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Jay Shendure; Future Challenges and Functional Consequences. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
Presentation Description :
The sequencing of individual human genomes may soon be routine in certain clinical contexts - for example, to diagnose suspected Mendelian disorders. However, even as the costs plummet to $1,000 or less, the value of a "personal genome" will remain highly constrained by the poor interpretability of individual genetic variants. For example, although BRCA1 and BRCA2 are clinically actionable when loss-of-function mutations are present, the result returned to patients is often still "variant of uncertain significance.” This challenge will profoundly deepen as clinical sequencing accelerates and as the list of clinically actionable genes grows. To address this, we are developing novel approaches for experimentally measuring the functional consequences of such "variants of uncertain significance" that exploit massively parallel technologies for nucleic acid synthesis and sequencing towards a new paradigm for dissecting function at saturating resolution. The application of this paradigm will yield experimentally grounded predictions for the functional consequences of all possible single residue variants, thereby informing the interpretation of variants newly observed in patients.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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