Category Archives: Human Genetics

NEW YORK De novo mutations affecting more than two dozen candidate genes appear to contribute to forms of male infertility caused by very low sperm counts or absence of sperm, according to new research presented this week at the American Society of Human Genetics annual meeting, held virtually this year.

For their study, investigators in the UK, the Netherlands, Australia, Germany, and elsewhere sequenced the exomes of 185 men with unexplained forms of severe oligozoospermia (far lower-than-usual sperm counts) or azoospermia (sperm-free ejaculate), comparing their protein-coding sequences to those of their unaffected parents. They also tapped into data for participants from the International Male Infertility Genomics Consortium.

"Traditionally, male infertility has been investigated under a recessive model of inheritance, but following this method, a large proportion of cases remain unexplained," Miguel Xavier, a postdoctoral research associate at the Newcastle University Biosciences Institute, noted during a poster preview presentation at the conference on Monday.

With that in mind, the team searched for de novo mutations in the infertile male participants that had not been inherited from either unaffected parent, reasoning that infertility and conditions with related symptoms such as Klinefelter syndrome have previously been linked to chromosome-level de novo alterations.

In the process, the investigators flagged 192 rare de novo mutations in the affected men a set that they subsequently whittled down to 29 candidate mutations based on predicted mutation severity and functional effects.

These included 21 missense mutations, four frameshift changes, a handful of in-frame insertions or deletions, and one premature stop mutation, Xavier reported, noting that suspicious de novo mutations were overrepresented in RBM5 and other genes from messenger RNA maturation or splicing pathways that are typically expressed in the testes during sperm production.

"No other genetic abnormalities were found in these patients, which seems to indicate that the de novo mutations are the genetic cause for the infertility of these men," he added, noting that these mutations appear to exert a dominant effect on infertility.

In an abstract accompanying the presentation, he and his co-authors noted that RBM5 mutations were significantly more common in another group of more than 2,500 infertility cases than in a group of nearly 5,800 fertile male controls. The team also saw higher-than-anticipated representation of de novo mutations in genes that are considered loss-of-function intolerant and in genes coding for interaction-heavy proteins.

Xavier cautioned that additional research is needed to tally the potential de novo contributors to infertility in larger participant groups from different populations, and to validate candidate genes uncovered so far. Even so, he said, results so far point to the possibility of identifying infertility culprits, or diagnosing patients, with the help of exome or genome sequencing.

"By expanding our knowledge of the causes of male infertility, we can not only provide a concrete answer to the individuals affected, but also help clinicians to better advise these patients on the best course of action to take in order to conceive," Xavier said in a statement, adding that "we hope that in the near future we are able to identify more genetic causes of infertility and start developing the means to overcome infertility in these patients. But first, we need to better understand the basics of sperm development and the genetic factors that disrupt it."

The team has provided additional details on the work in a paper under review at a scientific journal, and in a BioRxiv preprint out in February.

The study backs up similar results by others. In a pilot study published online in the journal Andrologyin September 2020, an independent team from Slovenia, Macedonia, and Serbia described de novo mutations found by sequencing more than a dozen parent-child trios involving patients with idiopathic azoospermia and another 16 singleton males with the condition.

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De Novo Mutations Linked to Male Infertility in Trio Exome Sequencing Study - GenomeWeb

SEATTLE--(BUSINESS WIRE)--Phase Genomics, Inc., a biotech company leading advancements in next-generation sequencing (NGS) solutions for genome assembly and analysis, today announced the launch of the beta version of its new platform for next generation cytogenomic applications in the reproductive genetics and oncology spaces.

The platform enables rapid, efficient sample processing and does not require culturing of live, dividing cells nor high-molecular-weight DNA extraction. This is a fast and inexpensive platform that is capable of providing tremendous benefit towards answering complex genomic questions that existing methods are unable to fully resolve,'' said Shawn Sullivan, Co-founder and CTO of Phase Genomics. The flexibility of this method allows us to use a low starting volume of cells from fresh and frozen material and, most notably, paraffin-embedded tissue. We can deliver an invaluable compendium of genetic information from a single sample without having to wait for results from multiple tests. With our robust chemistry and the machine learning underpinnings of our analytic technology, our platform offers the potential to complement or replace incumbent technologies like cytogenetics, FISH, and CMA in both solid and liquid cancers and in reproductive health.

While the platform can be broadly applied to constitutional genetics, Phase Genomics sees the immediate utility that it can bring to the prenatal market. According to Sullivan, the platform can help provide answers to the study of patient populations faced with infertility or unexplained repeated pregnancy loss. For example, our platform can detect cryptic rearrangements potentially causing a couples fertility issues, it can uncover novel structural and copy-number changes essential to fetal development in non-viable or paraffin-embedded POC tissue samples and, most importantly, help fuel the translation of these discoveries into clinical tools that will remove emotional, financial and other burdens borne by patients working through these heartbreaking conditions.

Many of the same challenges exist in oncology. Unlocking and maximizing the use of the genetic information contained in unculturable and paraffin-embedded cancer samples is a unique property of the Phase Genomics platform. Phase Genomics Co-founder and CEO Dr. Ivan Liachko stated, The Phase Genomics ultra-long-range sequencing method and machine learning-enabled analytical platform arm clinical researchers, and eventually, healthcare providers, with a cost-effective, high-throughput, sequencing-based method that delivers actionable information. This information provides insights that can be used in the development of new diagnostic and treatment options for cancer and genetic disease, ultimately leading to improved patient care and outcomes.

Todays announcement opens RUO platform access to early beta participants. Phase Genomics is engaged in a number of active partnerships with research and commercial entities and is presenting early results in a poster at the American Society of Human Genetics Conference. The Phase Genomics platform is for research use only and is not for use in diagnostic procedures. More information on the platform is available here.

Join Phase Genomics for a webinar on Tuesday, November 30th to learn more about this technology and follow Phase Genomics on Twitter for the latest news and information.

ABOUT PHASE GENOMICS

Phase Genomics applies Hi-C and other proximity-ligation methods to enable chromosome-scale genome assembly, metagenomic deconvolution, as well as analysis of structural genomic variation and genome architecture. They offer a comprehensive portfolio of laboratory and computational services and products, including Hi-C kits for plants, animals, microbes, and human samples as well as industry-leading genome and metagenome assembly and analysis software.

Based in Seattle, WA, the company was founded in 2015 by a team of genome scientists, software engineers, and entrepreneurs. The companys mission is to empower scientists with genomic tools that accelerate breakthrough discoveries.

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Phase Genomics Announces Next Generation Cytogenomics Platform to Advance Precision Diagnosis and Treatment in Reproductive Genetics and Oncology -...

West African migrations. Credit: The graph is made by Saoni Banerji, and the map was downloaded from Wikimedia

Researchers from Estonia and Italy developed an innovative method by combining neural networks and statistics. Using this newly developed method, they refined the Out of Africa scenario. The researchers claimed that the African dynamics around the time of the Out of Africa expansion are more complex than previously thought.

Archaeologists and geneticists agree that all modern humans originated somewhere in Africa around 300 thousand years ago. The population movement that colonized the rest of the globe occurred approximately 60-70 thousand years ago. Both Y-chromosomal data (which follows patrilineal lineage) and the Mitochondrial genome (which follows the matrilineal line) agree on this. However, the exact relationship between the people who left Africa and the human populations currently inhabiting the continent is not fully understood.

A simplistic model would see the first phase of within-Africa population subdivisions, followed by a separation between the ancestors of modern Eurasians and the ancestors of modern East or North-East Africans. New research on this topic, recently published in the American Journal of Human Genetics, argues that the Out of Africa expansion was preceded by a significant population turnover from East to West Africa. This event likely homogenized West and East Africans. This turnover, which may account for up to 90% of the contemporary West African gene pool, increased the affinity between West Africans and Eurasians. This event better explains the lower bound (~60 thousand years ago) inferred from genetic data for the separation time between Africans and non-Africans.

A similar hypothesis was proposed before for the Y chromosome. But this is the first time we demonstrated it for autosomal DNA, said Francesco Montinaro, a Lead author in this study from the University of Bari. Autosomal DNA comes from both parents, instead of Y-chromosome or Mitochondria, which comes only from one of our parents.

It is fascinating to see how our understanding of the human past becomes ever more complex and detailed. Our new model can give us a clue why West Africa shows such a young separation time from the out of Africa populations, said Vasili Pankratov, a lead co-author from the University of Tartu.

Reference: Revisiting the out of Africa event with a deep-learning approach by Francesco Montinaro, Vasili Pankratov, Burak Yelmen, Luca Pagani and Mayukh Mondal, 8 October 2021, American Journal of Human Genetics.DOI: 10.1016/j.ajhg.2021.09.006

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Revisiting the Out of Africa Theory: New Narrative From Genetic Analysis and AI - SciTechDaily

By Lee Lawler Oct 15, 2021

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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

Jomon teeth vs Native American teeth. Credit: G. Richard Scott, University of Nevada Reno

Latest scientific findings suggest the ancestral Native American population does not originate in Japan, as believed by many archaeologists.

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 on October 12, 2021, 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 analyzed 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 nor the genetics indicate a connection between Japan and 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.

Reference: Peopling the Americas: Not Out of Japan' by G. Richard Scott, Dennis H. ORourke, Jennifer A. Raff, Justin C. Tackney, Leslea J. Hlusko, Scott A. Elias, Lauriane Bourgeon, Olga Potapova, Elena Pavlova, Vladimir Pitulko and John F. Hoffecker, 12 October 2021, PaleoAmerica.DOI: 10.1080/20555563.2021.1940440

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Genetics and Skeletal Biology Debunks Popular Theory of Native American Origins - SciTechDaily

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

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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

iNDICA NEWS BUREAU-

The American Association of Physicians of Indian Origin (AAPI), the largest ethnic medical organization in the United State, recently organized a special event to bring awareness to the rising cases of cardiovascular diseases among the South Asian diaspora.

South Asians make up 25 percent of the worlds population but they contribute 50 percent to global cardiovascular deaths.

The event was conducted virtually on Saturday, October 16, and was presented by two eminent speakers and experts, Dr. Enas Enas and Dr. Amit Kera.

President of AAPI, Dr. Anupama Gotimukula, in her welcome speech, highlighted the growing epidemic heart diseases due to unhealthy lifestyle and called out for the need to create a global awareness.

Today is World Restart a Heart Day. Todays conference is being organized to educate and create awareness about the major health issue faced by South Asians and offer ways to mitigate heart disease, Dr. Gotimukula said.

Dr. Enas came forward to give a deeper insight on the History and Magnitude of Heart Disease Among South Asians.

He pointed out that 185,000 people of South Asian origin die of heart disease per year as against 15,000 Whites die of the same health issue. He specifically noted that Indians have a big problem with premature heart disease.

Dr. Enas, is a reputable cardiologist from Chicago and also Director of CADI Coronary artery disease in Indians

He is the first cardiologist to sound the alarm on the strikingly high rates and malignant nature of heart disease among Indians in the US and around the globe. He is also the first physician to identify and report a genetic predisposition to CAD in Asian Indians, mediated through lipoprotein(a) a genetic variant of LDL cholesterol.

Dr. Amit Kera, a new rising star in Preventive Cardiology, built on that argument and presented genomic data to fill the gap. He is a physician-scientist with expertise in epidemiology, clinical medicine, and human genetics.

Dr. Kera He advocated for the need for our own data base and especially genomic data to go beyond coronary calcium score and use Polygenic score, which can predict even more accurately the risk of heart disease individually what he calls Precision Medicine.

Dr. Brahma Sharma, Senior Faculty at the University of Pittsburgh affiliated Medical Center, a co-host and moderator of the event, said, While we are still trying to figure out different mechanisms for this enigma, that should not prevent but rather motivate to follow more aggressively life style modifications and pre-empt and prevent this silent epidemic that is taking a toll on young Indians and South Asians globally.

Dr. Sharma, serves as the Chair of AAPI South Asian Heart Disease Committee and as the Chair AHA/ AAPI Liaison.

As the adage goes, Prevention is better than cure, said Dr. Gotimukula in her closing remarks. She urged her fellow doctors and contemporaries to raise the awareness to the highest level and create a community that foster healthy lifestyle.

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AAPI keen on creating awareness on the rising cases of heart disease among South Asians - indica News

ATLANTA, Oct. 6, 2021 /PRNewswire/ --JScreen, http://www.jscreen.orga national public health initiative based out of Emory University School of Medicine's Department of Human Genetics, adds yet another way to save lives with the successful hard launch of its CancerGEN testing initiative. This new JScreen initiative offers at-home testing for more than 60 cancer susceptibility genes associated with hereditary risks for breast, ovarian, prostate, colorectal, skin and many other cancers.

During the Pandemic we have all learned how critical it is to take healthcare into your own hands. With October Breast Cancer Awareness Month and Prostate and Ovarian Cancer Awareness months in the fall, and the staggering statistics showing that half of all men and a third of all women will develop cancer during their lifetime, JScreen understands the importance of giving people a heads up if they have a hereditary risk for cancer. This not-for-profit home education and genetic screeningprogramstarted in 2013 with reproductive genetic testing called ReproGEN, and now tests for risk for over 40 types of hereditary cancer with the addition of the CancerGEN test.

"Making cancer genetic testing accessible is key," said Jane Lowe Meisel, MD, Associate Professor of Hematology and Medical Oncology at Emory University School of Medicine, and medical director for JScreen's cancer program."This type of testing is important because it alerts people to their risks before they get cancer. They can then take action to help prevent cancer altogether or to detect it at an early, treatable stage."

Getting tested through JScreen is easy. All you have to do to receive your simple at-home test is sign up online, provide a saliva sample and use pre-paid postage to mail it in, making JScreen.org pandemic proof since before the pandemic! JScreen's tests use state-of-the-art genetic sequencing technology to ensure highly accurate results. The robust cancer testing panel includes genes that are actionable, meaning there is something that can be done to help prevent cancer if a person tests positive.JScreenprovides risk information in the record-breaking time of three weeks or less. Importantly, licensed genetic counselors provide consults via phone or secure video conferencing to ensure that people understand their results.

One of JScreen's goals is to make testing affordable. ReproGEN currently costs $149 and CancerGEN is $199. JScreen also offers need-based financial assistance.

The proof of JScreen's passion for saving lives is in the incredible stories they hear, the healthy babies that are born and the people that can now take action to avoid a cancer diagnosis. As the JScreen team likes to say "we are a small team with a huge footprint."

"Knowledge is power.With an understanding and awareness of their cancer risks and available options, individuals can work with their health-care providers on next steps," said Karen Arnovitz Grinzaid, MS, CGC, Assistant Professor of Human Genetics at Emory University School of Medicine, and JScreen's Executive Director."Launching our new cancer program and providing convenient and affordable access to cancer genetic testing across the US will help save lives."

About JScreen

JScreenis a national non-profit public health initiative dedicated to preventing genetic diseases and cancer.Headquartered in Atlanta at Emory University School of Medicine, the JScreen initiative provides convenient at-home access to cutting-edge genetic testing technology, patient education and genetic counseling services. JScreen believes the combination of education, access to premier genetic screening technologies and personalized, confidential support are the keys to preventing devastating diseases.

Media contact:

Hayden Ari

320734@email4pr.com

973-405-4600

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JScreen.org Adds CancerGEN to National Genetic Screening Program Just in Time for Cancer Awareness Months This Fall - Johnson City Press...

The first look at a threatened rattlesnake species recent genetic history suggests that inbreeding necessitated by limited habitat may not be as detrimental as theory would predict it to be.

In fact, scientists speculate that Eastern massasauga rattlesnakes may have pre-adapted to living in small, isolated populations where the most dangerous genetic mutations that arose could be easily exposed and purged.

Researchers sequenced the genomes of 90 Eastern massasauga rattlesnakes, which were listed as threatened under the Endangered Species Act in 2016 because of loss and fragmentation of their wetland habitat. For comparison, the researchers also sequenced 10 genomes of a close relative, the Western massasauga rattlesnake, a common species with no limitations on breeding opportunities and large populations.

The Ohio State University team found that the most potentially damaging gene mutations were less abundant in the Eastern than the Western species. This finding suggests the breeding limitations of small, isolated populations might be accompanied by an evolutionary advantage of being able to elbow out genetic variants that get in the way of survival, saidH. Lisle Gibbs, professor of evolution, ecology and organismal biology at Ohio State and senior author of the study.

This is something that has been reported very recently in other endangered species, but its the first time its been shown in a reptile, Gibbs said. We always worry about genetics and the loss of variation and what it means to be in a small population in which theres lots of inbreeding. At least in this species, maybe its not such a big deal.

From a conservation perspective, perhaps we can downplay genetics and say ecology such as habitat restoration is more important.

Gibbs completed the study with Alexander Ochoa, a former postdoctoral researcher at Ohio State who is now a postdoctoral scholar at the University of Central Florida. The research is published in the journal Molecular Ecology.

Eastern massasauga rattlesnakes live in isolated spaces in midwestern and eastern North America, and evolutionary theory posits that the inevitable inbreeding in such populations threatens species with extinction as genetic mutations accumulate. The smallest populations might reach 30 snakes, but Ohios Killdeer Plains Wildlife Area is home to one of the most genetically diverse and largest populations in the country, numbering in the thousands.

Gibbs has studied Eastern massasaugas for over two decades and, as director of the Ohio Biodiversity Conservation Partnership, advises the Ohio Department of Natural Resources on management of the species.

Through years and years of study, we know that most populations are isolated, like little natural zoos scattered throughout the landscape, Gibbs said. Due to habitat degradation, weve known they show little variation but weve never actually looked at variation in genes that code for things that matter to a rattlesnake.

Only recently has it been possible to apply the research techniques perfected with the human genome to work with this species. Gibbs and Ochoa zeroed in on identifying mutations in genes that may affect survival and reproduction to gauge how hazardous inbreeding might be to Eastern massasaugas.

Though a higher overall number of potentially deleterious mutations were found in the common Western massasaugas, that didnt translate to more threats to their survival because most troublesome gene copies were offset by protective copies. That can happen only in heterozygotes, which have two different copies, or alleles, of a particular gene one inherited from each parent. Because of generations of inbreeding, Eastern massasaugas are much more likely to have two copies of the same allele.

Thats why inbreeding has impacts because thats when you get two bad alleles showing up together, with no good allele to compensate, so there is a negative effect, Gibbs said. Theres more inbreeding, so overall you get more mostly bad mutations together, but the really bad ones, because theyre exposed, are also eliminated at a much greater rate.

Through another analytical technique comparing the narrowing of the Eastern and Western massasauga genetic makeup over several hundred years, Gibbs and Ochoa confirmed the impact human activity has had on the Eastern massasaugas swampy habitat. Unlike the Eastern species, Western massasaugas live in grassy and woodland regions of the south-central United States that are less densely populated by humans.

We looked at what has happened in these snakes and their population sizes over the last 300 years, which is when humans have been tromping all over North America, impacting the landscape, Gibbs said. The impacts in terms of reducing population sizes are greater in Eastern than in Western massasaugas over this period.

The findings could influence management decisions. A common conservation practice would involve introducing snakes from a more genetically diverse population into a highly isolated group to counter the effects of inbreeding. But it turns out the Eastern massasauga might benefit more from preservation of its habitat while the genetics takes care of itself.

This counterintuitive result makes us rethink what living in a small population is, and whether genetic problems are as important as we think they are, Gibbs said. This is certainly not to say living in a small population isnt bad it just may be that the genetic effects are not as bad as we thought.

This work was supported by the State Wildlife Grants Program administered jointly by the U.S. Fish and Wildlife Service and the Ohio Division of Wildlife, with funds provided by the Ohio Biodiversity Conservation Partnership between Ohio State and the Ohio Division of Wildlife, as well as the National Science Foundation.

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Threatened rattlesnakes' inbreeding makes species more resistant to bad mutations - The Ohio State University News

Article In Brief

Experts in movement disorders highlighted advances in the field from 20 years ago to now, including improvements in deep brain stimulation, earlier treatment with levodopa, and a focus on nonmotor symptoms.

While neurologists still hope for elusive cures for movement disorders, they appreciate the major scientific advances that have led to a greater understanding and management of Parkinson's disease (PD), dystonia, and essential tremor.

Deep brain stimulation (DBS) is a major case in point. When DBS first received approval from the Food and Drug Administration in 1997, it was indicated for stimulating the ventral intermediate nucleus of the thalamus to treat tremor resulting from PD or essential tremor. In 2002, the FDA approved DBS of the subthalamic nucleus or internal portion of the globus pallidus internus to treat PD symptoms that were no longer adequately controlled with medications. The following year, DBS was approved for dystonia.

As a result, many clinicians and patients held it out as a last resort, said David Charles, MD, FAAN, a DBS researcher who is professor and vice chair of neurology at Vanderbilt University Medical Center in Nashville.

Then a European study became the catalyst for a paradigm shift in the United States when the FDA approved DBS in 2016 for mid-stage PD. The approval paved the way for the use of DBS as adjunct therapy when disease duration is at least four years and motor complications persist for four months or longer. Dr. Charles hailed that development as one of the biggest advances in DBS.

A number of studies have demonstrated that DBS often continues to be effective over the long haul. The data are very clear that DBS plus medicine is superior to medicine alone in controlling symptoms and improving quality of life in mid- and advanced-stage disease, he said. Furthermore, providing the therapy in mid-stage means that the person with Parkinson's gets many years of benefit.

DBS implantation techniques have become more targeted, greatly reducing the incidence of complications. It's actually safer to do the operation on people with mid-stage disease, because they are often younger and have fewer comorbidities, Dr. Charles said, explaining that the older the patient is, the higher the risk of an adverse event occurring.

The selection of DBS equipment also has expanded. Initially, only one manufacturer produced equipment approved for use in the United States, he said. Now, three companies are vying for market share.

The technology has also improved from the standpoint that electrodes, or leads, implanted in a patient's brain will now allow the physician to steer the current, Dr. Charles told Neurology Today. By directing the energy more precisely toward the optimal location in the brain, the physician can decrease the possibility of side effects. In addition, one of the devices can be programmed and adjusted remotely via telehealth.

While DBS remains an invasive procedure and the risks are never nil, it can be extremely effective, said Michele Tagliati, MD, FAAN, professor and vice chairman of neurology and director of the movement disorders division at Cedars-Sinai Medical Center in Los Angeles.

Dr. Tagliati noted that the last 20 years have seen the explosion, for lack of a better term, of deep brain stimulation for movement disorders. FDA approval for PD came again in 2002 and in 2003 for dystonia, following the approval for essential tremor in 1997.

With properly selected patients and in good handsin terms of surgery and programming the deviceDBS can be life-changing in advanced Parkinson's, untreatable dystonia, and medication-refractory essential tremor, he said, adding that the incidence of complications is much lower under a seasoned surgeon's wing.

Recent progress in human genetics also has led to significant strides in the understanding of PD and related disorders. For instance, in the last two decades, scientists have discovered many more contributing genes. Mutations in the glucocerebrosidase gene, which encodes the lysosomal enzyme that is impaired in Gaucher's disease, are relatively common risk factors for movement disorders.

Although genetic cause is thought to be a small proportion of Parkinson's, this is an important discovery for therapeutics, said Cheryl H. Waters, MD, FAAN, FRCPC, the Albert and Judith Glickman Professor of Neurology in the division of movement disorders at Columbia University Medical Center in New York. Identifying the genes helps establish new drug targets that may help some, if not, all patients.

During this time framein the early 2000sanother discovery led to an association between PD and mutations in the leucine-rich repeat kinase-2 gene.

One of the big changes in the last 20 years, from my perspective, is the recognition of genetic mutations that can increase risk of Parkinson's, said Andrew S. Feigin, MD, professor of neurology at NYU Langone Health and director of the Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders.

This holds a lot of promise, Dr. Feigin said. Future clinical trials will likely target therapies at mechanisms related to these genetic mutations.

More recently, deep phenotypingthe use of big data to arrive at full clinical and biomarker characterizationis a strategy that has the potential to change the prognostic landscape for movement disorders, said Christopher G. Goetz, MD, FAAN, professor of neurological sciences and pharmacology at Rush University Medical Center in Chicago.

To this end, neurologists are playing a pivotal role in the epidemiological research arena by collecting repositories on patients, documenting behaviors such as hallucinations and dyskinesias, duration of their PD since onset, and the presence or absence of a genetic link to their disorder. The repositories could be useful to compare patients with similar profiles miles apart, even in different countries, said Dr. Goetz, a senior neurologist in the movement disorders program at Rush.

In the past, when we were trying to understand how a patient would respond or have a prognosis, we looked at the meanthe averageresponse across the population, and now we are thinking that's not the strategy, he said. Instead, we should be phenotypingdeeply understanding each patient's profile.

The idea that we could learn from all the big data of an individual essentially represents a whole new way of thinking, Dr. Goetz added. In advancing this notion a step further, he suggested that theoretically, we could predict also who would respond better to a given medication. It's a new concept that we didn't have 20 years ago.

On the medication front, neurologists have come to a consensus that they should consider prescribing levodopa sooner rather than later. There has been a significant change in Parkinson's disease management, with the pendulum swinging towards more use of levodopa and less use of dopamine agonists, even early in the disease, said Melissa J. Nirenberg, MD, PhD, FAAN, professor of neurology at the Icahn School of Medicine at Mount Sinai in New York.

We have learned that dopamine agonists can cause impulse control disorders, Dr. Nirenberg added, noting that some patients may develop severe withdrawal symptoms. Known as dopamine agonist withdrawal syndrome, this complication can make it difficult to taper treatment.

Neurologists previously were reluctant to use levodopa early in PD due to unfounded fears that it might be toxic to the brain or worsen long-term outcomes. It is now clear that levodopa is not neurotoxic and does not worsen outcomes, said Dr. Nirenberg, a member of Neurology Today's editorial board. Levodopa is the most effective treatment for Parkinson's disease, and it should be used as needed to treat symptoms.

Dr. Waters agreed with that assessment, stating that whereas 20 years ago we might have used dopamine agonists, we now recognize a high risk of impulsive and compulsive behaviors with dopamine agonists, she said. So, we do not delay levodopa, as it was shown not to cause the disease to progress more rapidly or lose its efficacy over time.

Many adjunctive agents, such as infusion and rescue therapy, have been helpful as complements to levodopa therapy. Rescue therapies, which can reduce the burden of the off experience for patients, include injections of apomorphine, sublingual apomorphine, and inhaled levodopa, she added.

Dr. Waters pointed out, too, that there are now three vesicular monoamine transporter type 2 inhibitors for the treatment of tardive dyskinesia and possibly the tics associated with Tourette syndrome. Side effects include drug-induced or secondary parkinsonism and depression. Not all have been approved for these indications in the United States.

Another major change in our understanding and treatment of Parkinson's disease has been the increased recognition of nonmotor symptoms, Dr. Nirenberg said, citing the need to diagnose and treat these symptoms. This is a very active area of study and very important in the clinic, she said.

These concerning signs run the gamut from sleep disorders to cognitive decline, depression, urinary problems and constipation, as well as hallucinations, anxiety, depression, orthostatic hypotension, or a combination of such disturbances, neurologists noted.

Rapid eye movement sleep behavior disorder is one of the most indicative nonmotor manifestations of PD and can be particularly disruptive, Dr. Feigin said, because patients may end up punching their bed partner, falling on the floor, or even sleepwalking as they literally act out their dreams.

Neurologists interviewed for the article highlighted orthostatic hypotension as yet another nonmotor symptom of PD. However, they noted, more treatments are also more available for various nonmotor complications than there were 20 years ago, as is the case with the impact of depression on PD. This increasing awareness has led to better management of depression, including more frequent use of antidepressants, helping patients feel and function better, they said.

Neurologists also have become more adept at differentiating typical PD from atypical forms of the disorder, such as multiple system atrophy and progressive supranuclear palsy. Clinical characteristics complemented by magnetic resonance imaging can make a significant difference in these assessments, allowing clinicians to determine the treatment course, progression, and prognosis, Dr. Waters said.

Advancing technology has brought other benefits as well. Applications catering to remote office visits have been useful for monitoring patients and for engaging them in physical activities, particularly during the pandemic, she said, adding that the only thing that we've learned for certain to protect [against the progression of] Parkinson's is exercise.

Dr. Feigin concurred that there has been more widespread use of nonmedical interventions to improve the quality of life for patients with PD. Among the plethora of options are physical therapy, boxing programs, and dance and art initiatives. While they may not slow disease progression, these approaches have been helpful to people, he said. And there is some evidence that these types of therapies may improve long-term functioning and general well-being.

The importance of multifaceted care cannot be understated. In one day, Dr. Tagliati noted, patients with movement disorders can consult with several specialists under one rooffor instance, a neurologist, neurosurgeon, psychologist, and physical therapist. The convenience represents an evolution toward multidisciplinary care clinics in premier academic medical centers that serve as a one-stop shop for meeting patients' multiple needs.

Patients love this opportunity to share their different problems with different specialists in one single day, in one single morning, Dr. Tagliati said. That's one of the trends he has observed in his specialty when he compares it with two decades ago. The changes are particularly notable for PD, which he calls the bread and butter of movement disorders due to its frequency.

Training of neurology residents and fellowship trainees has adapted to these myriad changes. Residents are taught to identify various movement disorders, while fellows learn much more than previous cohorts of trainees, Dr. Waters said.

Fellows must recognize all the illnesses within the subspecialty, determine when to order genetic testing, and how to perform botulinum toxin injections and conduct DBS programming. They also need to be well-versed in all the different medications and know how to interpret imaging studies. In addition, she said, they may become involved in administering advanced treatments such as intestinal gel or subcutaneous infusions or rescue therapies.

Patients are also better educated and now seek input from neurologists at earlier stages of their disease trajectory than they did 20 years ago. This affords neurologists the opportunity to treat them with lower doses of medications, reducing the rate of side effects, said Dr. Goetz.

But at times, it is still disconcerting that curative treatments haven't emerged. Our disappointment is that we don't know precisely what causes Parkinson's, and multiple clinical trials for neuroprotection have failed, Dr. Waters said, adding that we have failed in finding treatments for freezing of gait, dementia, and fatigue.

Dr. Nirenberg remains enthusiastic about active clinical trials investigating drugs that specifically target genetic subtypes. She is also excited about the study of biomarkers, including blood, tissue, and spinal fluid markers and imaging studies that can facilitate early diagnosis and make a difference in bringing about breakthrough discoveries.

The holy grail is to find disease-modifying treatment for Parkinson's, she said. I hope that we will be able to offer patients such treatments way before the next anniversary issue [of Neurology Today]. That's what we're working on right now.

Dr. Goetz's contends that the inevitably progressive nature of neurodegenerative diseases doesn't mean the field of movement disorders isn't brimming with optimism. In addition to his interest in deep phenotyping, he said alpha-synuclein, which damages the dopamine cell, could be a target for antibody therapy in the future.

Especially in the context of the COVID era, we're excited about the prospects, he said. Could we develop a vaccine against the abnormal synuclein, just like the way we did with the vaccine against a virus?

Another scientific area of possibilities stems from research into gut bacteria and their impact on the brain, suggesting that dietary changes could have a positive effect on patients with movement disorders.

We all wish that we could have cracked the disease in these past 20 years and that we found the single chemical equation for the causation of the diseasethe very first chemical reaction that takes a normal dopamine cell and starts to make it into a pathologic cell, Dr. Goetz said. We have failed to crack that today, but that doesn't mean that we won't crack it tomorrow.

Until then, if you can change a patient's quality of life, you have changed him and his family, and that is an enormous scientific contribution.

Rush University Medical has received funding for research by Dr. Goetz from the NIH, Department of Defense, and Michael J. Fox Foundation. Dr. Goetz has received a faculty stipend from the International Parkinson and Movement Disorder Society; guest professorship honorarium provided by the University of Chicago and Illinois State Neurological Society, a volume editor stipend from Elsevier Publishers, and royalties from Elsevier and Wolters Kluwer. Dr. Waters received research support from Neuraly, Biogen, Roche, and Sanofi; consulting fees from Kyowa, Sunovion, and Acadia; and speakers' honoraria from Adamas, Amneal, Kyowa, Neurocrine, and Acorda. Dr. Feigin has received honorarium from Kyowa-Kirin. Dr. Charles has received education grants paid to Vanderbilt from Aeon, Abbott, AbbVie, Boston Scientific, Impax, Intec, Ipsen, Lundbeck, Medtronic, Merz, Novartis, Pharma Two B, Supernus. He has received consulting fees from Merz, Supernus, Alliance for Patient Access, Newronika, Revance, and is a nonpaid member of the data safety and monitoring board for the trial, STN DBS in PD Sleep Dysfunction.

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