Multispecies, Integrative GWAS for Focal Segmental Glomerulosclerosis
Technical Report,15 Aug 2016,14 Aug 2017
Trusees Of Columbia University New York United States
Pagination or Media Count:
The goal of this project are to identify genetic determinants of focal segmental glomerulosclerosis FSGS using genomewide association studies in mouse strains. We have shown that the development nephropathy in the HIV-1 transgenic miceTgFVB is highly strain dependent. Linkage mapping in murine crosses have shown that thereare at least 4 FSGS susceptibility loci among inbred strains. Furthermore, F1 hybrids between TgFVB and other inbred strains show highly variable penetrance of nephropathy, indicating the feasibility of mapping genes using F1 hybrids for association mapping. In the past funding period, we have generated 305 F1 hybrids between TgFVBand 12 inbred strains and have determined variable susceptibility to kidney disease based on genetic background, with C57Bl6J, AJ, DBA1J, NZOHILtJ and CBAJ mice showing highest prevalence of injury as measured by proteinuria, and urinary NGAL levels. By performing serial analysis of proteinuria, we have also determined the optimal timepoint for assessment of kidney disease in the f1 progeny. Our goal is continue breeding the F1 cohort using total of 30 inbred strains. We will continue to characterize phenotypes based on proteinuria, UNGAL and histopathology. Once the cohort has been generated, we will perform a GWAS to detect susceptibility loci for FSGS and compare results to the ongoing GWAS in humans.
- Medicine and Medical Research