September 19, 2014, 1 p.m. to 2 p.m. James Lupski, MD, PhD, Cullen Endowed Chair in Molecular Genetics, Professor, Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, Member, Institute of Medicine of the National Academies Virginia Tech Carilion Research Institute Following the “finished” euchromatic, haploid human reference genome sequence, clinical implementation of genome-wide assays for genomic disorder associated copy number variants (CNVs) has demonstrated the tremendous utility of capturing rare, unique, and often de novo genetic variation for establishing a molecular etiological diagnosis. The rapid development of novel, faster, and cheaper ‘next generation’ massively parallel DNA sequencing technologies is making possible the era of personal human genomics. Personal diploid human genome sequences have been generated and have contributed to better understanding of rare variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide (SNV) to structural variants including CNV. Translation of genome-scale variation into medically useful information is, however, in its infancy. In his presentation, Dr. Lupski will summarize the initial steps undertaken in clinical implementation of personal genome information, and describe the application of whole-genome arrays and exome sequencing to identify the rare genetic susceptibility variants that can contribute to disease and to suggest adjuvant therapies. Better analysis tools, particularly for determining CNV from sequence and a deeper understanding of the biology of our genome and mechanisms for mutagenesis are necessary in order to continue to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. The function of the majority of human genes remains unknown; interpretation of noncoding variation without a ‘genetic code’ to translate the information is a challenge; Encode is not the Rosetta stone for noncoding sequence. Current personal genome research and clinical practice suggest tremendous utility for this genomic information. Such information may eventually become an instrument of common medical practice, an adjuvant to the family history, providing information that assists in the formulation of a differential diagnosis.

• published: 18 Sep 2014
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