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Archive - 2013

October 24th

BROCA Panel Provides Comprehensive Testing of All Known Breast Cancer Genes

Since 1994, many thousands of women with breast cancer from families severely affected with the disease have been tested for inherited mutations in BRCA1 and BRCA2 by the Myriad Genetics test. The vast majority of those patients were told that their gene sequences were normal. With the development of modern genomics sequencing tools, the discovery of additional genes implicated in breast cancer, and the change in the legal status of genetic testing for BRCA1 and BRCA2 due to the June 13, 2013 U.S. Supreme Court decision to bar the patenting of naturally occurring genes that ended Myriad’s monopoly on the testing for BRCA1 and BRCA2 mutations, it is now possible to determine how often families in these circumstances actually do carry cancer-predisposing mutations in BRCA1, BRCA2, or any of a number of breast cancer-associated genes, despite the results of their previous genetic tests. This was the challenge addressed by Mary-Claire King (photo), Ph.D., American Cancer Society Professor of Medicine and Genome Sciences at the University of Washington, Seattle, past President of the ASHG, and renowned breast cancer genetic researcher; and Tomas Walsh, Ph.D., Associate Research Professor of Medical Genetics, also at the University of Washington, Seattle. The researchers conducted complete genomic sequencing of all genes known to be implicated in breast cancer on DNA samples from breast cancer patients who had normal BRCA1 and BRCA2 commercial test results (Myriad testing). The commercial testing occurred because the patients had a severe family history of breast cancer, defined as a family with three or more relatives affected by breast or ovarian cancer. The results were presented today by Dr. Walsh at the American Society of Human Genetics 2013 annual meeting in Boston.

Rare Mutations in RINT1 Tumor Suppressor Gene Associated with Early-Onset Breast Cancer and Possibly Other Cancers

An international team of scientists has identified an association between heritable, rare mutations in the RINT1 gene and increased risk of early-onset breast cancer, according to research reported today (October 24) at the American Society of Human Genetics (ASHG) 2013 Annual Meeting in Boston. The rare mutations in RINT1, a tumor suppressor gene, were detected in 3 of 49 families participating in a study that sequenced the whole exome, the protein-coding DNA, of families with multiple individuals affected by breast cancer. “Although mutations in RINT1 are rare, it is most likely that the remaining unknown breast cancer susceptibility genes will account for similar small proportions of the disease,” said Daniel J. Park, Ph.D., who presented the study at ASHG 2013 and is Senior Research Fellow in genetic epidemiology at the University of Melbourne, Australia. Only approximately 35 percent of the familial risk for breast cancer has been explained so far, according to Dr. Park and his collaborators, who added that the discovery of the RINT1 variants’ association with the disease could help members of families with multiple cases of breast cancer to identify their individual risk for developing the cancer. Dr. Park’s collaborators in the search for unidentified breast cancer susceptibility genes are scientists at the Institute Curie in Paris, the International Agency for Research on Cancer in Lyon, France, the Huntsman Cancer Institute in Salt Lake City, Utah, as well as the University of Melbourne.

October 23rd

“The Play’s the Thing” at American Society of Human Genetics Annual Meeting in Boston

A provocative new interactive play, “The Drama of DNA: Anticipating the Future with WGS,” was performed by a cast of distinguished genomics professionals on the first evening, Tuesday, October 22, of the 2013 American Society of Human Genetics (ASHG) annual meeting in Boston. The play was hugely popular. It was sold out two weeks after the availability of tickets was announced and at the end of the play many in the audience were asking how they could implement such an innovative approach at their own institution or organization. In the play, fictionalized characters explored a hypothetical research protocol in which the entire DNA codes of children diagnosed with autism spectrum disorder (ASD), their “unaffected” siblings and parents, including their pregnant mothers, would be deciphered. The play brought to life the challenges and potential implications of using whole genome sequencing (WGS) in research and medicine, said the co- authors, Lynn W. Bush, Ph.D., M.S., M.A., and Karen Rothenberg, J.D., M.P.A. Dr. Bush, a psychologist and bioethicist, is on the faculty of pediatric clinical genetics at Columbia University. Rothenberg, the founding director of the Law and Health Care program and Professor at the University of Maryland School of Law, is Senior Advisor on Genomics and Society to the National Human Genome Research Institute (NHGRI) Director Eric D. Green, M.D., Ph.D., one of the play’s 13 “actors” who performed in the play. Among the other genomics professionals who participated in the play were: Carlos Bustamante, Ph.D., Professor of Genetics, Stanford School of Medicine; Vence Bonham, J.D., Chief of the Education and Involvement Branch of the NHGRI; Jeff Botkin, M.D., M.P.H.., Chief of Medical Ethics, University of Utah Health Care; Malia Fullerton, D.

Gone Today, Hair Tomorrow

Researchers at Columbia University Medical Center (CUMC) and collaborators at Durham University in the UK have devised a hair restoration method that can generate new human hair growth, rather than simply redistribute hair from one part of the scalp to another. The approach could significantly expand the use of hair transplantation to women with hair loss, who tend to have insufficient donor hair, as well as to men in the early stages of baldness. The study was published on October 21, 2013 in the online edition of PNAS. “About 90 percent of women with hair loss are not strong candidates for hair transplantation surgery because of insufficient donor hair,” said co-study leader Angela M. Christiano, Ph.D., the Richard and Mildred Rhodebeck Professor of Dermatology and professor of genetics & development at CUMC. “This method offers the possibility of inducing large numbers of hair follicles or rejuvenating existing hair follicles, starting with cells grown from just a few hundred donor hairs. It could make hair transplantation available to individuals with a limited number of follicles, including those with female-pattern hair loss, scarring alopecia, and hair loss due to burns.” According to Dr. Christiano, such patients gain little benefit from existing hair-loss medications, which tend to slow the rate of hair loss but usually do not stimulate robust new hair growth. “Dermal papilla cells give rise to hair follicles, and the notion of cloning hair follicles using inductive dermal papilla cells has been around for 40 years or so,” said co-study leader Colin Jahoda, Ph.D., professor of stem cell sciences at Durham University, England, and co-director of North East England Stem Cell Institute, who is one of the early founders of the field.

October 22nd

Gene-Silencing Strategy Opens New Path to Understanding Down Syndrome

The first evidence that the underlying genetic defect responsible for trisomy 21, also known as Down syndrome, can be suppressed in laboratory cultures of patient-derived stem cells was presented today (October 22) at the opening of the American Society of Human Genetics (ASHG) 2013 annual meeting in Boston, running through October. The ASHG annual meeting is the world's largest gathering of human genetics professionals and a forum for renowned experts in the field.People with Down syndrome are born with an extra chromosome 21, which results in a variety of physical and cognitive ill effects. In laboratory cultures of cells from patients with Down syndrome, an advanced genome editing tool was successfully used to silence the genes on the extra chromosome, thereby neutralizing it, said Jeanne Lawrence, Ph.D., Professor of Cell & Developmental Biology at the University Massachusetts Medical School, Worcester, Massachusetts. Dr. Lawrence and her team compared trisomic stem cells derived from patients with Down syndrome, in which the extra chromosome 21 was silenced, to identical cells from patients that were untreated. The researchers identified defects in the proliferation, or rapid growth, of the untreated cells and the differentiation, or specialization, of untreated nervous system cells. These defects were reversed in trisomic stem cells in which the extra chromosome 21 was muted. “Silencing of trisomy 21 by manipulation of a single gene in living cells in laboratory cells surmounts the first major obstacle to development of potential ‘chromosome therapy,’” said Dr. Lawrence, whose presentation today provided an update to the results that she and her colleagues reported earlier this year in the journal Nature (Jiang et al. 2013). In her ASHG presentation, Dr.

Opportunities and Risks of Personal Genomics Are Key Topics of Sunday’s Session of the World Congress of Psychiatric Genetics in Boston

Sunday’s (October 20) portion of the five-day 2013 XXIst World Congress of Psychiatric Genetics opened with a plenary session on the “Opportunities and Risks Associated with Personal & Clinical Genomics.” The format was a panel presentation chaired by Robert C. Green, M.D., M.P.H., Associate Professor of Medicine in the Division of Genetics at Brigham and Women’s Hospital and Harvard Medical School, Associate Director for Research at Partners Health Care for Personalized Genetic Medicine, and Director of Genes2People (GTP). The four distinguished panelists were Paul Appelbaum, M.D., Professor of Psychiatry, Medicine, & Law and Director of the Division of Law, Ethics, and Psychiatry in the Department of Psychiatry at Columbia University; Atul Butte, M.D., Ph.D., Chief of the Division of Systems Medicine and Associate Professor of Pediatrics, Medicine, and Computer Science at Stanford University and Lucile Packard Children's Hospital, and a co-founder of Personalis, a contract research organization and genome-scale diagnostics services company pioneering genome-guided medicine; A. Cecile Janssens, Ph.D., Professor at Emory University in Atlanta: and Uta Francke, M.D., Professor of Genetics and Pediatrics at Stanford School of Medicine, past President of the American Society of Human Genetics, and Senior Medical Director of the personal genomics company 23andMe. Dr. Green began by discussing the purposes of genetic testing: confirmation, diagnosis of mysterious diseases, risk profiling, and research. He also stressed context: medical versus consumer interest; clinical or research; pre-conception, pre-natal, pediatric or adult; various degrees of patient education; no results and anticipated results; and incidental findings.

Identification of Over 100 Schizophrenia-Associated SNPs and Certain Autism-Associated Rare Variants Reported at World Congress of Psychiatric Genetics in Boston

Today (Monday, October 21) was the last day of the five-day 2013 XXIst World Congress of Psychiatric Genetics in Boston and the tremendous success of the meeting and the enormous progress that has recently been made were remarked upon in a comment to BioQuick by Tom Insel (photo), M.D., Director of the National Institute of Mental Health (NIMH) since 2002. “This is a rapidly moving field. Five years ago, we had too few disease-associated variants. Now, perhaps, we have too many. At this meeting, we have heard reports of the identification of over 100 schizophrenia-associated SNPs, some overlapping with bipolar disorder. This is huge. In addition, we have heard about the identification of several rare variants associated with autism and intellectual disability. This is also huge,” Dr. Insel said. Many other new and exciting discoveries were described at the Congress and virtually all of the attendees would agree with Olli Pietilainen, Ph.D., from the Institute for Molecular Medicine at the University of Finland, and presenter of his group’s identification of a gene deletion associated with schizophrenia and intellectual disability, who commented to BioQuick that this was “absolutely the best of the many psychiatric congresses I have attended.” In keeping with the extremely high quality of the entire meeting. the final day’s opening plenary session featured lively presentations and a panel discussion involving four of the world leaders in their specialties, along with interactive audience participation on two questions--(1) how the field could continue the process of genetic discovery, and (2) what are the next steps to achieve biological understanding and translation of discoveries into the clinic.

October 20th

Autism Gene Studies, PsychChip Development, and Substance Abuse Genetics Featured in Saturday Session of World Congress of Psychiatric Genetics in Boston

Day 3 (Saturday, October 19) of the XXIst World Congress of Psychiatric Genetics, taking place in Boston, began with a spectacular plenary session featuring two world-class scientists as speakers—Christopher A. Walsh, M.D., Ph.D., Bullard Professor of Psychiatry at Harvard Medical School, Chief of the Division of Genetics at Children’s Hospital Boston, and Howard Hughes Medical Institute (HHMI) Investigator, and Kevin Eggan, Ph.D., Associate Professor in the Harvard University Department of Stem Cell Biology and Regenerative Medicine, an HHMI Investigator, and an acknowledged world leader in stem cell biology. Dr. Walsh described recent results in the world-wide and genome-wide hunt for inherited genes for autism spectrum disorders (ASDs), with an emphasis on studies looking for recessive genes in consanguineous families having members with ASDs. Dr. Eggan detailed the technical difficulties in working to create pure specific brain cell type populations from human embryonic stem cells, induced pluripotent stem (iPS) cells, or transfer factor treatment of fibroblasts. While not minimizing the problems, he described progress along the road to this goal and indicated the enormous potential that success in the technical challenges will have in the study of disease mechanisms, particularly in psychiatric disorders. Dr.Walsh said that autism has an incidence of 1-2 per 1,000, while ASDs have an incidence of 6 per 1,000. ASDs have comorbidities of 50-60% with cognitive impairment, 10-25% with regression, and 30% with seizures/epilepsy suggesting that they are developmental disorders associated with abnormal brain development, he added. ASDs are highly heritable, Dr. Walsh said, and yet genetic causes have been identified for only a small fraction of the totality of the disorders.

October 18th

Biomarkers for Suicidal Behavior, Stem Cells, and Epigenetics of Cocaine Addiction Highlight Second Day of World Congress of Psychiatric Genetics in Boston

On the second day (Friday, October 18) of the XXIst World Congress of Psychiatric Genetics meeting in Boston, Alexander Niculesca, M.D., Ph.D., Associate Professor in the Department of Psychiatry at the Indiana University School of Medicine, described his group’s ground-breaking work in identifying and validating blood biomarkers for suicidal behavior, in particular the identification of a panel of six markers whose levels in the blood can help predict the risk of future hospitalizations for suicide. Dr. Niculesca emphasized the significance of these findings by noting that one million people die each year from suicide and that someone commits suicide every 40 seconds. Furthermore, the omega-3 fatty acid DHA (docosahexaenoic acid), which is a major component of the human brain, cerebral cortex, skin, sperm, testicles, and retina, can be used in the diet to reduce the suicide risk in some at-risk patients. Consequently, the ability to identify patients at high risk of suicide through simple blood tests has the potential to save lives. The most powerful predictor of the six markers in the panel was the protein coded for by the gene SAT1. SAT1 codes for the rate-limiting enzyme in the catabolic pathway of polyamine metabolism. Dr. Niculesca’s work is an example of the use of a comprehensive convergent functional genomics approach to identify risk-related genes. The results of this work were published online on August 20, 2013 in an open-access article in Molecular Psychiatry. Following Dr. Niculescu’s talk, Rakesh Karmacharya, M.D., Ph.D., Assistant Professor of Psychiatry at Harvard Medical School, described the use of induced pluripotent stem (iPS) cells that were differentiated to neuronal cells in order to look for cellular signatures of schizophrenia and bi-polar disorder in patient-derived cells.

October 17th

World Congress of Psychiatric Genetics Opens in Boston

The XXIst World Congress of Psychiatric Genetics opened today (October 17, 2013), in Boston, Massachusetts, USA, with this year’s theme being “Redefining Mental Illnesses Through Genetics.” The five-day conference, organized by the International Society of Human Genetics (ISPG), is being attended by nearly 900 of the world’s leading research and clinical experts on psychiatric diseases such as autism, schizophrenia, and major depressive disorder. Approximately 300 of these scientists have come from outside the United States. The scientists are discussing the latest developments in their fast-moving field and describing their visions of a brighter future that their work will hopefully provide, in terms of testing, treatments, and possibly even cures. On this opening day, Francis McMahon, M.D., a principal investigator at the National Institute of Mental Health, and president of the ISPG, commented to BioQuick that “the Congress program, coupled with the number and caliber of the attendees, is indicative of the steep curve of discovery in the field. With increases in sample sizes, advances in technology, and all the bright people involved, it is very likely that we will make discoveries in the next decade that will help patients and also help psychiatrists deliver better treatments.” The keynote address for the Congress was delivered by George Church, Ph.D., professor of genetics at Harvard Medical School, director of, and universally acknowledged technical wizard who has invented numerous sequencing technologies over the years and been involved in the launches of numerous biotech companies. He is also one of six scientists who proposed the new BRAIN Initiative, which was announced on April 2, 2013 by President Obama, and intends to map the activity of every neuron in the human brain. Dr.