PUBLIC RELEASE DATE:

8-Jan-2014

Contact: Susan Gilbert gilberts@thehastingscenter.org 845-424-4040 x244 The Hastings Center

(Garrison, NY) The Center for Research on Ethical, Legal, and Social Implications of Psychiatric, Neurologic, and Behavioral Genetics at Columbia University Medical Center unveils its mission today with the launch of its website. Two Hastings Center research scholars are core faculty members of the new center, which was recently awarded a five-year grant from the National Human Genome Research Institute.

As understanding of the genetic contributions to psychiatric, neurologic, and behavioral (PNB) traits and disorders grows rapidly, this knowledge is quickly being translated into clinical practice. But the information presents particular ethical, legal, and social challenges because of what it could reveal about characteristics associated with individual identity and many of our most feared afflictions. Because of the potential for stigma linked to many PNB disorders and traits, this information may negatively affect how people view themselves and how others see them. Examination of the impact of PNB genetic information and consideration of the implications for normative judgments and public policy are therefore critically needed.

"Scientific findings regarding PNB traits must be discussed with special attention to the human and social context because such traits and disordersfrom Alzheimer's, schizophrenia, and depression to empathy, aggression, and intelligencecan touch our sense of who we are as persons," said Erik Parens, PhD, a senior research scholar at The Hastings Center. Parens and Josephine Johnston, LLB, MBHL, a Hastings Center research scholar and director of research, are core faculty members of the new center, based in the Department of Psychiatry. "The new center is uniquely situated to offer such attention."

The center is focusing on three areas: 1) the impact of PNB genetic information in clinical and research contexts on patients, family members, and clinicians, including effects on treatment choices, health and lifestyle decisions, identity, and self-image; 2) the impact of PNB genetic information in nonclinical contexts in which such information may affect perceptions of autonomy and responsibility for behavior, with a special focus on attributions of responsibility in the judicial process and in everyday life; and 3) data to suggest how PNB genetic information should be used in policy judgments related to clinical contexts (e.g., diagnostic and treatment decisions), research contexts (e.g., access to genetic data), and nonclinical contexts (e.g., legal rules and health policy).

Parens and Johnston will lead the new center's investigation into the meaning of PNB genetics information and how it should be used in policies and practices, as well as the translation of the center's work into formats that can inform policies and practices.

"Our center offers the opportunity to advance knowledge of the ethical, legal, and social implications of one of the most rapidly developing areas of genetics. Drawing on our empirical studies and input from key stakeholders, we will develop strategies to guide the use of PNB genetic data in clinical and research settings, as well as in courts, legislatures, and regulatory agencies," said Paul Appelbaum, MD, director of the center and of the Division of Law, Ethics and Psychiatry in the Department of Psychiatry at Columbia University College of Physicians and Surgeons. "By integrating empirical researchers with experts in ethics, economics, law, and public policy, we hope to point the way toward beneficial use of the latest scientific findings in this exciting new area of genetics."

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New project on psychiatric, neurologic, and behavioral genetics

11 hours ago University of Chicago graduate student Xiao Wang and her colleagues based the results of their Nature paper on RNA modification on analysis of HeLa cells, a line of human cells widely used in laboratory research. Credit: Rob Kozloff/University of Chicago

Researchers had known for several decades that a certain chemical modification exists on messenger ribonucleic acid (mRNA), which is essential to the flow of genetic information. But only recently did experiments at the University of Chicago show that one major function of this modification governs the longevity and decay of RNA, a process critical to the development of healthy cells.

The chemical modification on mRNA in question is called N6-methyladenosine (m6A). A recent study by UChicago scientists reveals how the m6A modification on mRNA could affect the half life of mRNA that in turn regulates cellular protein quantities That discovery could provide fundamental insights into healthy functioning and disorders such as obesity, diabetes, and infertility.

The m6A modification "affects a huge number of messenger RNA in human cells, and yet we did not know its exact function," said Chuan He, professor in chemistry at UChicago and a recently selected investigator of the Howard Hughes Medical Institute. He, Xiao Wang and 11 co-authors from UChicago, University of California, San Diego, and Peking University reported their findings on m6A in the Jan. 2 issue of Nature.

RNA in human cells becomes constantly depleted as it produces proteins, an instability that is essential to biology. "Whenever a cells starts to differentiate, transform into a different type of cell, it needs to express a different set of proteins using a different set of messenger RNA," He said. "It can't be the original set."

The disposal of old RNA allows for the addition of new RNA and the production of different proteins. The Nature study documents that this process is regulated by the insertion or removal of a methyl, a chemical group commonly found in organic compounds.

"Biology is about protein expression regulation: which proteins, how many and at what point," He explained. "If you have the right pattern you get healthy cells. If you get the wrong pattern, you get disease."

It is well known that genetic factors can control protein expression, but the methylation and demethylation of RNA can be epigeneticoperating independent of the sequence of deoxyribonucleic acid (DNA). "This is a very important yet under-explored field," said Wang, the study's lead author and a graduate student in chemistry at UChicago. "It's also a field that is expanding very quickly."

Researchers had long known the presence of the m6A methylation on messenger RNA, but why this occurred remained unknown. He and his associates took a major step in 2011 when they discovered the reverse of the methylation process, demethylation. This discovery involved a so-called "eraser protein" that removed the methyl from RNA, a defect of which leads to obesity. "We basically said, 'Look, if you have certain defect of this function, you get obesity, so there's something going on fundamentally interesting. This methylation appears to play important roles in biological regulation."

He and his associates have now shown that the methylation affects the decay of messenger RNA. "People who are interested in messenger RNA decay or all kinds of cytoplasmic RNA biology now have a new pathway to consider," Wang said.

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Discovery spotlights key role of mystery RNA modification in cells

About 8 million to 12 million years ago, the ancestor of great apes, including humans, underwent a dramatic genetic change. Small pieces of DNA replicated and spread across their resident chromosomes like dandelions across a lawn. But as these dandelion seeds dispersed, they carried some grass and daisy seeds additional segments of DNA along for the ride. This unusual pattern, repeated in different parts of the genome, is found only in great apes bonobos, chimpanzees, gorillas and humans.

I think its a missing piece of human evolution, said Evan Eichler, a geneticist at the University of Washington, in Seattle. My feeling is that these duplication blocks have been the substrate for the birth of new genes.

Over the past few years, scientists have begun to uncover the function of a handful of genes that reside in these regions; they seem to play an important role in the brain, linked to the growth of new cells, as well as brain size and development. In September, Eichlers team published a new technique for analyzing how these genes vary from person to person, which could shed more light on their function.

Clare McLean

Evan Eichler, a geneticist at the University of Washington in Seattle, proposes that bursts of genetic change in our great ape ancestors played a major role in ape and human evolution.

Much about the duplication process and its implications remains a mystery. Eichler and others dont know what spurred the initial rounds of duplications or how these regions, dubbed core duplicons, reproduced and moved around the genome.

Despite the duplication-linked genes potential importance in human evolution, most have not been extensively analyzed. The repetitive structure of the duplicated regions makes them particularly difficult to study using standard genetic approaches the most efficient methods for sequencing DNA start by chopping up the genome, reading the sequence of the small chunks and then assembling those sections like one would a puzzle. Trying to assemble repetitive sections is like trying to put together a puzzle made of pieces with almost the same pattern.

Because these regions are so complex, they are often ignored by conventional genome studies, and some regions still havent been fully sequenced, said James Sikela, a geneticist at the University of Colorado School of Medicine in Aurora. So not only are they important, they are unfortunately unexamined.

A Genetic Burst

In 2007, Eichler and his collaborators took on what seemed like a herculean task looking comprehensively at the repetitive stretches of the human genome. Previous studies had characterized individual regions, but Eichlers team employed new computational techniques and comparative genomics comparing DNA sequences from different species to examine the entire genome. Mathematical analysis published in Nature Genetics that year revealed a set of core duplicons stretches of DNA that appear over and over on a specific chromosome.

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A Missing Genetic Link in Human Evolution | Simons Foundation

Following the Supreme Courts rejection of gene patents, the U.S. proposes steep cuts to reimbursements for breast cancer-gene tests.

That natural human genes cannot be patented was one of the biggest biotechnology stories of 2013 and the effects of that Supreme Court decision are already threatening defendant Myriad Genetics.

The Salt Lake City-based molecular diagnostic company lost the ability to patent DNA sequences of genes known as BRCA1 and BRCA2, which are associated with the risk of developing breast and ovarian cancers (see U.S. Supreme Court Says Natural Human Genes May Not Be Patented). Hours after that decision was announced, other molecular-diagnostics companies announced that they would offer similar tests at a lower cost than Myriads test.

And now, the federal governments Centers for Medicare and Medicaid Services, or CMS, is proposing to lower the amount of money it pays for the tests. The new rate is approximately half of what the agency has previously reimbursed, according to GenomeWeb. The announcement was followed by analyst downgrades on Myriad stock.

CMS directly points to the Supreme Court decision in its announcement and notes that labs charge anywhere from $900 to $2,900 for the test. The new proposed reimbursement amount is $1,438. The proposal will likely lead to lower costs for BRCA testing even when private insurance companies are paying for it, as these companies usually base their rates on those of Medicare, according to the Wall Street Journal.

Myriad is likely to be hardest hit by such price drops because 85 percent of the companys revenue comes from BRCA testing, says the WSJ.

Is this a good deal for patients? With cheaper options available, its reasonable to think that more patients will have access to this testing. But as Robert Nussbaum wrote for MIT Technology Review, Myriad still has an unparalleled record of the natural variation in these important genes. Myriads competitors may offer more affordable tests, but they dont have access Myriads private database linking DNA variations to disease outcomes, a wealth of information the company built up over the years it monopolized BRCA testing. Thats why Nussbaum and colleagues are asking doctors to contribute such vital data for a free, public database that would help doctors interpret the potential effects of a patients BRCA sequences on their cancer risks.

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Cheaper Genetic Tests for Breast Cancer Risks in 2014?

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The Rt Hon Kevin Barron, MP. Member of Parliament for Rother Valley. For political and public service. (Rotherham, South Yorkshire)

Professor Adrian Peter Bird, CBE, FRS, FRSE. Buchanan Professor of Genetics, University of Edinburgh. For services to Science. (Edinburgh)

Professor Richard William Blundell, CBE, FBA. Professor of Economics, UCL and director, ESRC Centre for the Micro-Economic Analysis of Public Policy IFS. For services to Economics and Social Science. (London)

Ian Michael Cheshire. Chief executive, Kingfisher plc. For services to Business, Sustainability and the Environment. (London)

Michael Victor Codron, CBE. For services to the Theatre. (London)

Paul Collier, CBE. For services to promoting research and policy change in Africa. (Oxford, Oxfordshire)

David Nigel Dalton. Chief executive, Salford Royal NHS Foundation Trust. For services to Healthcare. (Willaston, Cheshire)

Roger Michael De Haan, CBE, DL. Philanthropist. For services to Education and to charity in Kent and Overseas. (Ashford, Kent)

Michael Roger Gifford. Formerly Lord Mayor of London. For services to International Business, Culture and the City of London. (London)

Antony Mark David Gormley, OBE. Sculptor. For services to the Arts. (London)

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New Year Honours 2014: list in full

PUBLIC RELEASE DATE:

25-Dec-2013

Contact: Emily Ng eng3@nshs.edu 516-562-2670 North Shore-Long Island Jewish (LIJ) Health System

MANHASSET, NY An international group of investigators has discovered new genes, pathways and cell types that are involved in inherited susceptibility to rheumatoid arthritis (RA). The findings are published online in Nature.

Scientists performed a genome-wide association study (GWAS) meta-analysis in more than 100,000 people of European and Asian descent. They discovered 42 new sites of genetic variation involved in risk for RA. The analysis provides specific locations of genes, DNA sequences or positions on chromosomes for these genetic differences, bringing the catalog of confirmed risk variants for RA to over 100 genetic loci. These findings lead to a better understanding of how new treatments could be developed.

"This study is the culmination of over a decade of work by an extraordinary group of collaborative scientists from around the world," said Peter K. Gregersen, a collaborator on the study, and head of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute for Medical Research. "It provides us with a definitive list of the major common genetic variation involved in this disease, and points the way forward to develop new diagnostic and therapeutic approaches to this illness."

The lead investigator of the study, Robert Plenge, MD, PhD, director of Genetics and Genomics, Division of Rheumatology, Immunology and Allergy at Brigham and Women's Hospital added, "Our study provides a compelling link between human genetics in RA and approved therapies to treat RA. This leads to an intriguing question: can our new genetic discoveries lead to new therapies to treat or cure RA? Further, can a similar approach be used to develop therapies for other complex diseases such as lupus, diabetes and Alzheimer's disease?"

Rheumatoid arthritis is a long-term inflammatory disorder that may affect many tissues and organs, but principally attacks flexible joints. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated. The disease often leads to the destruction of cartilage and fusion of the joints. Rheumatoid arthritis can also produce inflammation in areas of the body including the lungs, membrane around the heart, and white of the eye.

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Feinstein Institute researchers are conducting studies on rheumatoid arthritis, both on genetics as well as to identify targets for the development of new therapies. To learn more, visit http://www.FeinsteinInstitute.org.

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Researchers complete a milestone in defining the genetic basis of rheumatoid arthritis

Human genetic variation is the genetic differences both within and among populations. There may be multiple variants of any given gene in the human population (genes), leading to polymorphism. Many genes are not polymorphic, meaning that only a single allele is present in the population: the gene is then said to be fixed.[1] On average, biochemically all humans are 99.9% similar to any other humans.[2]

No two humans are genetically identical. Even monozygotic twins, who develop from one zygote, have infrequent genetic differences due to mutations occurring during development and gene copy number variation.[3] Differences between individuals, even closely related individuals, are the key to techniques such as genetic fingerprinting. Alleles occur at different frequencies in different human populations, with populations that are more geographically and ancestrally remote tending to differ more.

Causes of differences between individuals include the exchange of genes during meiosis and various mutational events. There are at least two reasons why genetic variation exists between populations. Natural selection may confer an adaptive advantage to individuals in a specific environment if an allele provides a competitive advantage. Alleles under selection are likely to occur only in those geographic regions where they confer an advantage. The second main cause of genetic variation is due to the high degree of neutrality of most mutations. Most mutations do not appear to have any selective effect one way or the other on the organism. The main cause is genetic drift, this is the effect of random changes in the gene pool. In humans, founder effect and past small population size (increasing the likelihood of genetic drift) may have had an important influence in neutral differences between populations. The theory that humans recently migrated out of Africa supports this.

The study of human genetic variation has both evolutionary significance and medical applications. It can help scientists understand ancient human population migrations as well as how different human groups are biologically related to one another. For medicine, study of human genetic variation may be important because some disease-causing alleles occur more often in people from specific geographic regions. New findings show that each human has on average 60 new mutations compared to their parents.[4][5] Apart from mutations, many genes that may have aided humans in ancient times plague humans today. For example, it is suspected that genes that allow humans to more efficiently process food are those that make people susceptible to obesity and diabetes today.[6]

Genetic variation among humans occurs on many scales, from gross alterations in the human karyotype to single nucleotide changes.[7]

Nucleotide diversity is the average proportion of nucleotides that differ between two individuals. The human nucleotide diversity is estimated to be 0.1%[8] to 0.4% of base pairs.[9] A difference of 1 in 1,000 amounts to approximately 3 million nucleotide differences, because the human genome has about 3 billion nucleotides.

A single nucleotide polymorphism (SNP) is difference in a single nucleotide between members of one species that occurs in at least 1% of the population. It is estimated that there are 10 to 30 million SNPs in humans.

SNPs are the most common type of sequence variation, estimated to comprise 90% of all sequence variations.[10] Other sequence variations are single base exchanges, deletions and insertions.[10] SNPs occur on average about every 100 to 300 bases [10] and so are the major source of heterogeneity.

A functional, or non-synonymous, SNP is one that affects some factor such as gene splicing or messenger RNA, and so causes a phenotypic difference between members of the species. About 3% to 5% of human SNPs are functional (see International HapMap Project). Neutral, or synonymous SNPs are still useful as genetic markers in genome-wide association studies, because of their sheer number and the stable inheritance over generations.[10]

A coding SNP is one that occurs inside a gene. There are 105 Human Reference SNPs that result in premature stop codons in 103 genes. This corresponds to 0.5% of coding SNPs. They occur due to segmental duplication in the genome. These SNPs result in loss of protein, yet all these SNP alleles are common and are not purified in negative selection.[11]

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Human genetic variation - Wikipedia, the free encyclopedia

GAINESVILLE, Fla., Dec. 23 (UPI) -- Human-induced climate change may pose a bigger threat than first believed to plants and global agriculture, a University of Florida scientist says.

Evolutionary genetics Professor Pam Soltis, co-author of a study published in the journal Nature, said most flowering plants, trees and agricultural crops may not have the evolutionary traits needed to rapidly respond to human-induced climate change.

Many of these plants needed millions of years to evolve mechanisms to cope with freezing temperatures as they radiated into nearly every climate during pre-historic times, she said, and likely acquired many of these adaptive traits prior to their movement into colder regions.

"Only some plants were able to make the adjustments to survive in cold climates," Soltis said in a university release Friday. "In fact, some had traits used for other purposes that they co-opted for cold tolerance. The results have implications for plant response to climate change -- some plant lineages, including many crops, will not have the underlying genetic attributes that will allow for rapid responses to climate change."

Because evolutionary strategies to resist cold would have taken millions of years, researchers said, it could mean many plants will have trouble with accelerating human-caused climate change.

"Some of these changes were probably not as simple as we once thought," Soltis said. "Adjusting to big shifts in their environments is probably not easy for plants to do.

"With climate change that is human-induced, all habitats will be affected over a short period of time, and plants and other organisms will have to adapt quickly if they are to survive," she said.

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Newswise BIRMINGHAM, Ala. Changes to a gene called LZTR1 predispose people to develop a rare disorder where multiple tumors called schwannomas form near nerve pathways, according to a study published today in the journal Nature Genetics and led by researchers from the University of Alabama at Birmingham.

The formation of multiple schwannomas is one sign that a person has the genetic disorder called schwannomatosis, which is one of the three major forms of neurofibromatosis, besides neurofibromatosis types 1 and 2. The condition is so named because the tumors originate in Schwann cells that form in sheaths that insulate nerves to cause severe, chronic pain in many patients.

To date, physicians cannot give most patients a confirmed diagnosis for schwannomatosis, even if they show symptoms, because changes in genes linked to the condition by past studies explain only about 50 percent of familial and less than 10 percent of sporadic cases.

Work in 2007 determined that inheritable mutations in SMARCB1 predisposed to schwannomatosis. In addition, the schwannomas showed a loss of the long arm of chromosome 22, and different mutations in the neurofibromatosis type 2 (NF2) gene were found in each tumor studied.

Despite these many known details, much of the risk for schwannomatosis remained unexplained going into the current study. Several research groups had proposed that other schwannomatosis-predisposing genes existed, but no one had found any. Specializing in genetic studies for all forms of the neurofibromatoses, the UAB Medical Genomics Laboratory chose to focus its research on a subset of schwannomatosis samples that did not harbor SMARCB1 mutations, which framed their experiments such that the role of LZTR1 was revealed.

We have been working urgently to identify the genetic mechanisms behind these diseases because doing so is central to efforts to understand schwannoma tumor development as well as to identify new drug treatments, said Ludwine Messiaen, Ph.D., director of the Medical Genomics Laboratory, professor in the Division of Clinical Genetics in the Department of Genetics within the UAB School of Medicine and corresponding study author. This is pertinent as only some of the schwannomas can be surgically removed without neurological consequences, and there is no widely accepted approach for treating the severe, chronic pain in these patients.

The study, conceived and coordinated by Arkadiusz Piotrowski of the University of Gdansk in Poland and Messiaen, resulted in the identification of LZTR1 on chromosome 22q as a novel tumor-suppressor gene predisposing to multiple schwannomas in patients without a mutation in SMARCB1. The results were seen in patients whose schwannomas also showed a loss of the long arm of chromosome 22 and a different somatic NF2 mutation in each tumor. The team found that in all 25 schwannomas studied from 16 unrelated schwannomatosis patients, all tumors showing a loss of the long arm of chromosome 22 and a different somatic NF2 mutation in each tumor also had LZTR1 mutations present, strongly supporting the contribution to the disease by the combination of these factors.

The LZTR1 mutations were found using massive parallel sequencing (e.g. next-generation sequencing) of highly evolutionary conserved sequences specifically on chromosome 22. LZTR1 mutations likely will be found in a high fraction of familial as well as sporadic schwannomatosis patients, whose predisposition is not caused by SMARCB1, says Messiaen. Indeed, LZTR1 mutations were found in 6/6 familial and 8/11 sporadic such patients. Both causal genes, LZTR1 and SMARCB1, show a potential functional link to chromatin remodeling mechanisms, which play a crucial role in cell differentiation and adaptation to environmental stimuli. Further, LZTR1 and SMARCB1 are known to interact with histone deacetylase 4 or HDAC4, which is a target for histone deacetylase inhibitors, a new class of anti-tumor drugs. The present findings will encourage further studies aiming at potential treatment for schwannomatosis.

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Changes in Gene Explain More of Inherited Risk for Rare Disease

Whole Genome CN in Stratification and Diagnosis of Brain Tumor Patients
Dr. Pietsch shares his experiences in more than 600 FFPE brain tumor biopsies from the Institute of Neuropathology, University of Bonn Medical Center. This p...

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Volume93,Issue 6:December5,2013

On the cover: John Borden Graham, M.D., President, American Society of Human Genetics, 1972. John Graham is remembered as a pioneer in the genetics of blood coagulation and genetics education. He was born in 1918 in Goldsboro and earned a bachelors degree from Davidson College in 1938. He began his medical training by studying the basic sciences at University of North Carolina at Chapel Hill (UNC-CH) and completed his M.D. at Cornell University in 1942. After a short pathology residency, he entered the US Army, where he served as a surgeon in the Pacific Theater. He returned to Chapel Hill in 1946 to join the Department of Pathology as an instructor. He remained at UNC-CH until his formal retirement in 1985. Graham continued to participate in departmental activities and attended departmental grand rounds until the day before his death in 2004. In 1954, Graham established the first formal course in medical genetics at UNC-CH. Grahams research focused on hematology and blood clotting initially through collaboration with Kenneth Brinkhous, who was characterizing canine hemophilia. Together, they demonstrated X-linkage and viability of homozygous females (Brinkhous and Graham [1950]. Science 111, 723724). He is credited with the characterization of clotting factor X and X-linked vitamin-D-resistant rickets. He remembered when the Society numbered 200 members in 1954 and that meetings were held during summer vacations on university campuses with families in tow. He contrasted those days with the very large Society meetings held at posh urban hotels in the mid-1980s (Graham [1985], Norma Berryhill Distinguished Lecture, https://secure.dev.unc.edu/MedFound/graham13-27.pdf). Although no recording of his presidential address from the 1972 annual meeting held in Philadelphia can be found, some of Grahams articles represent recorded presentations. Examples include his 1956 review of hemophilia drawn from a session at the 1955 ASHG annual meeting (Am. J. Hum. Genet. 8, 6379) and a 1959 discussion on vascular hemophilia, which includes references to Homers Odyssey (J. Med. Educ. 34, 385396). These allow the reader to enjoy Grahams garrulous and erudite style. This image of Graham was drawn by Peter James Field from a photograph provided by the University of North Carolina Department of Pathology and is used with permission.

Click here for a high-resolution version of the cover.

Each week, The American Journal of Human Genetics publishes papers online ahead of the print issue. Here are the latest:

All in the Family In the age of next-generation sequencing, linkage analysis might seem old fashioned, and perhaps even ill suited for the pursuit of variants that contribute to complex phenotypes. Indeed, many have turned to genome-wide association studies and exome-wide sequencing studies for such investigations. In this issue, Rosenthal et al. show that family studies can be adapted, and indeed strengthened, by the integration with 21st century technology and resources. Through a combination of linkage analysis and exome sequencing, the authors identified a SLC25A40 missense change that might contribute to high triglyceride levels. They then harnessed the power of the NHLBI Exome Sequencing Project to identify an association between SLC25A40 variants and high triglyceride levels.

Regulating lincRNA Expression Unlike that of protein-coding genes, the function of the majority of large intergenic noncoding RNAs (lincRNAs) remains unknown. To gain further insight into the potential roles of lincRNAs, Popadin et al. used a genome-wide approach to characterize the cis expression quantitative trait loci (cis-eQTLs) and DNA-methylation patterns that contribute to lincRNA expression variability across fibroblasts, lymphoblastoid cell lines, and T cells derived from 195 European individuals. In general, lincRNA cis-eQTLs affected neighboring downstream protein-coding genes, suggesting that lincRNAs might also act as enhancers. Because lincRNAs are relatively young, it remains to be seen whether the variants that contribute to variable expression are under selection.

Functional Characterization of Breast-Cancer-Associated SNPs Variants near FGFR2 have been implicated in estrogen receptor (ER)-positive breast cancer, but it remains unclear how this locus contributes to disease progression. In this study, Meyer et al. used the iCOGS chip to fine map this region. They identified three independent risk signals and further prioritized the variants by using a variety of assays. ChIP assays demonstrated allele-specific binding of FOXA1 and E2F1. Because FOXA1 and ER are involved in conferring estrogen responsiveness, these results support the involvement of this locus in ER-positive breast cancer.

Ciliary Involvement in Morbid Obesity Substantial effort has been spent on identifying genes that are associated with obesity and metabolic dysfunction. In this issue, Shalata and colleagues identified a homozygous nonsense mutation in CEP19 in a large, consanguineous family where affected individuals are morbidly obese and have an average body mass index of 48.7. Moreover, Cep19-knockout mice were nearly twice as heavy as their wild-type littermates, as well as hyperphagic, glucose intolerant, and insulin resistant in comparison to the wild-type mice. CEP19 localized to the centriole and basal body of primary cilia, suggesting the need for further explorations into the role of cilia in regulating metabolism.

Exploring T2D Exomes In recent years, the hunt for variants associated with common diseases has focused on uncovering common variants. More recently, however, spurred by the decreased cost of sequencing, investigators have begun to search for rare variants of large effect. In this issue, Lohmueller et al. explore the possibility that the underlying genetic architecture of type 2 diabetes (T2D) is driven by rare variants clustered in a small number of genes. Single-marker and gene-based association tests failed to reveal significant associations, suggesting that if rare variants do contribute to T2D risk, they will not be limited to a small number of genes.

A Polymorphism in IRF4 Affects Human Pigmentation through a Tyrosinase-Dependent MITF/TFAP2A Pathway In this study, Praetorius et al. demonstrate that a SNP associated with sun-exposure sensitivity lies within a melanocyte-specific enhancer of IRF4 transcription, thus identifying a noncoding polymorphism that affects a phenotype through modulation of a developmental gene regulatory network.

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Human genetics is the study of inheritance as it occurs in human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, population genetics, developmental genetics, clinical genetics, and genetic counseling.

Genes can be the common factor of the qualities of most human-inherited traits. Study of human genetics can be useful as it can answer questions about human nature, understand the diseases and development of effective disease treatment, and understand genetics of human life. This article describes only basic features of human genetics; for the genetics of disorders please see: Medical genetics.

Inheritance of traits for humans are based upon Gregor Mendel's model of inheritance. Mendel deduced that inheritance depends upon discrete units of inheritance, called factors or genes.[1]

Autosomal traits are associated with a single gene on an autosome (non-sex chromosome)they are called "dominant" because a single copyinherited from either parentis enough to cause this trait to appear. This often means that one of the parents must also have the same trait, unless it has arisen due to a new mutation. Examples of autosomal dominant traits and disorders are Huntington's disease, and achondroplasia.

Autosomal recessive traits is one pattern of inheritance for a trait, disease, or disorder to be passed on through families. For a recessive trait or disease to be displayed two copies of the trait or disorder needs to be presented. The trait or gene will be located on a non-sex chromosome. Because it takes two copies of a trait to display a trait, many people can unknowingly be carriers of a disease. From an evolutionary perspective, a recessive disease or trait can remain hidden for several generations before displaying the phenotype. Examples of autosomal recessive disorders are albinism, cystic fibrosis, Tay-Sachs disease.

X-linked genes are found on the sex X chromosome. X-linked genes just like autosomal genes have both dominant and recessive types. Recessive X-linked disorders are rarely seen in females and usually only affect males. This is because males inherit their X chromosome and all X-linked genes will be inherited from the maternal side. Fathers only pass on their Y chromosome to their sons, so no X-linked traits will be inherited from father to son. Men cannot be carriers for recessive X linked traits, as they only have one X chromosome, so any X linked trait inherited from the mother will show up.

Females express X-linked disorders when they are homozygous for the disorder and become carriers when they are heterozygous. X-linked dominant inheritance will show the same phenotype as a heterozygote and homozygote. Just like X-linked inheritance, there will be a lack of male-to-male inheritance, which makes it distinguishable from autosomal traits. One example of a X-linked trait is Coffin-Lowry syndrome, which is caused by a mutation in ribosomal protein gene. This mutation results in skeletal, craniofacial abnormalities, mental retardation, and short stature.

X chromosomes in females undergo a process known as X inactivation. X inactivation is when one of the two X chromosomes in females is almost completely inactivated. It is important that this process occurs otherwise a woman would produce twice the amount of normal X chromosome proteins. The mechanism for X inactivation will occur during the embryonic stage. For people with disorders like trisomy X, where the genotype has three X chromosomes, X-inactivation will inactivate all X chromosomes until there is only one X chromosome active. Males with Klinefelter syndrome, who have an extra X chromosome, will also undergo X inactivation to have only one completely active X chromosome.

Y-linked inheritance occurs when a gene, trait, or disorder is transferred through the Y chromosome. Since Y chromosomes can only be found in males, Y linked traits are only passed on from father to son. The testis determining factor, which is located on the Y chromosome, determines the maleness of individuals. Besides the maleness inherited in the Y-chromosome there are no other found Y-linked characteristics.

A pedigree is a diagram showing the ancestral relationships and transmission of genetic traits over several generations in a family. Square symbols are almost always used to represent males, whilst circles are used for females. Pedigrees are used to help detect many different genetic diseases. A pedigree can also be used to help determine the chances for a parent to produce an offspring with a specific trait.

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Human genetics - Wikipedia, the free encyclopedia

Dr. Karin Blakemore
Dr. Blakemore is the Director of Maternal Fetal Medicine and Prenatal Genetics whose clinical practice focuses on caring for expectant mothers and their deve...

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Video Now Available Genetics and Genomics of Thyroid Neoplasms On Dec. 6th, Electron Kebebew, M.D., chief of the Endocrine Oncology Branch, National Cancer Institute, NIH, presented Genetics and Genomics of Thyroid Neoplasms: Moving Closer Towards Personalized Patient Care, as part of the 2013-2014 Genomics in Medicine Lecture Series, sponsored by NHGRI in collaboration with Suburban Hospital and Johns Hopkins. Video of his talk is now available. See the video Presidential Bioethics Report on Incidental Findings The Presidential Commission for the Study of Bioethical Issues released a report on Dec. 12, 2013, entitled Anticipate and Communicate: Ethical Management of Incidental and Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts. Although not specifically focused on genomics, the report and its guidelines have implications for genomics research and medicine. Read the report Read the press release The Genomics Landscape Jumping into the deep end of genomic medicine When NHGRI published its new strategic vision for genomics in 2011, we recognized that we had a lot to learn about the research needed to apply genomics to clinical care. At the same time, it seemed critical that we begin to establish a foundation of research programs that would facilitate the implementation of genomic medicine, so we decided to jump in and start swimming! Read more Video Now Available The African Diaspora: Integrating Culture, Genomics and History Videos of the symposium "The African Diaspora: Integrating Culture, Genomics and History" are now available. The event included talks on using genomics in ancestral research and differences in health. NHGRI organized the symposium with the Smithsonian National Museum of Natural History and the National Museum of African American History and Culture. Watch the videos

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CHICAGO (AP) Dr. Janet Rowley, a pioneer in cancer genetics research, has died at age 88.

Rowley spent most of her career at the University of Chicago, where she also obtained her medical degree. She died Tuesday of ovarian cancer complications at her home nearby, the university said in a statement.

Rowley conducted landmark research with leukemia in the 1970s, linking cancer with genetic abnormalities work that led to targeted drug treatment for leukemia. She identified a genetic process called translocation, now widely accepted. By 1990, more than 70 translocations had been identified in various cancers, according to her biography on the National Library of Medicine's website.

She is a recipient of the National Medal of Science, the nation's highest scientific honor and the Presidential Medal of Freedom, the nation's highest civilian honor.

"Janet Rowley's work established that cancer is a genetic disease," Mary-Claire King, president of the American Society of Human Genetics, said recently. "We are still working from her paradigm."

Rowley, known among colleagues for her intelligence and humility, called receiving the presidential award, in 2009, "quite remarkable."

"I've never regretted being in science and being in research," Rowley said at the time. "The exhilaration that one gets in making new discoveries is beyond description."

With her silvery hair and twinkling eyes, Rowley was a recognizable figure at the University of Chicago, often seen riding her bike around the South Side campus, even up until a few months ago despite her disease. She remained active in research until close to her death and hoped that her own cancer could contribute to understanding of the disease.

Just last month, she was well enough to attend a celebration of the 50th anniversary of the presidential medal in Washington alongside other previous recipients and this year's winners, who include several scientists, former President Bill Clinton, Oprah Winfrey, baseball's Ernie Banks and Loretta Lynn.

Rowley was born in New York City in 1925 and at age 15 won a scholarship to an advanced academic program at the University of Chicago. She went to medical school there when the quota was just three women in a class of 65, the university said.

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Janet Rowley, cancer genetics pioneer, dies at 88

Human evolutionary genetics studies how one human genome differs from the other, the evolutionary past that gave rise to it, and its current effects. Differences between genomes have anthropological, medical and forensic implications and applications. Genetic data can provide important insight into human evolution.

Biologists classify humans, along with only a few other species, as great apes (species in the family Hominidae). The Hominidae include two distinct species of chimpanzee (the bonobo, Pan paniscus, and the common chimpanzee, Pan troglodytes), two species of gorilla (the western gorilla, Gorilla gorilla, and the eastern gorilla, Gorilla graueri), and two species of orangutan (the Bornean orangutan, Pongo pygmaeus, and the Sumatran orangutan, Pongo abelii).

Apes, in turn, belong to the primates order (>400 species). Data from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) indicate that primates belong to the group of Euarchontoglires, together with Rodentia, Lagomorpha, Dermoptera, and Scandentia.[1] This is further supported by Alu-like short interspersed nuclear elements (SINEs) which have been found only in members of the Euarchontoglires.[2]

A phylogenetic tree like the one shown above is usually derived from DNA or protein sequences from populations. Often mitochondrial DNA or Y chromosome sequences are used to study ancient human demographics. These single-locus sources of DNA do not recombine and are almost always inherited from a single parent, with only one known exception in mtDNA.[3] Individuals from the various continental groups tend to be more similar to one another than to people from other continents. The tree is rooted in the common ancestor of chimpanzees and humans, which is believed to have originated in Africa. Horizontal distance in the diagram corresponds to two things:

Chimpanzees and humans belong to different genera, indicated in red. Formation of species and subspecies is also indicated, and the formation of races is indicated in the green rectangle to the right (note that only a very rough representation of human phylogeny is given). Note that vertical distances are not meaningful in this representation.

The separation of humans from their closest relatives, the African apes (chimpanzees and gorillas), has been studied extensively for more than a century. Five major questions have been addressed:

As discussed before, different parts of the genome show different sequence divergence between different hominoids. It has also been shown that the sequence divergence between DNA from humans and chimpanzees varies greatly. For example the sequence divergence varies between 0% to 2.66% between non-coding, non-repetitive genomic regions of humans and chimpanzees.[5] Additionally gene trees, generated by comparative analysis of DNA segments, do not always fit the species tree. Summing up:

The divergence time of humans from other apes is of great interest. One of the first molecular studies, published in 1967 measured immunological distances (IDs) between different primates.[7] Basically the study measured the strength of immunological response that an antigen from one species (human albumin) induces in the immune system of another species (human, chimpanzee, gorilla and Old World monkeys). Closely related species should have similar antigens and therefore weaker immunological response to each other's antigens. The immunological response of a species to its own antigens (e.g. human to human) was set to be 1.

The ID between humans and gorillas was determined to be 1.09, that between humans and chimpanzees was determined as 1.14. However the distance to six different Old World monkeys was on average 2.46, indicating that the African apes are more closely related to humans than to monkeys. The authors consider the divergence time between Old World monkeys and hominoids to be 30 million years ago (MYA), based on fossil data, and the immunological distance was considered to grow at a constant rate. They concluded that divergence time of humans and the African apes to be roughly ~5 MYA. That was a surprising result. Most scientists at that time thought that humans and great apes diverged much earlier (>15 MYA).

The gorilla was, in ID terms, closer to human than to chimpanzees; however, the difference was so slight that the trichotomy could not be resolved with certainty. Later studies based on molecular genetics were able to resolve the trichotomy: chimpanzees are phylogenetically closer to humans than to gorillas. However, the divergence times estimated later (using much more sophisticated methods in molecular genetics) do not substantially differ from the very first estimate in 1967.

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Human evolutionary genetics - Wikipedia, the free encyclopedia

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Newswise Singapore, 18 December 2013 A recent study led by scientists from the National University of Singapore (NUS) opens a possible new route for treatment of Spinal Muscular Atrophy (SMA), a devastating disease that is the most common genetic cause of infant death and also affects young adults. As there is currently no known cure for SMA, the new discovery gives a strong boost to the fight against SMA.

SMA is caused by deficiencies in the Survival Motor Neuron (SMN) gene. This gene controls the activity of various target genes. It has long been speculated that deregulation of some of these targets contributes to SMA, yet their identity remained unknown.

Using global genome analysis, the research team, led by Associate Professor Christoph Winkler of the Department of Biological Sciences at the NUS Faculty of Science and Dr Kelvin See, a former A*STAR graduate scholar in NUS who is currently a Research Fellow at the Genome Institute of Singapore (GIS), found that deficiency in the SMN gene impairs the function of the Neurexin2 gene. This in turn limits the neurotransmitter release required for the normal function of nerve cells. The degeneration of motor neurons in the spinal cord causes SMA. This is the first time that scientists establish an association between Neurexin2 and SMA.

Preliminary experimental data also showed that a restoration of Neurexin2 activity can partially recover neuron function in SMN deficient zebrafish. This indicates a possible new direction for therapy of neurodegeneration.

Collaborating with Assoc Prof Winkler and the NUS researchers are Dr S. Mathavan and his team at GIS, as well as researchers from the University of Wuerzburg in Germany. The breakthrough discovery was first published in scientific journal Human Molecular Genetics last month.

Small zebrafish provides insights into human neurodegenerative disease

SMA is a genetic disease that attacks a distinct type of nerve cells called motor neurons in the spinal cord. The disease has been found to be caused by a defect in the SMN gene, a widely used gene that is responsible for normal motor functions in the body.

To study how defects in SMN cause neuron degeneration, the scientists utilised a zebrafish model, as the small fish has a relatively simple nervous system that allows detailed imaging of neuron behaviour.

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Study Provides New Insights Into Cause of Human Neurodegenerative Disease