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Awards, Newborn Screening, and Futuristic Presentations Highlight Last Day of ASHG Annual Meeting

The breakthrough-loaded 2013 annual meeting of the American Society of Human Genetics (ASHG) ended its five-day run in Boston with an awards session, followed by concurrent research presentation sessions, and ending with three riveting presentations on the future of genetics and systems biology by three world-leading researchers. The morning started with the presentation of the ASHG Victor A. McKusick Leadership Award presently jointly to Rochelle Hirschorn, M.D., and her husband, Kurt Hirschorn, M.D. The McKusick award honors the legendary Victor McKusick, M.D., who is often referred to as the “Father of Medical Genetics,” and his far-reaching and visionary contributions to genetics. Recipients are chosen for their enduring vision and leadership to ensure that human genetics will flourish and be successfully assimilated into the broader context of science, medicine, and health. In a moving moment, the award recipients were introduced by their son, Joel, M.D., Ph.D., from the Department of Genetics at Harvard Medical School. Dr. Rochelle Hirschorn was the Chief of Medical Genetics at New York University’s Langone Medical Center for 24 years. Her major discoveries include clarifying the sequence of acid alpha glucosidase and most of its defects in Pompe disease, and delineating the genetic structure and pathophysiology of adenosine deaminase (ADA ) deficiency, an autosomal recessive metabolic disorder that causes immunodeficiency. She also described the phenomenon of reverse mutations as a cause of “self-cure” in ADA deficiency patients and predicted the utility of gene therapy for ADA deficiency. She was also in the forefront of promoting the equality of women and was the first female member of the Interurban Club, founded by famous physician William Osler and she was later elected the Club’s first female president. Kurt Hirschorn, M.D., was Chief of the Division of Genetics at Mount Sinai School of Medicine (MSSM) for eight years and Chief of Pediatrics at MSSM for 18 years. His chief scientific achievements include the discovery, characterization, and application of the mixed-lymphocyte reaction and the early and sustained use of cytogenetics to discover and describe multiple human chromosome disorders, including the Wolf-Hirschorn syndrome, also called 4p-syndrome. At the end of his address to the large audience, the 87-year-old Dr. Kurt Hirschorn mentioned the joy that his wonderful family of wife Rochelle and three children had given him, and concluded, “All in all, a good life for a refugee kid who came here in 1940.” The Hirschorns have been married for 60 years and when their award was announced, they received a standing ovation from the audience. Next came the Cotterman Awards that are presented for the two articles published in the American Journal of Human Genetics (AJHG) in the previous year that best represent outstanding contributions to the field of human genetics. The awards, consisting of a $1,000 monetary award and a certificate are given for two such papers on which the first author is a pre- or post-doctoral fellow and also a member of the ASHG, This year the awards were presented by AJHG editor David Nelson, Ph.D., Professor of Molecular and Human Genetics, Baylor College of Medicine to Natalie Powers, Ph.D, for her June 6, 2013 article “Alleles of a Polymorphic ETV6 Binding Site in DCDC2 Confer Risk of Reading and Language Impairment” ( published while she was in the Department of Genetics at Yale University; and to Pier Francisco Palamara, Ph.D. candidate in the Computer Science Department at Columbia University for his November 2, 2012 article “Length Distribution of Identity by Descent Reveals Fine-Scale Demographic History” ( Next came the ASHG Charles J. Epstein Awards honoring excellence in research conducted by predoctoral and postdoctoral trainees, include genetic counseling trainees. 63 semifinalists were selected, from whom the six winners were selected and received $1,000 in addition to the monetary awards they had previously received their earlier selections to the larger groups. The awards were presented by Christopher E. Pearson, Ph.D., Senior Scientist and Associate Professor in Genetics and Genome Biology at The Hospital for Sick Children in Toronto, Canada. The winners were three predoctoral candidates: Andrew.B. Stergachis, University of Washington; Juan Calderon, Johns Hopkins; and Iain Mathieson, Wellcome Trust Centre for Human Genetics; and three postdoctoral trainees: A. –K. Arndt, C.R. French, and S. Gopalakrishnan. These award presentations were followed by the awarding of the ASHG Curt Stern Award, named in honor of the late pioneering geneticist Curt Stern, Ph.D., and which recognizes researchers who have made significant scientific contributions during the past decade. This year’s award was presented to John V. Moran, Ph.D., Professor of Human Genetics and Professor of Internal Medicine in the Department of Internal Medicine at the University of Michigan for his work on mobile DNA or “jumping genes.” Dr. Moran was introduced by his former mentor, the legendary scientist, Haig Kazazian, M.D., Professor of Human Genetics at Johns Hopkins, who has worked on the biology of LINE-1 (L1) retrotranspons for 22 years. Dr. Kazazian said that when Dr. Moran first came to his lab, he designed a complicated experiment that Dr.Kazazian believed had little chance of working and he was amazed when it actually worked the first time. “John’s experiments always seemed to work,” Dr. Kazazian said. Dr. Moran’s experiments have shown that retrotranspons affect genome evolution in many ways, Dr.Kazazian He added that Dr. Moran’s experiments typically incorporate every possible control and that he is “loaded with ideas, many of them really good.” He did note one egregious fault, namely that Dr. Moran is a diehard fan of the New York Yankees, a fact that goes over particularly badly in the city of Boston. He praised Dr. Moran’s devotion to his wife and three children and ended by saying that he was “an impeccable scientist.” Dr. Moran came to the podium, thanked Dr. Kazazian for his kind words, and accepted the beautiful glass plaque and monetary award associated with the award. He then briefly described some of his seminal research work and the arc of his career path. He noted that he studies LINE-1 retrotranspons and that these mobile elements are now known to constitue one billion bases of human DNA and to affect the mobility of Alu elements. He suggested that study of these L1 elements is necessary to understand some of the forces that have shaped the human genome. He noted that he first became interested in this research focus after reading a Cell article by Jef Boeke on Ty1 elements in yeast. He essentially “fell in love with mobile elements,” he said. He also cited Tom Cech’s work on catalytic RNAs as highly influential. He also noted the influence of Dr. Kazazian’s 1988 paper in Science on the “Isolation of an Active Transposable Element.” After that he went on to work with Dr. Kazazian, whom his lab researchers called the “Big Guy,” at Johns Hopkins, and followed him to the University of Pennsylvania. Dr. Moran noted that Dr. Kazazian later moved back to Johns Hopkins, demonstrating some of the mobility characteristics of the elements he studied. In 1996, Dr. Moran and colleagues published the details of a powerful assay for L1 transpostion in Cell. Seeking to end his own peripatetic research travels and to secure gainful employment for his growing family, Dr. Moran took a position at the University of Michigan Medical School, where he remains today. He remarked on the pleasure that his family—wife Robin and three children—gives him, and ended by saying that he would rather live a life that “was hectic, rather than boring.” The ASHG press release announcing this year’s Curt Stern Award noted that Dr. Moran is a Howard Hughes Medical Institute Investigator, who has been a leader in research on genome instability and the biology of DNA sequences that can change their position in the genome, creating or reversing mutations and altering the genome’s size. Among his accomplishments is the discovery that processed pseudogenes are formed in the genome by the reverse transcriptase enzyme for the mobile DNA element referred to as L1. He developed the cell culture assay used in this research. His finding that the L1 insertion can lead to deletions in the genome has been confirmed by human genome analysis as well as numerous other studies, demonstrating the importance of retrotransposition in shaping the human genome through evolutionary time, and showing that these L1 insertions occur much more frequently than previously thought. The Curt Stern Award also recognizes Dr. Moran’s mentorship of graduate students and postdoctoral researchers as well as his stalwart support of and service to ASHG. At the end of the awards session, the ASHG held the meeting’s last set of concurrent research symposia. One of the many highlights of the seven final symposia was the session entitled “Whole Genome Sequencing for Every Baby? Where Diagnostics and Screening Applications Collide.” This highly informative and provocative session was organized by the Genetic Alliance (, a Washington, D.C.-based organization that is devoted to promoting optimum health care for people suffering from genetic disorders. The Genetic Alliance runs Baby's First Test (, which is the nation's newborn screening resource center. The ASHG session was moderated by James O’Leary and Natasha Bonhomme, both of the Genetic Alliance. The first speaker was Olaf Bodamer, M.D., Ph.D., Clinical Professor in the Department of Human Genetics and Director of the Division of Clinical and Translational Genetics at the John P. Hussman Institute of Human Genomics at the University of Miami. He began by noting that the first newborn screening test was the test for phenylketonuria (PKU) developed over 50 years ago by Dr. Robert Guthrie. This tests indicates whether the baby has the enzyme needed to metabolize the amino acid phenylalanine. This deficiency can lead to severe brain damage if not addressed promptly with dietary measures that severely restrict the intake of phenyalanine. Dr. Bodamer cited a number of problems that would be posed by genome-wide sequencing of newborns. First, there is a lack of evidence for most conditions; the definitions of conditions have not been adequately developed; results of unknown significance pose a major challenge. He described a number of requirements for technology-based changes in newborn screening and indicated how far along we currently are in achieving these goals. He said the test must be doable on filter cards (+++); must have high-throughput capability (-); must have multiplex capability (+++); must have adequate turnaround time (+/-); must have high sensitivity and specificity (++); must have stable automated analytic platform (+/-): and finally, must have a low cost per sample (--), i.e., in the $80-$100 per sample. He highlighted a fourth-generation exome sequencing system from Gnu Bio as including a DNA extraction protocol that allows DNA to obtained in under three hours versus the typical 24-48 hours typically afforded by other systems. He noted that at the University of Miami they are working on a newborn screening project and have already shown that relatively low DNA input can be effectively used for whole-exome sequencing. In conclusion, however, he stated his opinion that genome technology is not yet ready for use in newborn screening due to lack of scalability, lack of high throughput, and high cost per sample. He also noted the recent NIH funding for Genomic Sequencing and Newborn Screening Disorders research program, which has already awarded grants of $5 million each to four grantees and will be funded at $25 million over five years as funds are made available. The next speaker was Jeffrey Botkin, M.D., M.P.H.., Chief of Medical Ethics at University of Utah Health Care. He launched his talk by asking the question, “what are we testing for?” and noting that sequencing is “a tool that is out there.” He noted that despite the advances in genome sequencing technology, the best test for cystic fibrosis remains the long-used sweat test. He said that, although the use of sequencing would seem to be a no-brainer, it actually poses highly complex issues. One of the dicta of newborn screening is that requires clear evidence of benefit to the child. He emphasized the problem of “incidental findings” that whole genome or whole exome sequencing engenders—findings for which there is no treatment and no infrastructure to manage. He noted that whole genome and whole exome sequencing generate a substantial number of false positives and identify multiple variants of unknown significance. He commented that, perhaps surprisingly, people actually tend to prefer hearing bad news than uncertain information. He concluded by stating that whole genome or whole exome sequencing cannot now be justified under a state mandate. Use of these technologies does make “enormous sense” in the research setting, he said. Next to speak was Aaron Goldenberg, Ph.D., M.P.H., Assistant Director of the Center for Genetic Research Ethics and Law at Case Western University. He presented polling data seeking to determine the level of parental interest in the use of whole genome screening of newborns. In one poll, parents were asked if they would be interested in whole genome sequencing tests if they migh affect the health of their child. The results showed that 36% were “definitely interested,” 38% were “somewhat interested,” 18% were “not interested,” and 8% were “definitely not interested.” Factors influencing the parents’ response included accuracy of the test, ability to preventing or decreasing child’s chance of developing a disease, privacy, and possibility of use in discrimination. Dr. Goldenberg also discussed the use of genomics as a mandatory secondary screen versus as an optional choice for parents. The final speaker was Yvonne Bombard, Ph.D., Research Fellow at Memorial Sloan-Kettering Cancer Center and Assistant Professor at the University of Toronto. She emphasized that the untargeted use of genome sequencing in newborn screening might challenge the public support upon which such programs rely. As others had, she noted the problem of genome sequencing providing large amounts of additional information that is difficult to deal with. She mentioned that redoing part of the newborn screening approach would potentially challenge the moral authority that newborn screening programs rely upon to ensure the payment of benefits. In addition, the cost of the testing would surely influence public engagement. The 2013 ASHG annual meeting closed with stimulating futuristic addresses by three of world’s leading scientists—Marc Vidal, Ph.D., Dana-Farber Cancer Institute and the Department of Genetics, Harvard Medical School; Aviv Regev, Ph.D., a computational biologist at the Broad Institute of MIT and Harvard, Associate Professor in the Department of Biology at MIT and an Early Career Scientist at the Howard Hughes Medical Institute; and Garry Nolan, Ph.D., Rachford and Carlota A. Harris Professor in the Department of Microbiology and Immunology, Stanford University School of Medicine. The distinguished speakers were introduced by Andrew G. Clark, Professor of Population Genetics in the Department of Molecular Biology and Genetics at Cornell University. The illustrious speakers were addressing the topic of systems biology and its application to medical genetics and they did not disappoint. Dr. Vidal gave a scintillating presentation his group’s work on the “interactome,” that is, the sum of all the molecular interactions in the human body, and how perturbations of these network interactions may have impact on human disease. He said there is a biophysical interactome network consisting of interactions such as protein-protein, DNA-transfer factors, miRNA-targets, and RNA-protein. There is also a functional interactome network consisting of genes (nodes) and genetic interactions (edges). He noted that humans have approximately 20,000 proteins that imply 200,000,000 combinations of physical protein interactions. He emphasized the need to establish an interactome reference map that would account for these 200 million possible combinations. He used the term “edgotyping” to describe the description of the gene interactions in the interactome and suggested that different diseases result from different “edgotypes.” He noted that most isoforms actually have vastly different interactional profiles. Dr. Regev followed with a compelling presentation on the challenge of moving from components to circuits and the need to actually explain what is going on in “”hairballs” of interactions that are generated in protein-protein interaction maps. In her talk, she focused on studies done with dendritic cells, the “sentinel cells,” of the immune system. Her work has shown that there is a set of “early responder” dendritic cells that can reduce the anti-viral response and increase the inflammatory response when challenged with LPS. Dr. Nolan closed the meeting with a riveting discussion of determining a definable “structure” for the immune system and cancers at the single cell level. Attendees are now eagerly looking forward to the 2014 ASHG annual meeting, which will be held in San Diego, California, October 18-22, 2014. [The Genetic Alliance] [NIH Grants for Newborn Screening Research] [ASHG Annual Meeting 2013] [ASHG Annual Meeting 2014] [ASHG]