Category Archives: Human Genetics

The advent of technology making feasible elucidation of whole genomic sequencing over the past 30 years has led to reports of many if not most important or interesting animal genomes (including the most celebrated results of the Human Genome Project) (see, e.g., "Nautilus pompilius Genome Determined"; "Giraffe Genome Reveals Relevant Adaptations"; "Avocado Genome Elucidated; Durum Wheat Genome Revealed"; "Rose Genome Reveals Its Exquisite Complexities"; "Silver Birch Genetics Explained"; "Genomic Sequence of Strawberry Determined"; "Koala Genome Sequenced"; "Tomato Genome Determined"; "Lowland Gorilla Genome Sequenced"), as well as important historical relationships newly appreciated (see, e.g., "Did Neanderthal DNA Persist in Modern Humans as a Defense against Xenobiotic Viruses?"; "Chicken Origins Established (But Philosophical Questions Remain)"; "Genetic Analyses of Sweet Potato Genome Sheds Light on Speciation and Global Dispersion Patterns"; "The Domestication History of Apples Revealed by Genomic Analysis"; "Evidence of Geographic Change in Central America from Genome Studies of Eciton Ant Species"; "Dolphin Genes Show Relationships between Large Brains and Energy Metabolism Similar to Humans and Elephants").

But what has become evident recently is that most of these genomes were in one way or another incomplete, due typically because there were regions of this or that genome that were resistant to accurate sequencing or come other biologic idiosyncrasy. The most recent example of this reminder of the complexity of biological organisms is our old friend the domestic cat, which built (as most of the new studies do) on the earlier genomic elucidations. In this case, the earlier study in question was published in 2014, when an international effort led by Stephen J. O'Brien at the Oceanographic Center, Nova Southeastern University, Ft. Lauderdale, Florida reported the complete genomic sequencing of the domestic cat, Felix catus. The report, entitled "Annotated features of domestic cat Felis catus genome," was published in GigaScience 2014, 3:13 (August 5, 2014) (see "Domestic Cat Genome Sequenced"). The study reported sequencing of a female Abyssinian cat named Cinnamon, a mixed-breed cat from Russian named Boris, and Sylvester, a wildcat ancestor of domestic cats. The report showed that domestic cats have retained "a highly conserved ancestral mammal genome organization" in comparison with ancestral cats (see Driscoll et al., 2007, "The near eastern origin of cat domestication," Science 317: 51923). Both species, F. catus and Felix silvestris, have 38 chromosomes, 18 pairs of autosomes, and two pairs of dimorphic gender-determining chromosomes. Details of the domestic cat genome structure included the presence of 217 loci of endogenous retrovirus-like elements (amounting to 55.7% of the entire genome, comprised of long interspersed elements (LINEs), short interspersed elements (SINEs), satellite DNA, retroviral long terminal repeats (LTRs) and "others"); 21,865 protein coding genes (open reading frames or ORFs), detected by comparison with eight mammalian genomes (from human, chimpanzee, macaque, dog, cow, horse, rat, and mouse); and a wealth of genetic variability in single nucleotide polymorphisms (SNPs), insertion/deletion events (indels); novel families of complex tandem repeat elements; and short terminal repeat (STR) loci.

The report also contained an extensive comparison between domestic cats and other species ("reference genomes") in terms of gene numbers, using genes with the longest mRNA and corresponding coding sequences (click on table to expand).

More recently, further results of applications of improved genomic sequencing methods and technologies have provided a more comprehensive elucidation of the feline genome and insights into genetic bases for disease. A paper published in the Public Library of Science, entitled "A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism," PLoS Genetics 16(10): e1008926 on October 20, 2020, reported a revisit of the genomic sequence of Cinnamon, an Abyssinian breed domestic cat previously sequenced. Rather than focusing on one cat, this group* performed whole genome sequencing (WGC) of 54 domestic cats and aligned the sequences to detect single nucleotide variants (SNVs) and structural variants (SVs). The distribution and relatedness of the cats in this study is shown in this graphic:

Their aim was to identify the sequence comprising the ~300,000 gaps in the annotated sequence reported to the Cinnamon Abyssinian, to produce a new reference cat genome denoted in relevant databases as Felis_catus_9.0. This genome comprised 2.84 gigabasepairs (Gb), of which only 1.8% (1.38 megabasepairs, Mb) was not assigned to a specific chromosomal location. The sequencing and comparison identified 19,748 genes, 376 of which were novel (i.e., had not been identified in Cinnamon's DNA) and 178 genes found in the original annotations but not found here. (The authors note the presence of 54 diverse individual cats from which the genes were determined as a possible source of this disparity.) A greater extent of LINE/L1 repetitive elements were detected, which these researchers attributed to better assembly (i.e., the repetitiveness and gaps did not mask these elements in the latest assembly). The average number of SNVs detected per cat was 9.6 million (for comparison humans have ~5 million); inbred cats showed a lower number (~8 million) while outbred cats showed a higher number (> 10.5 million). Of these, researchers detected 128,844 synonymous SNVs in protein-coding sequences (i.e., where the two sequence encoded proteins having the same amino acid sequence), 77,662 missense SNVs (wherein the protein encoded differed in amino acid sequence, including truncated sequences and out-of-frame mutants), and 1,179 loss-of-function (LoF) SNVs. LoF and missense SNVs were associated with depletion in comparisons between orthologous cat and human DNA sequences, whereas synonymous SNVs were enriched by 19.2%. Statistical analyses found that in cats and humans there was selection against missense and LoF SNVs in genes under selective pressure (i.e., where the genetic changes resulted in phenotypes deleterious to individuals carrying them). These results further indicated that these classes of SNVs were not distributed randomly in the cat or human genome.

Turning to structural variants, these researchers detected an average of 44,900 SVs per cat (a frequency four-fold higher than in humans), comprising 134.3 Mb; of the structural variant types, deletions averaged 905 bp, duplications 7,497 bp, insertions 30 bp, and inversions 10,993 bp. In total they reported 208,135 SVs detected in 54 sequenced cat genomes, with 123,731 (60%) were deletions, approximately 39,955 insertions, 35,427 inversions, and 9,022 duplications were identified. The majority of these were common across cat breeds, indicating tolerance. 58.15% of these SVs were intergenic in location, 40.22% intronic, and only 1.06% found in exons, "potentially impacting 217 different protein coding genes. As the scientists noted:

Conversely, the proportion of some SV types found in certain gene regions varied from their genome-wide averages. For example, in regions 5 kb upstream and downstream of genes, duplications were increased approximately two-fold. For exonic regions, 74% of SVs were deletions, an increase from the genome wide level of 59.45%. For 5' untranslated regions (UTRs), the majority of SVs were inversions, which only represent 17.02% of total SVs. These results suggest an interaction between the impact of SV types and the potential function of the gene regions they are found in.

Sixteen of the identified variants were predicted to cause disease, based on comparisons with human genome sequences known to be sufficiently similar. These included one involving a tumor suppressor gene FBXW7 associated with feline mediastinal lymphoma, prevalent in Siamese cats and Oriental shorthaired cats. Other variants detected and their related diseases were in the FAM13B gene, resulting in ectodermal dysplasia (in a random-bred cat); the CYFIP2 gene associated with urate stones (Egyptian mau); and the SH3PXD2A gene, associated with feline infectious peritonitis (random bred cat).

The genetic roots of dwarfish more complicated according to these researchers, involving "a complex deletion coupled with a nearby potential duplication event" on cat chromosome B1, that disrupted the gene for UDP-glucose-6-dehydrogenase (UGDH). This trait is inherited as an autosomal dominant mutant and a breed-standard for Munchkins, characterized by shortened limbs and anormal torso. Here, the scientists report that:

SV analysis within the critical region previously identified by linkage and GWAS on chromosome B1:170,786,914175,975,857 revealed a 3.3 kb deletion at position chrB1:174,882,897174,886,198, overlapping the final exon of UDP-glucose 6-dehydrogenase (UGDH). Upon manual inspection of this SV, a 49 bp segment from exon 8 appeared to be duplicated and inserted 3.5 kb downstream, replacing the deleted sequence. This potentially duplicated segment was flanked by a 37 bp sequence at the 5`end and a 20 bp sequence at the 3' end, both of unknown origin.

(This topography is illustrated in the Figure below.) The scientists further hypothesized that the known activity of the affected gene, UGDH, which is involved in "proteoglycan synthesis in chondrocytes" could effect this phenotype by interfering with development. Evidence for this mechanism was observed in the epiphyseal plate, which in Munchkins showed "a disorganized columnar arrangement" and proteoglycan depletion. They report that sequencing the mRNA produced by the mutant UGDH is yet to be reported, which would perhaps shed light on whether the role of this mutation was as they propose it to be.

This group published a more recent paper in March 2021, entitled "Ultracontinuous Single Haplotype Genome Assemblies for the Domestic Cat (Felis catus) and Asian Leopard Cat (Prionailurus bengalensis)," in the Journal of Heredity, 112(2): 16573, providing additional details relating to its analysis of the domestic cat and leopard cat components of the hybrid genome.

The results reported in these papers illustrated how far we have come and perhaps how far we have to go in using genetic methods for identifying the causes and possible cures for a variety of diseases.

*Reuben M. Buckley, Brian W. Davis, Wesley A. Brashear, Fabiana H. G. Farias, Kei Kuroki, Tina Graves, LaDeana W. Hillier, Milinn Kremitzki, Gang Li, Rondo P. Middleton, Patrick Minx, Chad Tomlinson, Leslie A. Lyons, William J. Murphy, Wesley C. Warren

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Further and More Detailed Study of Domestic Cat Genome - JD Supra

NEW YORK Researchers from the UK and Switzerland are teasing out interconnections between gene expression, metabolites, and other genomic features in blood samples from hundreds of individuals over time to better understand the dynamic interactions behind aging and age-related disease.

"Multiomics data also has enormous utility in identifying the functional mechanisms underlying disease states, and linking genetic variants to their downstream effects on physiology," explained King's College London's Kerrin Small, a leader in genomics in the twin research and genetic epidemiology department, who shared the findings at the American Society of Human Genetics annual meeting on Thursday.

As part of the multiomic multiple tissue human expression resource, or MultiMuTHER, project, the researchers used RNA sequencing and metabolomics to track blood gene expression and metabolite profiles, respectively, in samples collected over time from 335 female TwinsUK participants. The participants came from both identical and non-identical twin pairs and ranged in age from roughly 30 to 85 years old at the time of their first sampling visit, Small said, noting that most of the individuals were in their 50s or 60s when the study began.

Over nine years, the team collected three or more samples from each participant, generating RNA-seq profiles for 16,292 genes that were analyzed in whole blood alongside Metabolon-based profiles for nearly 1,200 metabolites in matched blood serum samples.

From these longitudinal samples, the investigators found that the collection of expressed genes tended to remain steady within each individual. And while expression levels were sometimes dialed up or down with age across the participant population, the expression of specific genes sometimes bucked that trend within a subset of individuals, shifting in the opposite direction or remaining steady over time.

"We hope to use the other variables in the dataset to determine whether these individual trajectories are environmentally, clinically, or genetically driven," Small explained, noting that the analyses done so far have taken potentially confounding factors into account, such as participants' age at study onset, seasonality, and the cell type composition of blood samples.

Along with similar analyses on transcript splicing and metabolite profiles in the participants over time, the team went on to unearth more than 105,600 gene expression-metabolite associations, which involved more than 80 percent of the genes and 95 percent of the metabolites analyzed.

"Genes showing longitudinal change over time were found to have a higher number of gene-metabolite associations than those exhibiting stable expression," Small noted, "whereas metabolites exhibiting longitudinal variation did not show a difference in the number of associated genes."

Following up on such associations, the team took a closer look at everything from the nature of the most association-rich metabolites or environmental metabolites impacting gene expression to the stability of gene-metabolite associations over time and related genotypes.

As such analyses continue to progress, the researchers are also planning to layer on clinical phenotype data to try to tease out the potential consequences of the stable and variable associations they are uncovering.

"[W]e have performed one of the largest multiomic longitudinal studies of concurrently measured gene expression and metabolite levels in whole blood, identifying over 100,000 gene-metabolite associations," Small and her co-authors concluded in an abstract for the presentation, arguing that the study "provides novel insight into the interplay between gene expression and metabolites, and may inform systems-wide approaches to projection of temporal progression of age-related diseases."

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MultiMuTHER Team Tracks Expression, Metabolite Relationships in Aging TwinsUK Participants - GenomeWeb

By Dave Larsen

The National Institutes of Health awarded two University of Dayton geneticists a five-year, $1.65 million grant to study how genes regulate three-dimensional patterning and growth during early eye development to understand the genetic basis of childhood retinal diseases and birth defects in the human eye.

Department of Biology professors Amit Singh and Madhuri Kango-Singh are co-principal investigators on the grant, which started Aug. 1 and continues through June 2026. They will use the fruit fly eye model to study the genetic machinery involved in regulating how an eye is formed at the cellular level.

Singhs previous eye development research, funded under a $485,000 National Institutes of Health (NIH) grant awarded in 2017, focused on how genes regulate the process of transforming a single layer of cells into a three-dimensional organ.

That research will expand under the new grant with the addition of Kango-Singh, whose research focus is cancer biology, as co-principal investigator. She will focus on a genetic signaling pathway that regulates growth during eye development.

Not only do you need to make the structure, but it needs to grow to the right size and in the right way, so that you make what would be normal eyes on the heads of flies, said Kango-Singh, who was a co-investigator on the 2017 grant. The same genes function in the development of eyes in other animals and humans, so it could also be interesting to learn about how that process pans out and whether it is involved in birth defects.

Scientists use fruit flies to model human diseases at the cellular and molecular levels because they have similar genetic traits to those of humans. The flys entire life cycle is just 12 days, which allows researchers to study the transmission of hereditary traits and investigate the genetics of disease across at least 24 generations in a year.

Kango-Singh will spearhead the effort to understand how growth pathways regulate this basic process of forming an eye, while Singh will remain focused on the core genetic machinery of eye development.

Their goal is to gain better insights into eye formation, including birth defects associated with a particular transcription factor a protein involved in the controlling expression of other genes.

What we have proposed here is that this transcription factor is required for the placement of the eye on the head of an organism, Singh said. In laymans language, eyes are not the same for all organisms on the head they are placed far apart or close together. We have hypothesized that this transcription factor might be involved in that. It also regulates growth. So, thats the reason we have brought growth and patterning together, and this can be a new component in the eye development machinery.

Despite their separate research interests, the couple has collaborated on a number of projects and publications for more than 27 years. In May 2020, they published the second edition of their well-received book about the fruit fly, Molecular Genetics of Axial Patterning, Growth and Disease in Drosophila Eye.

Under the new NIH grant, Singh and Kango-Singh will each hire a postdoctoral researcher and two graduate assistants to work in their respective labs. In addition, Singh recruited six new undergraduate students for the project. Kango-Singh has six undergraduates working in her lab and hopes to hire three or four more to work on the project.

One of the pillars of UDs vision is experiential learning for undergraduate students, Singh said. We actively involve these students in our research. They are primary authors on peer-reviewed publications. They present at local, regional and international meetings.

He said exposing undergraduate students to cutting-edge research and instrumentation such as the Olympus confocal laser scanning microscope and Zeiss Apotome fluorescence microscope produces well-rounded scientists who are well-prepared for the job market or graduate school.

Kango-Singh, director of the Universitys biology graduate program, credits their NIH grant to the participation of graduate students in their research.

Having a vibrant graduate program at UD in biology is crucial for the success of all faculty with grants, she said. It is the lifeline for success with funding and publications the two things crucial for growing the reputation of the graduate program and the University.

Singh said 70% of their success with the NIH grant is due to the hard work of graduate students. These people are really working 24/7 to make these things happen, he said.

For more information, visit the Department of Biology website.

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National Institutes of Health awards $1.65 million to University of Dayton researchers to study genetic basis of childhood diseases and birth defects...

THOUSAND OAKS, Calif., Oct. 26, 2021 /PRNewswire/ --Amgen (NASDAQ: AMGN) today announced that it has been selected as one of the World's Best Workplaces for 2021 by Fortune magazine and Great Place to Work. Amgen ranked eighth among the 25 companies named to the list. Those on the list were selected from 10,000 companies, representing the voices of nearly 20 million employees in more than 100 countries.

"We are very proud of this honor," said Robert A. Bradway, Amgen's chairman and chief executive officer. "To be recognized on a global scale demonstrates our ongoing commitment to providing staff with an environment in which they are able to grow and thrive even during challenging times."

"The World's Best Workplaces are the most sweeping and consistent examples of inclusive company cultures we've ever known," said Michael C. Bush, chief executive officer of Great Place to Work. "In a global workforce, alignment is everything, and these companies are fortifying their culture around the world a nearly impossible feat. Even when tested by the pandemic, these companies recognize sub-communities in each region and their leaders carry an equitable employee experience across cultures."

Earlier this year, Amgen was ranked by Great Place to Work as the seventh best workplace in Europe. Additionally, 25 Amgen affiliates around the world have either been certified or recognized by Great Place to Work nationally. The Fortune World's Best Workplaces list is available at https://www.greatplacetowork.com/best-workplaces-international/world-s-best-workplaces/2021.

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

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

For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

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

SOURCE Amgen

http://www.amgen.com

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Fortune and Great Place to Work Name Amgen One of the World's Best Workplaces in 2021 - PRNewswire

This week 23andMe made Fast Company's first annual list of "Brands that Matter," an award honoring companies and nonprofits with a mission or ideals that have had a cultural impact and are relevant and authentic.

This new award singles out 95 organizations that, like 23andMe, have inspired people and given them compelling reasons to care about innovation, or social issues, cultural issues, the environment, or their fellow humans. Among those on the list are not just massive multinational conglomerates, but also small companies and nonprofits. All of them have forged an emotional or meaningful connection with people. All were judged on their relevancy, cultural impact, ingenuity, and business innovation.

"Fast Companyis excited to highlight companies and organizations that have built brands with deep meaning and connections to the customers they serve," said Stephanie Mehta, editor-in-chief of Fast Company. "At a time when consumers are holding companies to very high standards, businesses have much to learn from these brands that have garnered respect and trust."

Lead with Science

It's that trust that is probably most important to 23andMe's brand, said Tracy Keim, Vice President of Consumer Marketing and Brand at 23andMe.

"It started with Anne Wojcicki, (23andMe's CEO and Co-Founder)," Tracy said. "She co-founded 23andMe to help people - to be a brand that made a difference in people's lives - we were a brand born out of purpose, not profit."

23andMe is also a brand driven by science. And Fast Company pointed to two of our more recent very large scientific initiatives in singling out 23andMe for this award.

The first was a study using genetics to look at the human impact of the transatlantic slave trade, as part of the largest study to date of people with African ancestry in the Americas. The second is an ongoing study on the genetics associated with differences among people in susceptibility to and severity from COVID-19that involved more than a million research participants. Several findings from that study have already been published or shared, and our researchers are currently investigating the genetics of COVID-19 "long-haulers."

"It's exciting to see this list of brands making a difference," said Tracy. "We're all interested in solutions through action, not just advertising. One of 23andMe's core values is to 'lead with science.' DNA data can tell us so much about problems we confront today and in the future - whether it's studying COVID-19 or our fraught racial history, or important health issues - our team of researchers have big hearts and open minds and go where the science leads them."

Mission Driven

It's been almost two decades since the mapping of the human genome, the most significant scientific breakthrough of our generation. 23andMe works to bring the power of genetic science to everyone. As a brand, 23andMe has always been mission-driven, focused on helping people access, understand, and benefit from the human genome. We created an industry offering people direct access to their genetic information, as well as an opportunity to participate in research if they choose. We share our research findings and ensure that those who participate in research know we've done it through solid science and innovation, but also with whimsy and a human touch.

You can find a complete list of winnershere.

23andMe will be featured along with the other honorees in theNovember issue of Fast Companymagazine, which is available onlinenowand will be on newsstands beginning November 2, 2021.

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23andMe Honored in Fast Company's First Annual List of Brands That Matter - Marketscreener.com

Shahid Akhter, editor, ETHealthworld, spoke to Tony Jose, Co founder and CEO, Clevergene, to know more about current trends in Genomics and the opportunities it offers amidst challenges in India.

Genomics MarketGenomics is a comparatively new field, it has been just 10 years since this field has come into existence. If you really look at the Indian Market for Genomics, its just about 500 cr. This comprises of the discovery genomics as well as the Genetic Diagnostics which is driven by genomics.

If you really look back, 5 years, Genetics was really nonexistent with about 2-3 players, but today we have about 13-14 companies that are operating in this space, both in the discovery genomics as well as the genomics driven diagnostics space. Of these companies, we have 3-4 companies which have the capability and infrastructure to lead this space.

The universities and the academia should also develop the skills that are important for driving this whole industry. When I talk about the skillsets, I am talking about an interdisciplinary team of molecular biologist, Geneticist genomics experts, statisticians and such being trained and given to the industry.

There are mixtures form various races throughout our history and that also gives us a background for looking for Biomarkers to drive diagnosis for personalized medicine and even for drug development so I believe that the country should really grab the opportunity and work towards making India the leader in Genomics for the world.

Clevergene: Journey so farI started my career as a genomics scientist with training at Delhi university. I also had the opportunity to establish the very first high thruput DNA sequencing lab in the country and managed that for about 4 years. This was before I really understood the potential of this field and thought about starting myself. Back in 2013 I didnt have the wherewithal to start a full-fledged genomics laboratory and therefore I started a consulting firm and slowly and steadily we started this company by attracting highly talented individuals. We all come with a basic foundation in human genetics, and this gives us a uniqueness in driving this whole field.

Initially we got into certain strategic tie-ups with publicly funded academic institutions which gave us the infrastructure that is required. We went on to acquire another company which was reasonably funded by equity swapping which gave us the infrastructure that we were looking for and then we built this whole organization to a stage where in Clevergene can boast of being one of the top 3 genomics companies in India in terms of capability as well as capacity.

Within Clevergene we do have 2 business verticals. Genomics has two aspects to it one is in the discovery of novel biomarkers, where we work with academic institutions and Pharma companies that need high end DNA analysis for a particular project for e.g. they are looking for particular biomarkers for breast cancer or identifying biomarkers that can personalize certain cancer treatments etc. and on the other hand we have an applied genomics vertical, we call it The Gene Lab which focusses on diagnosis of pediatric genetic ailments.

There are about 10000 known genetic disorders categorized by the WHO. But the interesting fact is that if you take all of them individually, they are all rare, the incidence rate would be 1 in 10,000 or 1 in 20,000. But if you combine all of them together, we have about 1.6 mn children who are born with any of these disorders every year and there is a huge opportunity gap, or there is a huge gap in diagnosing these disorders.

So The Gene Lab focuses in providing comprehensive genomics based diagnosis for these diseases so that the doctors can manage the patient and even pro-actively prevent the birth of children with genetic disorders in the future.

Clevergene: Future plansSo the roadmap for Clevergene has been discovery diagnostics, screen, prevent and cure. So we have already established ourselves in the discovery genomics field. We are establishing ourselves in the genetic diagnostics field and as we move forward we will expanding our verticals into genetic screening where we are looking at Non-Invasive Genetic Pre-Natal Testing to identify genetic anomalies in fetus. We are also developing a carrier screening method where in the prospective parents can screen and check their carrier status for genetic disorders and therefore identify their risk of passing on a genetic disorder to the child and also look at alternative preventative methods for preventing such events in the future. The active preventative screening would be the way forward for Clevergene so that we together can eradicate many of these rare genetic disorders from the face of the earth.

In a longshot we are also looking at the development of technologies in the space of genome editing, genetic engineering etc. which should provide us with the power to edit a patients genome and even correcting a genetic ailment.

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India holds a huge potential for driving the whole genomics industry: Tony Jose, Clevergene - ETHealthworld.com

Some people get severely sick with COVID-19. Others don't even notice they've caught the infection.

Understanding the role of genetic variants in infection outcomes could help prevent or treat infectious diseases by restoring deficient immunity.

Over the past months, several studies have shown that some genes are potentially involved in the congenital resistance some people have towards COVID-19.

Blood types and COVID resistance

For example, the authors wrote that evidence suggested that people with O type blood groups may be slightly more resistant than people with other blood types.

In vitro studies have identified candidate genes that might be involved in how SARS-CoV2 enters human cells and triggers the infection.

SARS-CoV-2 penetrates human cells by binding the ACE2 receptor, which sits in the cell's membrane.

Scientists have discovered that a rare variant located close to ACE2 confers protection against COVID-19.

The hypothesis is that the variant decreases ACE2 expression.

In other in vitro studies, scientists found that some human ACE2 polymorphisms (a gene is polymorphic if more than one allele occupies that gene's locus) bind the SARS-CoV-2 spike protein with different affinities.

The role of genetic variants

Historically, therapeutics for infectious diseases have focused primarily on the pathogen rather than the host.

The most common idea has been to prevent the disease by vaccinating against the pathogen or stop the infection by interfering with the pathogen using drugs.

Understanding the role of genetic variants in infection outcomes could help prevent or treat infectious diseases by restoring deficient immunity.

"These variants are of particular interest for two reasons," the authors wrote.

"First, they can provide a deep understanding of the essential biological pathways involved in infection with SARS-CoV-2.

Second, they will allow for the development of innovative therapeutic interventions to prevent or treat SARS-CoV-2 infection in others."

The proof of principle for this second reason has been provided by CCR5 - a genetic mutation occurring in roughly one per cent of the population, which prevents HIV from binding to the surface of white blood cells.

Medicine mimicking genetics

After discovering CCR5, scientists developed an anti-retroviral drug called maraviroc, which mimics the effect of the mutation.

"No specific drug effective against COVID-19 has been discovered since the start of the pandemic," the authors wrote.

"Lessons learned [from genetics] could potentially guide us toward such specific treatments for COVID-19."

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A lucky few are unusually resistant to COVID-19. Scientists are trying to find a reason in their genes. - Mandurah Mail

Durban - Dr Aisha Pandor needed help around her house one December many years ago but could not find a trustworthy domestic worker quick enough.

Her frustration led the award-winning scientist with a PhD in Human Genetics and business management graduate, to co-found SweepSouth, the countrys first, on-demand cleaning app whichconnects busy people to trusted, background-checked cleaning professionals.

Pandors foray into the on-demand world of a business app came from her inherent curious personality and an enquiring mind that came from growing up in a family of successful and professional people.

Pandor, 36, was a guest speaker on a recent virtual webinar hosted by MANCOSA, a private higher education institution, where she provided students and graduates with practical tools and tips to successfully improve their employability and progress in their chosen career.

Explaining how she came up with the idea for SweepSouth, Pandor said one day during the December holidays some years ago, she was trying to look for a stand-in domestic worker to help out around the house, when she came up with the genius idea.

Pandor drew inspiration from online shopping and food delivery apps and together with her husband, they created the award-winning app.

She wanted to have greater interaction with people,and find out how best to organise domestic work and address the mutual needs of employers.

While studying for my PhD, I always thought about what type of work I would do and whether that work would be aligned with my purpose in life, she said.

The SweepSouth app was launched seven years ago, focusing on changing the mindset of home service professionals.The value of having supportive networks such as a partner, colleagues and family play an important role when having your own business, Pandor said.

She message to students and graduates was: you cannot be taught how to become an entrepreneur, but the skills learnt in courses will provide you with the confidence to become one.

The best learning comes from being able to do things on your own. Having self-confidence and learning to sell yourself by selling your product will be essential for entrepreneurship.

I learnt to become a source of strength and lead people through unforeseen circumstances such as the pandemic.

Entrepreneurship is challenging and there should be no shame in failing as long as you have tried your best and you are aware of the mistakes made and have learnt from them, she said.

Pandor said that success for her is living in the present and trying to make the best out of any day, whilst aligning her purpose in life and being of public service.

She said SweepSouth continues to be a platform that helps combat unemployment and underemployment by helping people find dignified jobs, and contribute to being the voice of women with no voice in public.

IOL

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Dr Aisha Pandor: How this award winning Human Genetics scientist developed an app to help keep your house clean - IOL

A widely accepted theory of Native American origins coming from Japan has been attacked in a new scientific study, which shows that the genetics and skeletal biology simply does not match-up.

The findings, published today in the peer-reviewed journal PaleoAmerica, are likely to have a major impact on how we understand Indigenous Americans arrival to the Western Hemisphere.

Based on similarities in stone artifacts, many archaeologists currently believe that Indigenous Americans, or First Peoples, migrated to the Americas from Japan about 15,000 years ago.

It is thought they moved along the northern rim of the Pacific Ocean, which included the Bering Land Bridge, until they reached the northwest coast of North America.

From there the First Peoples fanned out across the interior parts of the continent and farther south, reaching the southern tip of South America within less than two thousand years.

The theory is based, in part, on similarities in stone tools made by the Jomon people (an early inhabitant of Japan, 15,000 years ago), and those found in some of the earliest known archaeological sites inhabited by ancient First Peoples.

But this new study, out today in PaleoAmerica the flagship journal of the Center for the Study of the First Americans at Texas A&M University suggests otherwise.

Carried out by one of the worlds foremost experts in the study of human teeth and a team of Ice-Age human genetics experts, the paper analysed the biology and genetic coding of teeth samples from multiple continents and looked directly at the Jomon people.

We found that the human biology simply doesnt match up with the archaeological theory, states lead author Professor Richard Scott, a recognized expert in the study of human teeth, who led a team of multidisciplinary researchers.

We do not dispute the idea that ancient Native Americans arrived via the Northwest Pacific coastonly the theory that they originated with the Jomon people in Japan.

These people (the Jomon) who lived in Japan 15,000 years ago are an unlikely source for Indigenous Americans. Neither the skeletal biology or the genetics indicate a connection between Japan and the America. The most likely source of the Native American population appears to be Siberia.

In a career spanning almost half a century, Scott a professor of anthropology at the University of Nevada-Reno has traveled across the globe, collecting an enormous body of information on human teeth worldwide, both ancient and modern. He is the author of numerous scientific papers and several books on the subject.

This latest paper applied multivariate statistical techniques to a large sample of teeth from the Americas, Asia, and the Pacific, showing that quantitative comparison of the teeth reveals little relationship between the Jomon people and Native Americans. In fact, only 7% of the teeth samples were linked to the non-Arctic Native Americans (recognized as the First Peoples).

And, the genetics show the same pattern as the teethlittle relationship between the Jomon people and Native Americans.

This is particularly clear in the distribution of maternal and paternal lineages, which do not overlap between the early Jomon and American populations, states co-author Professor Dennis ORourke, who was joined by fellow human geneticists and expert of the genetics of Indigenous Americans at the University of Kansas, Jennifer Raff.

Plus, recent studies of ancient DNA from Asia reveal that the two peoples split from a common ancestor at a much earlier time, adds Professor ORourke.

Together with their colleague and co-author Justin Tackney, ORourke and Raff reported the first analysis of ancient DNA from Ice-Age human remains in Alaska in 2016.

Other co-authors include specialists in Ice-Age archaeology and ecology.

Shortly before publication of the paper, two other new studies on related topics were released.

A new genetics paper on the modern Japanese population concluded that it represents three separate migrations into Japan, rather than two, as previously believed. It offered more support to the authors conclusions, however, about the lack of a biological relationship between the Jomon people and Indigenous Americans.

And, in late September, archaeologists reported in another paper the startling discovery of ancient footprints in New Mexico dating to 23,000 years ago, described as definitive evidence of people in North America before the Last Glacial Maximumbefore expanding glaciers probably cut off access from the Bering Land Bridge to the Western Hemisphere. It remains unclear who made the footprints and how they are related to living Native Americans, but the new paper provides no evidence that the latter are derived from Japan.

Professor Scott concludes that the Incipient Jomon population represents one of the least likely sources for Native American peoples of any of the non-African populations.

Limitations of the study include that available samples of both teeth and ancient DNA for the Jomon population are less than 10,000 years old, i.e., do not antedate the early Holocene (when the First Peoples are understood to arrive in America).

We assume, the authors explain however, that they are valid proxies for the Incipient Jomon population or the people who made stemmed points in Japan 16,00015,000 years ago.

Human tissue samples

Peopling the Americas: Not Out of Japan

13-Oct-2021

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Popular theory of Native American origins debunked by genetics and skeletal biology - EurekAlert

Newswise LA JOLLA, CALIF. October 11 Researchers from Sanford Burnham Prebys have discovered a new source of stem cells just outside the liver that could help treat people living with Alagille syndrome, a rare, incurable genetic disorder in which the bile ducts of the liver are absent, leading to severe liver damage and death. The findings, published recently in the journal Hepatology,have extensive biomedical implications for Alagille syndrome and for liver disease in general, including cancer.

Weve been aware of the regenerative power of the liver for a long time, possibly even going back to the ancient Greek myth of Prometheus, says lead authorDuc Dong, Ph.D., an associate professor in theHuman Genetics Programat Sanford Burnham Prebys. But the existence and nature of liver stem cells remains an intensely debated topic.

The new study suggests that the reason these cells have been so hard to find may be that researchers have been looking in the wrong place.

The stem cells that we found are actually outside the liver, not within it, which may have made their discovery difficult, adds Dong. We think these outside the box liver stem cells act more like reserves, only traveling into the liver when all other options are exhausted. It only requires a few of these cells to enter the liver and multiply to repopulate all of the cells lost to the disease.

Over 4 thousand babies each year are born with Alagille syndrome, which is caused by a mutation that prevents duct cells from forming in the liver. And while the syndrome can occasionally resolve naturally, and there are treatments available to manage the symptoms, the disease is incurable, carrying a 75% mortality rate by late adolescence for those without a liver transplant.

"We have known and supported Dr. Dong for years and we feel the work he and his team have done on this disease to date is extraordinary," says Cher Bork, Executive Director of the Alagille Syndrome Alliance. "Hope can be difficult to come by for families dealing with any incurable disease, and discoveries like this help give that hope back to families living with this life-dominating condition."

Using zebrafish, which have many of the same genes and cellular pathways as humans, Dongs research team were able to create a model of Alagille syndrome by selectively deactivating genes associated with Alagille syndrome. These genes encode for chemical messengers from the Notch pathway, a signaling system found in most animals that is involved in embryonic development and adult cell maintenance.

Our work suggests that there is potential for liver regeneration in Alagille patients, but because this signaling pathway is mutated, the regenerative cells fail to fully mature into functioning liver duct cells, says Dong.

In further animal studies, the team showed that by genetically restoring this signaling pathway, the regenerative cells could remobilize to form liver ducts, restoring the function of the liver and improving survival. The researchers are now leveraging their discovery to develop new therapies for Alagille syndrome.

Weve shown not just that regeneration is possible in models of Alagille syndrome, but, importantly, how it can be enhanced, says Dong. These missing duct cells can regenerate if Jagged/Notch is restored, and our lab has developed the first drug that can boost this pathway.

While the new drug requires further studies to advance into clinical trials, the team has already found that it could enhance regeneration and survival in animal models and can trigger the Notch pathway in cells from Alagille patients. These results will be published in separate studies.

Were hopeful that this drug will restore the regenerative potential of the liver in Alagille patients, to be more like the liver of Prometheus, adds Dong.

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About Sanford Burnham Prebys Medical Research Institute

Sanford Burnham Prebys is a preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology and childrens diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us atSBPdiscovery.orgor on Facebookfacebook.com/SBPdiscoveryand on Twitter@SBPdiscovery.

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New stem cell identified by Sanford Burnham Prebys researchers offers hope to people with rare liver disease - Newswise