Abstract
Positional cloning studies conducted on a region of chromosome 2q providing evidence for linkage to type 2 diabetes implicated genetic variation at the calpain-10 gene (CAPN10) in susceptibility to type 2 diabetes. The variants identified in these studies are located in introns, rather than in coding sequence. It was proposed that the cumulative effects of a combination of variants, rather than variation at a single site, increase the risk of type 2 diabetes. Confirmation of the hypothesis that non-coding sequence variation in CAPN10 affects susceptibility to type 2 diabetes has implications for how we search for susceptibility variants and interpret results of positional cloning studies for complex disorders, and suggests a new pathway in glucose homeostasis. We review the results of follow-up studies on the CAPN10 finding, and consider the issues inherent in conclusively establishing that particular genetic variation affects a complex phenotype.
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Cox, N.J. Calpain 10 and genetics of type 2 diabetes. Curr Diab Rep 2, 186–190 (2002). https://doi.org/10.1007/s11892-002-0079-1
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DOI: https://doi.org/10.1007/s11892-002-0079-1