title: HLA disease associations: models for the study of complex human genetic disorders.
abstract: The genes of the human leukocyte antigen (HLA) region, the major histocompatibility complex (MHC) of humans, control a variety of functions involved in immune response and influence susceptibility to over 40 diseases. Theoretical studies in the development of models to determine the modes of inheritance of the HLA-associated diseases have led to a better understanding of the inheritance patterns in insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, hemochromatosis, celiac disease, and others. It is now clear that many of the HLA-associated diseases involve heterogeneity in their HLA components, as well as non-HLA genetic factors. This review is presented using HLA-associated diseases, and in particular IDDM, as the example of interest, but the observations and techniques presented have direct relevance to the study of all human diseases with a complex genetic component. Three methods for localizing disease-predisposing genes are presented: (1) association studies, including population, family, and relative predispositional effects, (2) affected sib pair and other affected-relative methods, and (3) lod score analysis. A variety of complementary methods for studying the mode(s) of inheritance of the alleles at the disease-predisposing locus and for identifying the alleles and amino acids directly involved in the disease process also are presented.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley 94720-3140, USA.
authors.forename: G
authors.initials: G
authors.lastname: Thomson
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D005826:Genetics, Medical / Q000379:methods*; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D010375:Pedigree
chemical_list: D006680:HLA Antigens