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William E. Balch; An Emergent Paradigm for Vision Research: Proteostasis, Variation and Precision Management of Human Disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1.
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Presentation Description :
This keynote will address the problem of defining the impact of human variation responsible for protein misfolding, as seen in inherited vision diseases (e.g., macular degeneration, retinopathies, retinitis pigmentosa, glaucoma, cataracts, etc.), which pose a major challenge to application of human genome sequencing efforts where thousands of synonymous and non-synonymous SNPs alter the genotype of each one of us to engender our personalized biologies responsible for both health and disease. Variation contributing to vision loss challenge management of the proteome by proteostasis, the central chaperome system controlling the biosynthesis, maintenance and degradation of the protein fold. We apply new genomic profiling approaches to capture sequence variation in the population in the context of the phenotypic features that define fold function, enabling the generation of landscapes that predict the logic linking sequence, function, and structure relationships at atomic resolution for the individual. Landscape design features reveal an unanticipated level of folding dynamics that specify differential function of the polypeptide in a cell, tissue and individual specific manner. Variation in the population emphasizes the adaptive and differential role of proteostasis in the management of diversity in the genotype to phenotype transformation, lending credence to a high definition* genomics-based precision medicine approach to vision science at the bench and bedside. (*Torkamani, A., Andersen, K. G., Steinhubl, S. R. & Topol, E. J. High-Definition Medicine. (2017) Cell 170, 828-843, doi:10.1016 / j.cell.2017.08.007 (2017)).
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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