title: Calpain 10 and genetics of type 2 diabetes.
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.
authors.affiliation: University of Chicago, Department of Human Genetics, 507H CLSC, 920 E. 58th Street, Chicago, IL 60637, USA. ncox@genetics.uchicago.edu
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
mesh_terms: D002154:Calpain / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans
chemical_list: D002154:Calpain; C415197:calpain 10