisation and enhanced genomic surveillance worldwide.

The same collection of RNA alterations has been detected in viral samples culled from four other countries, the British geneticists added.

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Several of the changes appear to alter the virus spike protein, which the coronavirus uses to pick the lock to human cells and convert them into factories for its own production. Two of the changes appear to make cells in the respiratory tract and elsewhere more vulnerable to invasion, and they increased the virus infectivity and its virulence in mice.

While both mutations have been seen separately, theyve only been seen together in the new clutch of cases, the British researchers said.

Thats a potential problem because all five of the COVID-19 vaccines furthest along in development train the immune system to target the spike protein. In theory, these genetic changes might alter the protein enough to erode the effectiveness of vaccines made by Pfizer and Moderna both of which are being rolled out in the U.S. as well as three others close behind them.

In a report last week, the British researchers wrote that there is currently no evidence that this variant (or any other studied to date) has any impact on disease severity, or that it will render vaccines less effective, although both questions require further studies performed at pace.

Over the weekend, a panel of vaccine experts pressed the U.S. Centers for Disease Control and Prevention on whether the British strain would alter the effectiveness of the Moderna vaccine that received emergency use authorization from the Food and Drug Administration on Friday. Officials assured committee members that Moderna and other vaccine makers will perform deep sequencing on these so-called breakthrough cases to detect whether such changes have occurred.

The developments caused Johnson to renew lockdown measures across much of England, including travel restrictions and the shuttering of pubs, gyms, theaters and hair salons. He said the moves were taken in response to findings that the RNA changes could make the virus up to 70% more transmissible.

This is spreading very fast, the prime minister said.

By Sunday, France, Germany, Italy, the Netherlands, Belgium, Austria, Ireland and Bulgaria all said they would ban incoming flights from the U.K.

Samples of the SARS-CoV-2 virus that include some or all of 17 changes were first detected in samples from two Britons on Sept. 20. One was collected from a person in Kent in southeastern England, and the other came from a person in the London metropolitan area the next day.

By Friday, viral samples with roughly the same genetic fingerprint represented 6% of all viral samples sequenced in the United Kingdom since Nov. 1. (Researchers at the U.K. genetics consortium sequence roughly 10% of viral samples from all Britons who test positive for coronavirus infections.)

Emma Hodcroft, a geneticist working with a viral tracking group called Nextstrain, said the family of changes has also been detected in samples in Denmark and Australia, which were probably imported from Britain. Belgium and Italy are also following up on reports that the mutation has been detected within their borders.

Researchers in South Africa also have detected infections that bear some of the same changes, including ones in the virus spike protein.

Those who have followed the virus genetic journey during the pandemic were quick to note that not all alterations should set off alarm bells. As with any family tree, the virus spins off distinct lineages as it spreads across time and space, and each one is thought to pick up one or two changes a month.

As a result, the coronavirus has incorporated thousands of modifications since it emerged late last year.

While such incremental changes can gradually shift a virus behavior over time, none has yet been seen to suddenly make this coronavirus more dangerous to those it infects or to boost its ability to jump from person to person.

But this case may be different, the British researchers warned.

The abrupt appearance of so many samples with so many of the same potentially significant changes is, to date, unprecedented in the global virus genomic data for the COVID-19 pandemic, they wrote.

While scientists have been aware of some of these genetic variants since September, theyve circulated far more widely in recent weeks. The researchers hypothesized that the cluster of changes may have been prompted by the virus efforts to overcome the suppressive effects of antiviral drugs or antibody-rich blood plasma donated by people who have recovered from COVID-19.

The researchers noted that alterations tend to accumulate very quickly in people who take months to clear a viral infection, as well as in people with weakened immune systems. As their infections linger, those people become incubators for multiple versions of the virus that sicken them simultaneously, allowing them to swap and share their genetic variants.

Other scientists who have tracked the pandemics twists and turns said its not entirely clear that the genetic changes either singly or collectively have made the virus more transmissible.

The early assessments of transmissibility appear to be inferred in part from the growth of samples collected around Kent and London. But Dr. Marc Suchard, a UCLA biomathematician, cautioned that population density, different rates of mask-wearing and social distancing, and other factors can influence how fast a particular virus spreads.

One might say the evidence is suggestive of increased transmissibility, Suchard said. But nailing that down will require a careful scrubbing of epidemiological data and laboratory testing, he said.

Along the way, he added, scientists may discover that as the virus becomes better at spreading, it could also become less dangerous a tradeoff that has taken the bite out of other epidemics.

Dr. Arturo Casadevall, a Johns Hopkins University microbiologist, said that if the genetic changes will have any effect on COVID-19 vaccines, it will be minimal.

I am not alarmist about this, Casadevall said.

Even changes that significantly alter the virus spike protein dont affect plenty of other targets, called epitopes, that antibodies use to recognize and kill virus, he said.

So for the virus to completely defeat vaccine, it would have to change in many, many places where the virus binds to cells, he said. And that is a very low probability event.

That view is shared by Trevor Bedford, a geneticist at the Fred Hutchinson Cancer Research Center who has tracked the coronavirus genetic meanderings.

Im not concerned that these variants will significantly reduce vaccine efficacy in the 2021 rollout, Bedford said in a Twitter thread. The strong immune response to the mRNA vaccines would suggest that a large antigenic change would be needed to significantly reduce efficacy.

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British scientists find worrying changes in the coronavirus - Los Angeles Times

Genetics

Canadian company Inagene Diagnostics launches the other test you need to take to protect your health in case of COVID – GlobeNewswire

TORONTO, Dec. 17, 2020 (GLOBE NEWSWIRE) -- As we head into the winter months, Canadians are doing everything they can protect themselves from the risk of getting sick. It turns out that if you DO find yourself in hospital, you may face a different set of risks the risk of receiving the wrong medication based on your genetics. Now, a new test can help.

Genetic variations that affect how individuals respond to medications are not uncommon, according to Dr. Kathy Siminovitch Chief Scientific Advisor to Inagene Diagnostics; More than 98% of us unknowingly carries gene variants that will cause us to have an unexpected reaction to one or more commonly used drugs, either a lack of, or reduced clinical effect, or worse - unexpected, potentially serious side effects. Finding the best treatments and doses for every individual is a challenging process that can be greatly facilitated by incorporating genetic information so as to achieve the best possible outcome.

Now a new innovation called pharmacogenetic testing promises to significantly reduce the time and risk involved in finding the right drug and dose through medication trial and error. Inagene has introduced a simple cheek swab test that helps doctors predict how individuals will respond to commonly used drugs before they are administered. The test is ordered online and done at home, with results ready to share with prescribers within 7 days.

A recent study confirmed that 90% of patients hospitalized with COVID-19 end up receiving at least one medication that is affected by pharmacogenetics, and almost a quarter receive four or more. Because very ill patients cannot afford treatment failure or adverse effects, quickly finding the most effective and safe treatments and doses is critical. The authors concluded that having pharmacogenetic test results to guide treatment would have provided the opportunity to improve clinical care for nearly all individuals hospitalized with COVID19 by helping to guide clinicians to the most optimal drugs and doses, while avoiding the rest.

Inagene Diagnostics Inc. is a CLIA accredited Canadian pharmacogenetic testing company located in Toronto. Inagenes Personalized Insights tests focus on providing comprehensive and reliable genetic tests to guide drug section and treatment. Learn more at inagene.com.

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For all inquiries contact:

Nancy White

CEO Inagene Diagnostics Inc.

customerservice@inagene.com

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Canadian company Inagene Diagnostics launches the other test you need to take to protect your health in case of COVID - GlobeNewswire