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Genetics

Podcast: Polymerase chain reactionThe ‘transformative’ tool that sparked a genetics revolution – Genetic Literacy Project

Geneticist Dr. Kat Arney revisits the story and the characters behind one of the most transformativeand ubiquitous techniques in modern molecular biology: the polymerase chain reaction (PCR), on the latest episode of the Genetics Unzipped podcast from the Genetics Society.

Anyone who has worked with DNA in the laboratory is undoubtedly familiar with PCR. Invented in 1985, PCR is an indispensable molecular biology tool that can replicate any stretch of DNA, copying it billions of times in a matter of hours, providing enough DNA to use for applications like forensics, genetic testing, ancient DNA analysis or medical diagnostics.

Its hard to overstate the transformation that PCR brought to the world of molecular biology and biomedical research. Suddenly, researchers could amplify and study DNA in a way that had been simply impossible before, kickstarting the genetics revolution thats still going strong today.

So where did this revolutionary technology come from? Officially, PCR was invented in 1985 by a colorful character named Kary Mullis, who won a Nobel Prize for the discovery. But, as well see, all the components of PCR were in place by the early 1980s thanks to the work of scientists like Arthur Kornberg and Har Gobind Khoranait just took a creative leap to assemble them into one blockbusting technique.

Then, the discovery of Thermus aquaticus in the hot springs of Yellowstone National Park by Thomas Brock in the 1960s, the isolation of the thermostable Taq polymerase from that bacterium in 1976 by Alice Chien and John Trela from the University of Cincinnati, and the subsequent invention of automatic thermocyclers paved the way for the simple, one-step PCR process that has transformed laboratories across the world.

Full show notes, transcript, music credits and references online at GeneticsUnzipped.com.

Genetics Unzippedis the podcast from the UKGenetics Society,presented by award-winning science communicator and biologistKat Arneyand produced byFirst Create the Media. Follow Kat on Twitter@Kat_Arney,Genetics Unzipped@geneticsunzip,and the Genetics Society at@GenSocUK

Listen to Genetics Unzipped on Apple podcasts (iTunes), Spotify, or wherever you get your podcasts.

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Podcast: Polymerase chain reactionThe 'transformative' tool that sparked a genetics revolution - Genetic Literacy Project

Genetics

Largest Study To-Date Focused on Undiagnosed Genetic Disease Patients Reveals That Bionano’s Optical Genome Mapping Technology Can Diagnose…

SAN DIEGO, Nov. 05, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced the publication of a study led by scientists and clinicians from the Institute for Human Genetics and the Benioff Childrens Hospital at the University of California, San Francisco (UCSF) that evaluated the ability of Bionanos optical genome mapping technology and another genome analysis method to diagnose children with genetic conditions who previously went undiagnosed by the standard of care methods alone. Of the 50 children in the study, the optical genome mapping results were sufficient to definitively diagnose 6 patients (or 12%) and, for another 10 patients (or 20%), the Bionano data revealed candidate pathogenic variants. Upon further analysis, it is expected that an additional 3 patients could be diagnosed with the Bionano data, bringing the total of definitively diagnosed patients to 9 (or 18%).

Erik Holmlin, Ph.D., CEO of Bionano Genomics commented, Increasing the number of patients who receive a definitive molecular diagnosis is the driving force behind much of the development of new diagnostic technologies. Every major change in medical guidelines connected to introducing novel methods has been driven by the ability of new methods to diagnose more patients than the previously existing standard of care. This study by the UCSF team shows that Bionanos optical genome mapping can potentially bring another such leap to the clinic by diagnosing many more patients than what existing chromosomal microarray (CMA) and whole exome sequencing (WES) can. Several studies released this year have shown that Saphyr can detect all clinically relevant variants identified by karyotyping, microarray and FISH in both leukemias and genetic disease cases. This UCSF study now shows in the largest cohort analyzed to date that Bionanos optical genome mapping diagnoses more patients than the traditional methods. We believe the increase in diagnosis over conventional methods can be a significant factor in Saphyr gaining widespread adoption as a clinical tool for genetic disease diagnosis and next-generation cytogenomics.

As described in the publication, the UCSF team performed full genome analysis by combining optical genome mapping with Bionano technology and linked-read sequencing on 50 undiagnosed patients with a variety of rare genetic diseases and their parents to determine if this full genome analysis method could help solve cases that had not been diagnosed with previous testing. Of the 50 cases, 42 were previously analyzed by CMA, the first tier medical test for genetic disease cases, and 23 had previously been analyzed with commercial trio whole exome sequencing, and no pathogenic or likely pathogenic variants were identified by these methods.

Bionanos optical genome mapping technology identified a number of pathogenic variants unidentified by CMA and undetectable by WES, including duplications and deletions that were too small to be identified by CMA, or occurred in regions of the genome not typically covered by CMA or WES. Of the additional 7 patients with variations considered to be candidates for pathogenic variants, the findings included deletions, duplications, and inversions. Before concluding that these variants are sufficient to diagnose the patients, further analysis is required since these variants had not previously been reported in patients with similar disease.

The publication is available at: https://www.medrxiv.org/content/10.1101/2020.10.22.20216531v1A recording of the webinar is available at: https://bionanogenomics.com/webinars/optical-mapping-in-rare-genetic-disease-diagnosis/

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visitwww.bionanogenomics.com or http://www.lineagen.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the contribution of Bionanos technology to the diagnosis of more genetic disease patients when compared to traditional standard of care methods; the capabilities of Bionanos technology in comparison to other genome analysis technologies; our expectations regarding the adoption of Saphyr as a clinical tool for genetic disease diagnosis and next-generation cytogenomics; and Bionanos strategic plans. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, PhDLifeSci Communications+1 (617) 733-7668darren@lifescicomms.com

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Largest Study To-Date Focused on Undiagnosed Genetic Disease Patients Reveals That Bionano's Optical Genome Mapping Technology Can Diagnose...

Genetics

Race, genetics, and their impact on health – Mumbai Mirror

Amongst the various forms of discriminations the world has seen, Apartheid, a system of institutionalised racial segregation practised in South Africa, was one of the worst. I went to medical school with several South African students and the stories of discrimination they told me about were horrifying. Thankfully Apartheid, which was based on white supremacy and lasted more than 40 years, ended in the early 1990s.

I am often asked by my Caucasian friends if I felt discriminated against in the UK because of my brownness. I reply that it may have been true in early 1970s. I remember waiting in line to be served a pint of beer, only to be ignored by the proprietor of the pub. When I had the good fortune of going with a white girl, there was never a problem getting served.

Of course things have changed in the UK, which is today a proudly multicultural country. Overt discrimination of the kind that existed earlier is no longer tolerated. Asian communities especially are a thriving group, eagerly courted by political parties. Today when I go to a pub in London, I find the barmaid waiving me in.

This brings us to the topic of todays column: the role of race in health outcomes. Differences in health status, life expectancy and other indicators in different racial and ethnic groups are well documented. But before we get to that, let me get a somewhat controversial subject out of the way: the dominance of black athletes.

Black athletes enjoy a huge over-representation at the highest level of many sports - from the 100 metres sprint through to the marathon, every single record is currently held by athletes of African origin.

Sir Roger Bannister, who ran the first sub-4-minute mile, said in a speech to the British Association of Advancement of Science in 1995 that heel-bone length, subcutaneous fat and differences in the length of the Achilles tendon may explain the advantage that Africans may have in running sports. A study published in the Journal of Applied Physiology reported that Africans display an enhanced resistance to fatigue while running on a treadmill. There are tens of such studies - many of them controversial - which are beyond the scope of one column.

Coming back to race and health outcomes: Diabetes, for example, is 60 per cent more common among African Americans than white Americans. Black Americans are 2.5 times more likely to suffer limb amputations and 5.5 times likely to suffer from kidney disease because of diabetes.

Blacks in America are more likely to die of asthma than whites and, despite lower tobacco exposure, Blacks are 50 per cent more likely to get lung cancer.

Black Americans suffer twice the risk of stroke than Whites; strokes kill four times more 35- to 54-year-old Blacks than white. Black men have a 40 per cent high cancer death rate, and women 20 per cent higher death rate, than their white counterparts.

The stats for the other major minority group in America - the hispanics - are similarly depressing.

Around 15 years ago, the US FDA controversially approved a drug called BiDil for a single racial-ethnic group - African Americans - for treatment of congestive heart failure. The scientific research leading to BiDils approval tested the drug only in African American populations.

Craig Venter, the famous American biotechnologist who produced the map of the human genome, said it was disturbing to see things categorised in terms of race.

Is race really a surrogate marker for describing human genetic variation? In India genetics and race are certainly considered interchangeable. People still prefer getting married to someone of their own community. One of the major consequence of endogamy - the practice of marrying within the same community - is genetic diseases arising out of a limited gene pool. We would certainly be better off if we looked to widen our gene pool.

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Race, genetics, and their impact on health - Mumbai Mirror

Genetics

Your Dog Could Have the Same Genetic Makeup as Canines Living During the Ice Age – Yahoo Lifestyle

Your Dog Could Have the Same Genetic Makeup as Canines Living During the Ice Age

There are at least five types of dogs that have DNA tying to breeds from 11,000 years ago, according to a new study.

Is your dog your very best companion? We understand. There's a good reason that canines are said to be a man'sor woman'sbest friend. But just how long exactly have dogs been around? A group of researchersconsisting of scientists from the Francis Crick Institute, the University of Oxford, the University of Vienna, and archaeologists from over 10 countriespublished a study in the journal Science that just gave their answer. According to the article, titled "Origins and Genetic Legacy of Prehistoric Dogs," the team dug deep to discover that the genetic makeup of the modern dog traces back to the end of the Ice Agewhich means your dogs are actually connected to some of the most ancient pet species, CNN reports.

Hillary Kladke / Getty Images

To come to their findings, the scientists studied the DNA from ancient dog bones. From there, they found that there were five types of dogs with specific genetics that came out of the Ice Age. These dogs have "mixed and combined" lineages that are still found in the everyday dog today. The researchers uncovered that Rhodesian ridgebacks have ties to DNA from an ancient Middle Eastern or African lineage, Siberian huskies have genetic makeup from an ancient Siberian lineage, and dogs like chihuahuas and Mexican hairless dogs have some pre-Columbian DNA.

Related: The Most Low-Energy, Non-Shedding Dog Breeds

Anders Bergstrom, the lead author and post-doctoral researcher in the Ancient Genomics Laboratory at London's Francis Crick Institute, also shared that canines have been housebroken and found worldwide for some time now. "Already by 11,000 years agobefore agriculture, and before any other animal had been domesticateddogs had not only been domesticated, but they had already diversified genetically and likely spread across large parts of the world."

Bergstrom added, though, that the mixing of DNA is common in dogs. "All dog breeds from Europe share a common history that started with an ancient mixture, many thousands of years ago, between two very distinct dog lineagesone related to dogs in the Near East, and the other related to dogs in Siberia. This ancient mixing event between these two lineages gave rise to the European dog gene pool which later would give rise to all present-day European dog breeds," he said. "We find that when we compare the history of dogs to the history of humans, to a quite large degree they mirror each other, suggesting that in many cases, the history of dogs has been shaped by humans. In many cases humans would simply bring their dogs with them as they migrated and moved across the world."

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Your Dog Could Have the Same Genetic Makeup as Canines Living During the Ice Age - Yahoo Lifestyle

Genetics

Scientists Assemble Full Genomes for Domesticated Apple and Two of Its Wild Progenitors – Technology Networks

The fabled Silk Road - the 4,000-mile stretch between China and Western Europe where trade flourished from the second century B.C. to the 14th century A.D. - is responsible for one of our favorite and most valuable fruits: the domesticated apple (Malus domestica).

Snack-packing travelers would pick apples at one spot, eat them and toss their cores many miles away. The seeds grew into trees in their new locations, cross-bred with the wild species, and created more than 7,000 varieties of apples that exist today.

Hybridizations with wild species have made the apple genome very complex and difficult to study. A global team of multi-disciplinary researchers - co-led byZhangjun Fei,faculty member at Boyce Thompson Institute (BTI), andGan-Yuan Zhong, scientist with the USDA-Agricultural Research Service (ARS) in Geneva, New York - tackled this problem by applying cutting-edge sequencing technologies and bioinformatics algorithms to assemble complete sets of both chromosomes for the domesticated apple and its two main wild progenitors.

The researchers discovered that the apple's unique domestication history has led to untapped sources of genes that could be used for crop improvement, such as improving size, flavor, sweetness and texture.

"Plant breeders could use this detailed information to improve upon traits that matter most to consumers, which today is primarily flavor," says Fei, also an adjunct associate professor in Cornell University's School of Integrative Plant Science (SIPS).

"Perhaps more importantly," he added, "the information will help breeders produce apples that are more resistant to stress and disease."

The research is described in apaperpublished inNature Geneticson November 2, with authors from BTI, Cornell University, Cornell AgriTech, the U.S. Department of Agriculture (USDA) and Shandong Academy of Agricultural Sciences.

Follow-up discussions among Fei, Zhong and other colleagues at Cornell, inspired them to build better and new apple reference genomes by applying new sequencing and assembly technologies to material in USDA's Geneva Clonal Repository. The repository, which is housed atCornell AgriTech, holds the largest collection of apple accessions in the world. Many of these accessions can be traced back to the Silk Road.

In the current work, the researchers sequenced, assembled and compared the full reference genomes for three species: Gala, a top commercial cultivar of M. domestica; and apple's two main wild progenitors, the European crabapple (M. sylvestris) and the central Asian wild apple (M. sieversii), which together account for about 90% of the domesticated apple's genome.

The results provide apple breeders with detailed genomic roadmaps that could help them build a better apple.

"We wanted to develop new genomes, especially the wild progenitors, because of the tremendous impact they could have on understanding apple's genetic diversity and identifying useful traits for breeding new cultivars," said Zhong, who is also an adjunct associate professor in SIPS.

By comparing the three genomes, the researchers were able to identify which progenitor species contributed the genes responsible for many traits in the domesticated apple. For example, the team found that the gene giving apple its crunchy texture is located near the gene that makes it susceptible to blue mold.

"Now that we know exactly where those two genome regions are," Fei said, "breeders could figure out a way to keep the texture gene and breed out or edit out the blue mold gene to produce a more disease-resistant cultivar."

The team identified about 50,000 genes in the pan-genome of the domesticated apple, including about 2,000 that were not present in previously published reference genomes for apple species. "These 'missing genes' turn out to be really important, because many of them determine the traits of greatest interest to apple breeders," Fei said.

Using RNA extracted from different stages of Gala fruits, they also identified genes linked to texture, aroma and other fruit characteristics that were preferentially expressed between the two copies of the genes.

"That provides us and breeders with an even deeper understanding of the genetic diversity underlying a particular trait," Zhong said. "The findings will help our group better manage and curate more than 6,000 apple accessions in the USDA Geneva Clonal Repository," Zhong adds, "as well as enable us to provide critical genetic and genomic information associated with the accessions to breeders and other researchers."

Reference: Sun X, Jiao C, Schwaninger H, et al. Phased diploid genome assemblies and pan-genomes provide insights into the genetic history of apple domestication. Nature Genetics. 2020. doi:10.1038/s41588-020-00723-9.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Scientists Assemble Full Genomes for Domesticated Apple and Two of Its Wild Progenitors - Technology Networks

Genetics

Benchmark : Genetics has signed a 5-year ova agreement with AquaCon – Marketscreener.com

3 November 2020

The contract between Benchmark Genetics and AquaCon involves deliveries of genetics to the land-based facilities that AquaCon are planning to build in Maryland, USA. Benchmark's Icelandic company, StofnFiskur, will supply approximately 40 million ova to AquaCon over five years. The agreement confirms and consolidates Benchmark's strong position as a genetics supplier to land-based farming worldwide.

Benchmark Genetics has been producing land-based broodstock and ova in Iceland since the early 1990s and has long-standing experience with land-based salmon farming worldwide. Geir Olav Melingen, Commercial Director at Benchmark Genetics, considers this a clear competitive advantage when selling to new land-based projects:

'As a leading supplier to land-based farming, we have gradually gained comprehensive experience in securing deliveries to destinations all over the world. Since we keep our broodstock on land and thereby have full control over the maturation and spawning, we are in the position to produce and deliver ova to customers every single week of the year. The term 'egg season' is outdated with us'.

Security of supply was an essential factor for why AquaCon chose the company as a supplier.

Pl Haldorsen is the CEO of AquaCon, which currently has a head office in Oslo and shortly plans to go public. 'We have chosen to secure genetics at an early stage, as we consider ova as a key strategic success factor of our ambitious growth plans', he says.

Haldorsen explains that Benchmark Genetics satisfies AquaCon's requirements for the security of supply, biosecurity and genetic traits adapted to land-based RAS farming:

'Our production plan presupposes regular deliveries of ova throughout the year, and Benchmark Genetics has a production model for land-based broodstock that makes us confident that we will receive deliveries following our plans'.

Located on the south-west shore of Iceland, StofnFiskur's land-based facilities have no other salmon farms nearby. The intake water, both freshwater and seawater, comes from boreholes and is entirely pathogen-free. StofnFiskur's four farms are approved according to the OIE compartment standard, meaning that the zones around each farm are defined as entirely isolated and protected from external disease threats. As an example, Benchmark Genetics is the only genetics company approved by Sernapesca for export of ova to Chile.

'The unique location and production model makes us confident that we can deliver eggs that have the highest biosafety standard to AquaCon,' says Geir Olav Melingen.

Geir Olav also proudly says that all energy used for broodstock and ova production in Iceland comes exclusively from renewable sources. Thus, the production has a relatively low CO2 footprint, even though land-based production is often considered energy-intensive.

Benchmark Genetics strongly believes that significant parts of the future growth in salmon farming will come from land-based production. Therefore, the company has developed production concepts and products that are adapted to the specific needs of this part of the industry.

'The genetic weighting of growth and quality traits forms the foundation of our product, SalmoRAS4 +. Besides, we have also developed methods in the production of broodstock that produce offspring that will not become sexually mature. This means that the operations like AquaCon can produce at higher temperatures to optimize growth', says Melingen.

'We, therefore, have great faith that land-based farming in the future will be competitive on production costs compared to traditional sea-farming', Geir Olav Melingen concludes.

Disclaimer

Benchmark Holdings plc published this content on 03 November 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 03 November 2020 09:34:02 UTC

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Benchmark : Genetics has signed a 5-year ova agreement with AquaCon - Marketscreener.com

Genetics

Study reveals complex and vast diversity of African genetic variation – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Oct 29 2020

The study, in which six Wits researchers were involved, show that these newly discovered variants were found mostly among newly sampled ethnolinguistic groups.

Researchers identified new evidence for natural selection in and around 62 previously unreported genes associated with viral immunity, DNA repair and metabolism.

They observed complex patterns of ancestral mixing within and between populations, alongside evidence that populations from Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations.

These findings improve the current understanding of migration across the continent, and identify responses to human disease and gene flow as strong determinants of population variation.

The study contributes a new major source of African genomic data, which showcases the complex and vast diversity of African genetic variation and which will support research for decades to come.

Africa is the continent with greatest genetic diversity and this study shows the importance of African genomic data for taking science and health research forward. It is an important step in redressing existing biases in available data for research, which hamper the study of African health problems and narrows global research."

Zan Lombard, Study Senior Author and Associate Professor, Division of Human Genetics in the Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service

Lombard led the study under the auspices of the Human Heredity and Health in Africa (H3Africa) Consortium in association with Dr Neil Hanchard, Baylor College of Medicine, Texas, U.S.A, and Dr Adebowale Adeyemo, National Human Genome Research Institute, Maryland, U.S.A.

Members of the H3Africa Consortium who contributed to this work comprise people from 24 institutions across Africa, including the Sydney Brenner Institute for Molecular Bioscience (SBIMB) in the Faculty of Health Sciences at Wits University.

The SBIMB's Dr Ananyo Choudhury, Dr Dhriti Sengupta, Professor Scott Hazelhurst and Mr Shaun Aron led analyses and writing the paper, while Professor Michle Ramsay, director of the SBIMB, participated in developing the study design and was a principal investigator who contributed samples towards this large-scale sequencing effort.

The study found a vast breadth of genomic diversity among these genomes, with each ethnolinguistic group harbouring thousands of unique genetic variants.

Not only populations from the same geographic region but even those from the same country showed a great deal of variation among themselves, reflecting the deep history and rich genomic diversity across Africa.

"We used a wide variety of computational techniques to gain insights into population history, environmental adaptation, and susceptibility to diseases from these genomes", says Choudhury, first author of the study and a senior scientist at the SBIMB.

"We were able to discover over 3 million novel variants within these genomes. This was after comparison with more than 1000 African genomes in public repositories, suggesting that the potential for discovering novel genetic variants by sequencing African populations is still far from saturation."

First evidence of East Africa to Nigeria migration 50+ generations ago

In addition to contributing to the vast amount of novel variation observed in African populations, the inclusion of previously unstudied population groups in the study enabled scientists to add puzzle pieces to the jigsaw of established historical interactions and migration events on the continent.

"Inclusion of novel African genomes in our study strongly supported Zambia as an intermediate site in the Bantu-migration route to the South and East of the continent," said Mr Shaun Aron, lead analyst on the population genetics component of the study and a lecturer in the SBIMB.

Evidence supporting movement from East Africa to central Nigeria between 1500 and 2000 years ago was revealed through the identification of a substantial amount of East African ancestry, particularly Nilo-Saharan from Chad, in a central Nigerian ethnolinguistic group, the Berom.

"This highlights the complex historical movement of people on the continent and diversity of even proximally close African groups," says Aron.

The researchers found more than 100 areas of the genome that had probably been under natural selection; a sizable proportion of which were associated with immunity related genes.

Natural selection - "selected by nature" - comes from Charles Darwin's work into survival of the fittest. It means that when individuals are exposed to certain environmental factors (diet, viral infection, etc.) some gene variants may give the humans that bear them in their genome an added advantage to survive.

"While genes involved in resistance to insect-transmitted diseases like malaria and sleeping sickness have long been known to be positively selected, our study shows that other viral infections could have also helped to shape genomic differences between people and groups by altering the frequency of genes that affect individuals' disease susceptibility," says Dr Dhriti Sengupta of the SBIMB and one of the lead analysts.

Also, the selection signals were not homogenous across the continent. Sengupta says, "There were noticeable variations in selection signals between different parts of the continent, indicating that large-scale local-adaptations might have accompanied the migration of populations to new geographies, and consequent exposure to new diets and pathogens."

Selection signals are parts of the genome that give us a signature (signal) that the specific part of the genome was under selection pressure at some point.

Lombard, a senior author on the paper and an Associate Professor in the Division of Human Genetics at Wits, says: "The findings have broad relevance, from population genetics research into human history and migration, to clinical research into the impact of specific variants on health outcomes".

Immediate next steps include further examination of the initial findings and leveraging the data to represent more African populations.

The researchers hope their work will lead to wider recognition of the extent of uncatalogued genomic variation across the African continent and the need for continued inclusion of the many diverse populations in Africa in genomics research.

"Adding genomic data from all global populations - including Africa - is essential to ensure that everyone can benefit from the advances in health that precision medicine offers," says Lombard. Precision medicine - or 'personalised' medicine - refers to disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.

The study represents a major milestone in advancing African genomics research capacity. Instead of African data being analysed elsewhere - as has been the general trend over the last decade - this research was conducted predominantly by local African researchers using local computational facilities.

Studies like this one highlight the importance of computing infrastructure and storage capacity for large data projects at Wits and in South Africa.

Infrastructure such as the computing cluster at Wits, established and managed by Professor Scott Hazelhurst, director of Wits Bioinformatics, is essential to support genomics research and growing African datasets. He says: "Initiatives such as the H3Africa Consortium have laid the foundation to foster and encourage collaborative research in Africa, which has made studies like these possible."

Professor Michle Ramsay, director of the SBIMB, says: "This study, in a sense, announces the availability of both infrastructure and analytic skills for large-scale genomics research on the continent."

Source:

Journal reference:

Choudhury, A., et al.(2020) High-depth African genomes inform human migration and health. Nature. doi.org/10.1038/s41586-020-2859-7.

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Study reveals complex and vast diversity of African genetic variation - News-Medical.Net

Genetics

Experts Say One Of Largest Federal Genetics Study In History Could Leave People Of Color Behind – KPBS

In 2009, when Los Angeles resident Estela Mata was 35 years old, her sister, Juana Mata, was diagnosed with lupus.

And we didn't know what lupus was back then. It wasn't really talked about a lot. And she literally almost died, Estela Mata said.

Aired 10/26/20 on KPBS News

Listen to this story by Shalina Chatlani.

The Mata family moved to the U.S. when she was just a child. And her mother, who didnt speak English well, had to learn quickly about the disease. But, treatments for lupus were hard to find. The rare genetic disease still doesnt have a cure.

When we found out that lupus was genetic, we're like, oh, my gosh, like we need to get more involved into clinical trials, she said.

Estela Mata and her sister found a National Institutes of Health (NIH) clinical trial called the All of Us Research Program and enrolled in Los Angeles. She now works for the program with Scripps Research Institute in San Diego.

The 10-year $1.5 billion tax-payer funded program started enrolling patients in 2018, with the goal of collecting genetic information of 1 million people across the United States.

Half of that genetic information will come from "racial or ethnic minorities." The objective is to rectify a decades-long problem: most clinical trials have only collected data on white men, and not Latinas like the Matas.

We're talking about precision medicine, right? So, if you have this illness, take this medication or this treatment plan. It's not customized to the individual especially in the Hispanic community, we wanted to make sure that we were included, Estela Mata said. She consented to giving her genetic information because she believes it will be used to help low-income people of color receive treatments that could help them.

Colonized Science Means People Of Color Are Often Left Behind

But, some genetics experts say, the All of Us program is not really for all of us.

You can't really talk about science in America without talking about colonialism. We use bodies to derive data, said Keolu Fox, an anthropologist at UC San Diego.

In terms of underrepresented people being ... validated or recognized in science, that's kind of unfortunate because there aren't enough Ph.D. carrying brown, Black, indigenous people to represent our interests.

Fox, who grew up in Hawaii, got into genetics because he wanted to study why people with his indigenous heritage are more prone to develop certain diseases. But throughout his career, he says he found that people of color are often exploited in science.

And he says that exploitation will happen with the All of Us study. The data is open to everyone.

Is it actually going to benefit indigenous, Black and brown communities in the same way that it's going to benefit a handful of people that work for Pfizer, Merck, GSK, et cetera? I don't think so, he said.

Fox says big data, including digital and genetic data from humans, has become one of the most valuable commodities on Earth. One report from Global Market Insights found that the global digital genome market value is expected to cross $50.4 billion by 2025, a doubling from its value in 2018.

What key genetic mutations have allowed humans to subsist in the harshest, most remote environments on planet Earth? And can those signatures of natural selection lead to therapeutic value? he said. We're talking about deriving genetic information from populations that have been in sync with their land and characteristics that they earned through their diaspora, through natural selection.

Precedent For Expensive Treatments

Arizona State University biomedical historian Ben Hurlbut says exploitation of people of color and underserved communities happened before in medicine. In the 1990s, a lot of academic researchers started teaming up with rare disease groups to identity genes causing disease.

The academic researchers would patent the gene and control diagnostics and drug development without the involvement of the rare disease group who brought them the resources to do the research in the first place, said Hurlbut.

In fact, after scientists discovered the gene causing cystic fibrosis in 1989, a rare disease group and NIH funded researchers partnered to study the condition. Vertex Pharmaceuticals used the decades of research to create a therapy that could help 90% of patients.

But the treatment costs around $300,000 a year.

When that drug came out, one of my daughters best friend had cystic fibrosis and was a candidate for that drug. His mom took on a full-time job in order to pay for the drug like that was the sole purpose of her job was to pay the copay, said Hurlbut.

The solution to unequal health-care access isnt easy, he says that doesnt mean it can be ignored. Especially when to date, more than 270,000 people have gone through All of Us.

We as a society and a public put in place the regulatory structures, the public research investment, the market structures that produce the dynamics that we have, Hurlbut said.

We could change those tomorrow if there was the political will to do so.

Solutions Aren't Easy

Pharmaceutical companies are working on the All of US study. Alyssa Cotler, a spokeswoman for the program, says participants get information before they consent. And she says private-public partnerships are productive. Theyve led to life saving therapies.

It really is important to bring together all of these different voices and resources to make sure that we're building a resource that will really be available to answer this very ambitious call, Cotler said.

She says the data has been made anonymous and theres a code of conduct that researchers have to follow in order to get the data. She says the NIH is aware future treatments from the program may be unaffordable. But, she said the NIH doesnt have an answer to that problem yet.

We think that the goal of our program is really to ensure that we can accelerate these breakthroughs so that everybody has access to the outcomes. And it's important to us that we have diverse representation, that we have people who have not been included in research in the past so that the findings will be relevant to everybody, Cotler said.

We want to ensure that they have access to those treatments. So, it's an area of ongoing conversation that I think is not very simple to answer in an easy way. There have been a lot of conversations with different communities to really help us think this through, Cotler said.

As for All of Us participant Estela Mata, she says shes OK with the idea of her data going to a pharmaceutical company, if people like her sister, who need the therapies, will be able to afford them.

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Experts Say One Of Largest Federal Genetics Study In History Could Leave People Of Color Behind - KPBS

Genetics

Study suggests a role for the hypothalamus in genetic susceptibility to IBD – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Oct 29 2020

Using sophisticated 3D genomic mapping and integrating with public data resulting from genome-wide association studies (GWAS), researchers at Children's Hospital of Philadelphia (CHOP) have found significant genetic correlations between inflammatory bowel disease (IBD) and stress and depression. The researchers went on to implicate new genes involved in IBD risk that are enriched in both derived hypothalamic neurons, from a part of the brain that has a vital role in controlling stress and depression, and organoids derived from colon cells, a region more commonly studied in the context of IBD.

The findings were published in Cellular and Molecular Gastroenterology and Hepatology.

Our results implicate a role for the hypothalamus in the genetic susceptibility to IBD. Epidemiological data has previously shown overlap between IBD and stress and depression, and now we have generated genomics data to support that association. Our results suggest that the hypothalamus warrants further study in the context of IBD pathogenesis."

Struan Grant, PhD, senior author, director of the Center for Spatial and Functional Genomics at CHOP and the Daniel B. Burke Endowed Chair for Diabetes Research

IBD, which includes both Crohn's disease (CD) and ulcerative colitis (UC), is principally an immune-mediated condition characterized by dysregulated inflammation of the gastrointestinal tract. The disease course ranges from chronically active to intermittent or rare flares. Multiple genetic and environmental factors are known to contribute to the pathogenesis of IBD, including more than 230 loci for the disease that have been reported through GWAS analyses. Many of the genes residing at these loci have been implicated in pathways related to the immune system and the microbiome.

However, there is also increasing evidence for a clinical association of IBD with stress and depression. Given the role of the hypothalamus in stress responses and in the pathogenesis of depression, the researchers decided to explore the genetic role of the hypothalamus in IBD.

To begin, the researchers performed genetic correlation analyses between IBD and depression to assess the degree of genetic commonality between the two conditions, using publicly available data. The research team used depression as a proxy for stress because there are a limited number of GWAS efforts focused on a consistent definition of stress, while in contrast, the genetics of depression has been relatively well-studied, resulting in a large, relatively uniform body of work.

Analyzing eleven autoimmune diseases for correlations with depression, the researchers found IBD was the most statistically significantly trait positively correlated with depression, though asthma and multiple sclerosis were noted as being highly correlated as well.

The research team then performed further analyses in order to validate the correlation between IBD and depression. First, they measured the enrichment of IBD-associated genetic variants in the 3D genomic patterns within hypothalamic-like neurons (HNs) and colonoids from rectal biopsies and found a highly significant four-fold increase in HNs and a seven-fold increase in the better-known colonoid setting. The researchers then used a sophisticated "variant-to-gene mapping" approach devised at CHOP to determine which genes are implicated in the pathogenesis of IBD at these enriched signals. Then, assessing those implicated genes, the researchers looked for pathways potentially influenced by IBD-associated genetic variants.

Through this variant-to-gene mapping effort, the researchers implicated 25 genes in HNs for conferring risk for IBD. Eleven of those genes have known functions in the brain, in particular CREM, CNTF and RHOA, which are genes that encode key regulators of stress. Seven of those genes were also implicated in the colonoids. In terms of pathways, the researchers observed an overall enrichment for hormonal signaling pathways, in addition to the expected enrichment in immune and microbiome signaling pathways.

"We propose that some IBD-associated variants alter the hypothalamus-pituitary-adrenal axis and stress responses, which could in turn play a role in predisposing patients to this disease and exacerbating its presentation," Grant said. "Future studies are warranted to refine our understanding of the role of the hypothalamus in IBD onset."

Source:

Journal reference:

Lasconi, C., et al. (2020) Variant-to-gene-mapping analyses reveal a role for the hypothalamus in genetic susceptibility to inflammatory bowel disease. Cellular and Molecular Gastroenterology and Hepatology. doi.org/10.1016/j.jcmgh.2020.10.004.

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Study suggests a role for the hypothalamus in genetic susceptibility to IBD - News-Medical.Net

Genetics

Prowess of Bionano Genomics’ Saphyr System in Uncovering Novel Genetic Variations That Cause Cancer and Genetic Disease in Full Display at ASHG 2020 -…

SAN DIEGO, Oct. 27, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced that human genetics researchers using the Saphyr system will present their results at the American Society of Human Genetics (ASHG) Annual Meeting, being held virtually at http://www.ashg.org between October 27-30. The impact of structural variation analysis using the Saphyr system will be demonstrated at ASHG with 18 oral and poster presentations which cover an expanding array of diseases like cancer predisposition, microdeletion syndromes, repeat expansion disorders, neurodegenerative diseases, disorders of sex development and a variety of other genetic diseases. Additionally, these presentations show Saphyrs abilities to elucidate the exact structure of complex genomic rearrangements such as large inversions, chromothripsis and low copy repeats.

The scientific importance and quality of the studies utilizing Saphyr and presented at ASHG have increased year over year, said Erik Holmlin, Ph.D., CEO of Bionano. As more scientists present and publish their important discoveries made with Saphyr, an increasing number of potential future Saphyr users become aware of its prowess in uncovering novel genetic variants that contribute to cancer and genetic disease, which could drive more adoption and utilization for basic genetic research and clinical studies alike.

Below is a summary of key presentations to be given at ASHG 2020 featuring the use of Bionanos optical genome mapping technology:

Live Presentation October 29, 2020, 11:45AM-12:00PMDeciphering Genomic InversionsChristopher M. Grochowski, Baylor College of MedicineGenomic inversions are a class of structural variation (SV) relevant in evolution, speciation, and human disease but challenging to detect and resolve using current genomic assays. While short-read WGS can detect a fraction of copy number neutral inversions, those mediated by repeats or accompanied by CNVs remain challenging. The utilization of multiple technologies and visualization of unbroken DNA through long molecule approaches facilitate detection ofin cisevents and resolution of SVs containing two or more breakpoint junctions.

The following Co-Labs, Poster Sessions and Abstracts are available for on-demand viewing during and after ASHG 2020:

Bionano Laboratory Co-Lab Session: Resolving Complex Haplotypes Implicated in Alzheimers and Other Neurodegenerative Diseases.Mark T. W. Ebbert, Neuroscience Department, Mayo ClinicAlzheimers disease is genetically complex with no meaningful therapies or pre-symptomatic disease diagnostics. Most of the genes implicated in Alzheimers disease do not have a known functional mutation, meaning there are no known molecular mechanisms to help understand disease etiology.

In this co-lab session, Mark T. W. Ebbert of the Mayo Clinic will discuss his teams work toward identifying functional structural mutations that drive disease in order to facilitate a meaningful therapy and pre-symptomatic disease diagnostic. Some of the genes and regions implicated in Alzheimers disease are genomically complex and cannot be resolved with short-read sequencing technologies. These regions include MAPT, CR1, and the histocompatibility complex (including the HLA genes).

3342 Bionano Poster Session: High Throughput Analysis of Disease Repeat Expansions and Contractions by Optical MappingErnest Lam, Sr Manager Bioinformatics, Bionano GenomicsRepeat expansions and contractions are associated with degenerative disorders such as facioscapulohumeral muscular dystrophy (FSHD). Southern Blotting is the gold standard for long repeat analysis but has many limitations. Optical genome mapping allows for efficient analysis of diseases associated with repeat expansion and contraction.

2190 Bionano Poster Session: Rapid Automated large Structural Variation Detection in Mouse Genome by Whole Genome SequencingJill Lai, Sr Applications Scientist, Bionano GenomicsIdentifying SVs for key model organisms such as mouse and rat is essential for genome interpretation and disease studies but has been historically difficult due to limitations inherent to available genome technologies. We updated the Saphyr analysis pipeline such that copy number variant (CNV) and SV analyses could now be applied to mouse and other non-human species, and constructed a control SV database for annotating variants, and identified strain-specific SVs/CNVs as well as variation shared among strains.

Additional presentations/abstracts featuring optical genome mapping:

3208 - Long-read sequencing and optical mapping decipher structural composition ofATXN10repeat in kindred with spinocerebellar ataxia and Parkinsons diseasePresented by Birgitt Schuele, Associate Professor, Department of Pathology, Stanford University School of Medicine

3270 - Uniparental isodisomy, structural and noncoding variants involved in inherited retinal degeneration (IRD) in three pedigreesPresented by Pooja Biswas, Ophthalmology Department, University of California, San Diego

Data CoLab: Whole Genome Map Assembly and Structural Variation Analysis with Hitachi Human Chromosome ExplorerPresented by Hitachi-High-Tech America, Inc.

2123 - High-throughput sequencing and mapping technologies applied to 10 human genomes with chromothripsis-like rearrangementsPresented by Uir Souto Melo, Mundlos Lab, Max Planck Institute for Molecular Genetics, Berlin, Germany

2165 -nanotatoR: A tool for enhanced annotation of genomic structural variantsPresented by Emmanuele Delot, Center for Genetic Medicine Research, Childrens National Hospital, Washington, DC

2998 - Highly variable structure and organization of the human 3q29 subtelomeric segmental duplicationsPresented by Umamaheswaran Gurusamy, Cardiovascular Research Institute, University of California San Francisco

2304 - Enlightening the dark matter of the genome: Whole genome imaging identifies a germline retrotransposon insertion inSMARCB1in two siblings with atypical teratoid rhabdoid tumorPresented by Mariangela Sabatella, Princess Mxima Center for Pediatric Oncology, Utrecht, Netherlands

2318 - FaNDOM: Fast Nested Distance-based seeding of Optical MapsPresented by Siavash Raeisi Dehkordi, Computer Science & Engineering, University of California San Diego, La Jolla

3023 - Structural hypervariability of low copy repeats on chromosome 22 is human specificPresented by Lisanne Vervoort, Department of Human Genetics, KU Leuven, Leuven, Belgium

3024 - Telomere-to-telomere assembly and complete comparative sequence analysis of the human chromosome 8 centromereReviewer's Choice Award RecipientPresented by Glennis Logsdon, Genome Sciences, University of Washington, Seattle, WA

3311 - Comprehensive structural variant identification with optical genome mapping and short-read sequencing for diagnosis of disorders/differences of sex development (DSD)Reviewer's Choice Award RecipientPresented by Hayk Barseghyan, Center for Genetic Medicine Research, Children's National Hospital, Washington, DC

3318 - De novo mutation and skewed X-inactivation in girl with BCAP31-related syndromePresented by H.J. Kao, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

3560 - Resolving genomic structures inMECP2Duplication Syndrome provides insight into genotype-phenotype correlationsReviewer's Choice Award RecipientPresented by Davut Pehlivan, Molecular and Human Genetics, Baylor College of Medicine, Houston, TX

2157 -methometR: quantification of long-range haplotype specific methylation levels from Optical Genome MapsPresented by Surajit Bhattacharya, Center for Genetic Medicine Research, Childrens Research Institute, Childrens National Hospital, Washington, DC

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visitwww.bionanogenomics.com or http://www.lineagen.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the timing and content of the presentations identified in this press release; the effectiveness and utility of Bionanos technology in basic genetic research and clinical settings; the contribution of Saphyr to uncovering novel genetic variants that contribute to cancer and genetic disease; the benefits of Bionanos optical mapping technology and its ability to facilitate genomic analysis in future studies; and Bionanos strategic plans. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, PhDLifeSci Communications+1 (617) 733-7668darren@lifescicomms.com

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Prowess of Bionano Genomics' Saphyr System in Uncovering Novel Genetic Variations That Cause Cancer and Genetic Disease in Full Display at ASHG 2020 -...