Category Archives: Transhuman News

New genetic disorder named for Children's Hospital of Philadelphia ... Science Daily Three scientists at Children's Hospital of Philadelphia who identified and studied a genetic disease have been recognized by having their names attached to the ... and more »

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New genetic disorder named for Children's Hospital of Philadelphia ... - Science Daily

Identifying genes key to human memory: Insights from genetics and cognitive neuroscience Science Daily The study is among the first to identify correlations between gene data and brain activity during memory processing, providing a new window into human memory. It is part of the nascent but growing field of 'imaging genetics,' which aims to relate ... and more »

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Identifying genes key to human memory: Insights from genetics and cognitive neuroscience - Science Daily

An international team of researchers from institutions around the world, including Baylor College of Medicine, has discovered that mutations of the OTUD6B gene result in a spectrum of physical and intellectual deficits. This is the first time that this gene, whose functions are beginning to be explored, has been linked to a human disease. The study appears in the American Journal of Human Genetics.

Our interest in this gene began when we carried out whole exome sequencing the analysis of all the protein-coding genes of one of our patients who had not received a genetic diagnosis for his condition that includes a number of intellectual and physical disabilities, said co-first author Dr. Teresa Sim, a postdoctoral associate of molecular and human genetics and a fellow in Clinical Molecular Genetics and Genomics. We identified OTUD6B, a gene that until now had not been linked to a health condition.

We identified a presumed loss-of-function mutation in the OTUD6B gene in our first patient, said co-senior author Dr. Magdalena Walkiewicz, assistant professor of molecular and human genetics at Baylor and assistant laboratory director at Baylor Genetics. We discovered that this gene seemed to be highly involved in human development; when the gene cannot fulfill its function, the individual presents with severe intellectual disability, a brain that does not develop as expected and poor muscular tone that limits the ability to walk, as well as cardiovascular problems.

Making a convincing case for OTUD6B

However, one case does not represent sufficient evidence to support the involvement of OTUD6B in the medical condition.

To make a convincing case that this gene is essential for human development we needed to find more individuals carrying mutations in OTUD6B, Walkiewicz said.

Mutations in OTUD6B are rare so the researchers had to look into the exomes all the protein-coding genes of a large number of individuals to find others carrying mutations in this gene. Walkiewicz and her colleagues first looked into their clinical exome database at Baylor Genetics labs, specifically into the data of nearly 9,000 unrelated, mostly pediatric-age individuals, many of which carrying neurologic conditions, and found an additional individual carrying genetic changes in the same gene. The clinical characteristics of this individual were strikingly similar to those of the first patient, which led the team to expand their search for more patients.

When we study very rare disorders we rely on collaborations with scientists around the world to find other families affected by mutations in one gene, said Walkiewicz.

One of the strategies that helps researchers find more cases is running the gene of interest through GeneMatcher, a web-tool developed as part of the Baylor-Hopkins Center for Mendelian Genomics for rare disease researchers. Similar to online dating websites that match couples, GeneMatcher allows researchers to find others that are interested in the same genes they are working on.

Without this type of collaborations it would be very difficult to make a convincing case. Between GeneMatcher and our database we found a total of 12 individuals carrying mutations in OTUD6B and presenting with similar clinical characteristics, Walkiewicz said.

An animal model corroborates the human findings

Animal models are one way to determine whether a change in this gene is actually causing the condition, said co-senior author Dr. Jason Heaney, assistant professor of molecular and human genetics and director of the Mouse Embryonic Stem Cell Core at Baylor. Having a similar change in an animal model gene that results in similar characteristics in a mouse can show us whether the gene is causing the condition.

Baylor is part of the International Mouse Phenotyping Consortium. Its goal is to generate a knockout model for every gene in the mouse genome, about 20,000 protein-coding genes, and determine what each gene is involved with.

In this case we learned in the animal model lacking the OTUD6B gene that the gene is highly expressed in the brain and we knew that the patients had reduced intellectual capacities. The animals had cardiovascular defects very similar to those in the patient population. The animal models allowed us to see that having this mutation of this gene causes the clinical characteristics observed in the patients. It highlights how useful animal models can be for understanding human disease, Heaney said.

Through multiple lines of evidence the researchers have established that mutations in OTUD6B can cause a range of neurological and physical conditions and highlight the role of this gene in human development.

In addition, our collaborators in Germany performed functional analysis for this gene on blood cells from patients, Walkiewicz said. Their findings suggest that the OTUD6B protein contributes to the function of proteasomes, large molecular complexes that are at the center of the cellular process that degrades proteins that are damaged or are not needed by the cell. This discovery strengthens the notion that disturbances of the proteasome can cause human disease.

There is interest in better understanding the mechanisms of the disorder at the cellular and molecular level. By understanding the processes that lead to the disease, we can then hope to develop therapies for those patients, said Walkiewicz. One of the highlights of this project is the tremendous collaboration with a number of different centers and labs and putting this tremendous effort together resulted in a publication that is very strong.

Another important contribution of this project is that we provided some answers for the families, and brought them together which offers the opportunity of mutual support, said Sim.

This article has been republished frommaterialsprovided by Baylor College of Medicine. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Teresa Santiago-Sim, Lindsay C. Burrage, Frdric Ebstein, Mari J. Tokita, Marcus Miller et al. and Federico Zara. Biallelic Variants in OTUD6B Cause an Intellectual Disability Syndrome Associated with Seizures and Dysmorphic Features. The American Journal of Human Genetics, 2017; DOI: 10.1016/j.ajhg.2017.03.001

Link:
Gene Linked to Wide Range of Intellectual, Physical Disabilities - Technology Networks

Editors note: This commentary is by Steve May, who is a member of the Richmond Selectboard and a licensed independent clinical social worker. He has served previously as a national director of state Affairs for the Hemophilia Federation of America and is founder of The Forum on Genetic Equity, a national organization on genetic bias.

H.R.1313 (the Preserving Employee Wellness Programs Act) passed markup out of the House Ways and Means Committee on a party line vote with 22 Republicans voting for the bill and 17 Democrats voting against it. While the bill hasnt gotten anywhere near the attention the repeal of the Affordable Care Act has, overturning genetic privacy rules would have every bit as consequential an impact. H.R.1313 would permit genetic testing to be rolled into workplace wellness programs.

Obama era laws and regulations permitted for certain workplace wellness programs to be voluntary. The degree by which it would be voluntary going forward serves as something of an open question. There is a consensus amongst hiring managers and HR professionals that the only programs which are truly effective are the ones which target costly chronic and genetic conditions. Employers in targeting these would gain two significant pieces of information. Through enrollment and utilization they could target those who are healthy and identify those who have reason to believe they are not.

People with genetic conditions will either not be hired or hired at lower wages than they otherwise would have received as their employers and thus their insurers now know with less uncertainty future medical expense obligations.

These programs through coercive activity or incentive would create an opt-in and present little concern for those who are well. They would present their own genotype eagerly, demonstrating their own genetic wellbeing. Even a voluntary system shifts the onus onto those who for one reason or another chooses to not participate. Second, though opting out these employers would get genetic profiles with highly probable high cost diseases flagged. Far more dangerous to workers would be ones decision to not participate. While voluntary, these programs intend to compel individual participation by employers. If the cost of non-participation is high, that is a very valuable signal that the non-participating person has a damn good reason to not participate. And now they have demonstrated that they are not a team player which is really a proxy for a high likelihood of having a high probability of having a high cost genetically influenced condition. So people with genetic conditions will either not be hired or hired at lower wages than they otherwise would have received as their employers and thus their insurers now know with less uncertainty future medical expense obligations.

Following more than a decade of consultation, lobbying and advocacy, a Democratic Congress passed and a Republican president enthusiastically supported, championed and signed the Genetic Information Non-discrimination Act (GINA) in 2008. GINA is widely considered to have been the first major civil rights law of our new century; and it has successfully managed to safeguard the genetic privacy rights of every American every day for the last decade. The American Society for Human Genetics has come out against the passage of H.R.1313 because it would effectively repeal the fundamental genetic and health privacy protections in GINA and the Americans with Disabilities Act. Passage of H.R.1313 would permit workplace wellness programs to ask employees questions about genetic tests taken by themselves or their families, and to make inquiries about the medical history of employees, their spouses, their children, and other family members as employees. It is foreseeable that hiring and promotion decisions could depend on the results of genetic testing.

Under existing law, an employer may not ask a potential employee to take a genetic test as a condition of employment. That is to say they cannot pit two roughly equal applicants against one another and then consider the genetic factors and future affliction that might affect eventual employment. Supposing that you might be a carrier for BRCA-1, the genetic marker associated with breast cancer and another candidate may not, that single factor alone may be determinative in whether you get a job or a future promotion. It must be pointed out that simply being a carrier for a genetic condition does not mean that one necessarily will experience onset in most cases. In spite of that fact however, hiring managers can make employment decisions based on potential future health care costs in choosing one candidate over another.

Perhaps even more concerning is the potential for the discovery of a genetic predisposition, like Huntingtons disease. For that individual, somebody who will almost definitely contract the medical condition much later in life, (but not for several decades) the prospect of genetic profiling is downright harrowing. Huntingtons or Parkinsons will present if detected on one genetic profile, but the discovery of its existence may not affect ones health and wellbeing when it is discovered on a healthy individuals profile removed by many decades from actual onset for a given individual. In this case, the intervening event impacting ones health may be completely different, and human resource professionals, hiring managers and employers are ill-equipped to make decisions about the complex science of genomics and therefore use a disclosure as the basis to preclude one from the employment pool. Equally distressing is the idea that health insurance companies would be permitted to use genetic information and big data to inform patterns of underwriting in health insurance.

In the absence of GINA, genetic profiling could be used to determine health insurance rates. Currently, nothing precludes insurance companies from using this data in underwriting life, long-term care and disability insurance as policy makers have historically trailed badly behind this emerging technology. We dont redline neighborhoods anymore, why would we permit the formation of virtual genetic ghettos? Using factors like: race, class, gender, socio-economic status to inform patterns of underwriting in insurance products is bad public policy, why would using genetic predispositions in the form of genotyping be any better?

See more here:
Steve May: The future genetic ghetto - VTDigger - vtdigger.org