title: Mapping genes for autoimmunity in humans: type 1 diabetes as a model.
abstract: Type 1 diabetes (T1D) arises from autoimmune destruction of the beta cells of the pancreas leading to a complete dependence on exogenous insulin for survival. Like many autoimmune disorders, the etiology of T1D is complex, resulting from the action of multiple genes and environmental factors. Identification of genes that contribute to T1D susceptibility should improve disease prediction and contribute to the understanding of the underlying pathology of the disorder. Two regions of the human genome, the human leukocyte antigen (HLA) region and the insulin gene region are generally thought to contain susceptibility loci for T1D. Although additional putative T1D loci have been reported, the supporting evidence has often been of modest significance and findings have displayed poor reproducibility across multiple studies. This review summarizes the current state of genetic linkage and association studies in T1D and suggests future directions. We argue that much of the difficulty in mapping T1D susceptibility loci has resulted from inadequate sample sizes and we illustrate the substantial gains in power that can be achieved by pooling data across studies. These findings suggest that substantial progress toward the identification of susceptibility genes in T1D and other genetically complex disorders may be achieved through increased collaboration and consortium mapping efforts.
authors.affiliation: Molecular Genetics Program, Virginia Mason Research Center, Seattle, WA 98101, USA.
authors.forename: Suna
authors.initials: S
authors.lastname: Onengut-Gumuscu
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
mesh_terms: D015551:Autoimmunity / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics; D018448:Models, Immunological
chemical_list: D006680:HLA Antigens; D007328:Insulin