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Hood Keynote Highlights Conference on Future of Genomic Medicine

In the keynote address to 300 attendees at the Future of Genomic Medicine III conference in La Jolla, California (March 5-6, 2010), Dr. Leroy Hood, President of the Institute for Systems Biology, sketched his optimistic vision of the future of personalized DNA-based medicine, and predicted that within five years it will be possible to sequence an entire human genome in under an hour for a cost of $500 or less. He emphasized the importance of taking a systems approach to biological investigations and described how such an approach had been applied to the analysis of prion disease in a mouse model. Dr. Hood also outlined the first-ever full genome sequencing of a complete family of two children and both parents, in which both children had inherited the same two rare recessive genetic diseases (Miller’s syndrome and primary ciliary dyskinesia), but both parents were unaffected. The analysis of the four complete sequences revealed the two disease genes that were inherited by both affected children. Dr. Hood noted that the ability to compare all four related sequences allowed for a significant increase in sequencing accuracy. Dr. Hood also envisioned a future of individual patients surrounded by clouds of data points that might prove key to their individual diagnoses and therapies, and he emphasized that biology is an informational science. He noted that the management and interpretation of data will be crucial going forward. He said that a critical goal for medical genetic tests is that they be both predictive and actionable. Dr. Hood was just one of many luminaries who took to the podium at this year’s conference, hosted by the Scripps Translational Science Institute and the J. Craig Venter Institute, and sponsored by a number of major biotech and pharmaceutical companies.

The kickoff presentation was delivered by Greg Lucier, Chairman and CEO of Life Technologies Corporation, maker of the SOLiD next-generation sequencing instrument. With some spectacular visuals, Mr. Lucier outlined a bright future of personalized medicine enabled by key technological advances. He particularly noted the need for genetics education of physicians and the general populace, and highlighted the importance of adding genomic imaging to other sophisticated imaging techniques, such as CAT scans and MRIs, that have already revolutionized the practice of medicine.

Dr. Elaine Mardis, Co-Director of the Genome Center at Washington Unversity, described her group’s ground-breaking work in sequencing cancer genomes, specifically the genome of acute myeloid leukemia (AML), and commented on her group’s efforts to identify cancer-specific mutations. Later in the meeting, Dr. Mardis was presented with the conference’s annual achievement award for her team’s accomplishment in sequencing the first human cancer genome.

Dr. Deborah Nickerson, Professor of Genome Sciences at the University of Washington, described some of her pioneering work in exome sequencing and indicated how she is applying this approach to identifying novel genes for rare Mendelian diseases.

Dr. Stephen Kingsmore, CEO of the National Center for Genomic Resources, in Albuquerque, New Mexico, described how his center has been employing the new sequencing technologies to undertake high-resolution, individual sequencing and inter-individual genome sequence comparisons. Two studies were highlighted. In one, the sequencing of a Korean individual revealed 3.45 million SNPs, including over 10,000 non-synonymous SNPs and over 170,000 indels. SNP and indel densities were found to be strongly correlated genome-wide. Very conservative criteria yielded 315 copy number variants (CNVs), totaling 9.4 million bases.

In the second study, Dr. Kingsmore’s group performed high-resolution sequencing of a monozygotic twin pair that was discordant for multiple sclerosis. In addition, the group obtained transcriptome and epigenetic sequences from the CD4+ lymphocytes for three MS-discordant monozygotic twin pairs. Analysis of the results failed to reveal any evidence for genetic, epigenetic, or transcriptome differences in the twin pairs that would explain their discordance for MS.

Dr. Joe Nadeau, Chair of Genetics at Case Western Reserve University, described a fascinating mouse model in which inheritance was passed on not from parents, but from grandparents or great-grandparents.

Dr. Doug Wallace, the renowned mitochondria expert formerly at Emory University and now at the University of California-Irvine, gave an energized presentation on the powers of the mitochondria and the relationship between these energy-producing organelles and the aging process. Dr. Wallace noted that mitochondria are, in fact, major determinants of health and disease in humans and that this owes to five characteristics of mitochondria--they generate energy; they are a major regulator of oxidation-reduction reactions; they are a major source of reactive oxygen species (oxidizing agents); they are a major regulator of calcium; and they are a major regulator of programmed cell death or apoptosis.

Interestingly, Dr. Wallace noted that of the thousands of genes present originally in mitochondria, all but 13 have, over evolutionary time, been transferred out of the mitochondria to the chromosomes in the nucleus. The function of the 13 remaining genes is no surprise, he said, as the proteins they code for form the capacitor for the mitochondria. Each protein has to be balanced with the other or the capacitor is destroyed and the cell runs out of energy.

Dr. Wallace also noted the high frequency of mutations in mitochondrial DNA and pointed out that, as these mutations accumulate, energy production declines, until it falls below the minimal energy requirements for a particular organ—“the equivalent of a metropolitan brown-out”—“and you begin to get energetic failure, symptoms, and ultimately disease.” The organs that most rely on energy production include the brain, heart, muscle, and kidneys—all of which are involved in the aging process, he said.

Dr. Thomas Perls and Dr. Paola Sebastiani, both of Boston University, gave a tag-team presentation on their work with centenarians. Among the goals of their research are the discovery of genetic modifiers of human lifespan and healthspan, and the translation of these findings into public health interventions. Dr. Perls is Director of the New England Centenarian Study which has, to date, worked with over 1,600 centenarians. Dr. Sebastiani is a Professor in the Department of Biostatistic in the School of Public Health at Boston University. Their presentation focused on genome-wide association studies to identify genetic modifiers of human exceptional longevity.

Dr. Nil Barzilai, Director of the Institute for Aging Research at Albert Einstein College of Medicine, spoke on the genomics of aging, and Dr. Eric Topol, Director of the Scripps Translational Science Institute, focused on the genetics of healthy aging, drawing an interesting distinction between the “wellderly” and the “illderly” in aging populations.

Numerous other top-flight speakers kept the audience enthralled with the progress and prospects of genomic medicine.

The conference was superbly organized and orchestrated by Dr. Topol and Dr. Robert Strausberg, Director for Collaborative Sciences at the Ludwig Institute for Cancer Research, Ltd., in New York.

Major sponsors of the event included Life Technologies, Sanofi-Aventis, The Medicines Company, Illumina, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Gen-Probe, Lilly, Quest Diagnostics, MedImpact Healthcare Systems, AltheaDx, Complete Genomics, Cypress Biosciences, Genomic Health, Rain Dance Technologies, and CardioDx.