Editors' ChoiceHuman Genetics

The Genome Speaks

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Science Translational Medicine  19 May 2010:
Vol. 2, Issue 32, pp. 32ec79
DOI: 10.1126/scitranslmed.3001276

The publication of the initial draft of the human genome required a multinational decade-long effort at a cost of close to 3 billion dollars. In the next 2 to 3 years, the cost to sequence a human genome will drop below 1000 dollars and will enable large-scale sequencing of hundreds of thousands of individuals. Now, Ashley and colleagues give us a sneak peek into our genomic future by extensively annotating the whole genome of a 40-year-old healthy male Stanford University research scientist. Over 60 pharmacogenetic variants with an immediate impact on drug efficacy and toxicity were detected. These included variants conferring a heightened response to aspirin and the commonly used blood thinner warfarin; a reduced response to the antiplatelet agent clopidogrel and the antidiabetic agent metformin; and a normal response to statins—the most commonly prescribed drugs in the world. Remarkably, the patient also harbored variants in the lipoprotein (a), myosin-binding protein C, and desmoplakin genes that place him at an increased risk for coronary artery disease and sudden cardiac death, which is consistent with his family history. Variants conferring enhanced susceptibility to obesity, diabetes, and a number of additional common and rare diseases were also present.

Together, these findings substantially bolster arguments for using genomic information in order to personalize medicine. However, several important variables require addressing before we can systematically apply whole-genome data in routine clinical practice. First, susceptibility variants need to be evaluated in appropriately designed prospective studies that incorporate important lifestyle and environmental factors. Only then can we truly establish the genetic contribution to disease risk. Second, as more individuals are sequenced, more rare and common disease–causing variants will emerge, requiring an efficient system that is continuously updating and vetting all newly generated disease loci. Third, a sufficient number of adequately trained physicians and genetic counselors who understand and can accurately convey the full scope of a patient’s genetic risk profile need to be readily available. Going forward, these challenges will certainly be overcome in the years ahead. However, in the interim, rest assured that the genome will continue to speak to us by illuminating previously unknown biologic pathways involved in disease susceptibility and drug response.

E. A. Ashley et al., Clinical assessment incorporating a personal genome. Lancet 375, 1525–1535 (2010). [Abstract]

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