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Identification and Investigation of Mucin 1‐Mediated Kidney Disease
Author(s) -
Schuler Bryce,
Tsaih ShringWern,
Worthey Elizabeth,
Kirby Andrew,
Stevens Christine,
Daly Mark,
Jacob Howard
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.663.1
Subject(s) - disease , biology , genomics , population , phenotype , genetics , kidney disease , transplantation , genome , computational biology , bioinformatics , medicine , gene , pathology , endocrinology , environmental health
Establishing a causal link between genomic variation and pathology is the foundation of the successful application of genomics to clinical medicine. Whole genome sequencing (WGS) increases the resolution with which we can investigate the genome, but this increased resolution leads to an increase in the number of potentially damaging or disease causing variants identified. Consequently, WGS in the analysis of disease requires both bioinformatics approaches for efficient prioritization of variants as well as experimental evidence that demonstrates that the variant alters the function of the protein which directly contributes to the development of the disease phenotype(s). We have identified a family with an autosomal dominant chronic tubulointerstitial nephritis that presents insidiously between 20 and 60 years of age, leads to end stage renal disease, and subsequently requires dialysis and transplantation. By utilizing a WGS approach in affected members of this family, literature queries, and targeted gene analyses, we were able to identify a single base insertion in mucin 1 (MUC1) that segregated with the disease in this family, was absent in the general population, and was bioinformatically interesting. We are utilizing a mutant Muc1 rat model in an effort to confirm that MUC1‐dysfunction is causative in this phenotype, to more completely characterize this disease process, and to investigate potential treatment strategies with the hope that subsequent findings can, at least in part, be directly applied to patient care. Funding was provided by the NIH (award 5T32HL007852‐17) and an extramural donation.