Genetic analysis of IDDM: summary of GAW5 IDDM results - PubMed (original) (raw)

Review

Genetic analysis of IDDM: summary of GAW5 IDDM results

R S Spielman et al. Genet Epidemiol. 1989.

Abstract

This paper summarizes the analyses by participants in the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5). The data were obtained from 94 families with two or more IDDM sibs. Topics treated in the Workshop analysis included the following: methods for detecting associations and linkage, the contribution by HLA-linked and -unlinked loci to IDDM susceptibility, the role of subtypes of the serologically defined HLA specificities, the implications of associated diseases other than IDDM in the families, the significance of antibodies to Coxsackie viruses, and of autoantibodies to pancreatic islet cells and insulin, and the use of genetic models to analyze the inheritance of IDDM. There was agreement that an explanation for the data on multiplex IDDM families must include the following features: 1) There is a susceptibility locus (or loci) in the HLA region. 2) The HLA-linked factor(s) are more complex than a single locus with one disease and one nondisease allele. 3) There is additional familial correlation beyond that explained by HLA-linked susceptibility, which may be genetic and/or environmental. With regard to the third feature, IDDM-GAW5 included data on variation in Gm haplotypes and at the insulin gene, two regions unlinked to HLA. However, there was no direct evidence (i.e., from marker segregation) that the additional factor, if genetic, is linked to either Gm or the insulin gene. Nevertheless, a significant difference was found between "diabetic" and "control" insulin genes with respect to frequency of class 1 alleles for the 5' flanking polymorphism, strongly suggesting linkage.

PubMed Disclaimer

Cited by

Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate.
Feng H, Sassani R, Bartlett SP, Lee A, Hecht JT, Malcolm S, Winter RM, Vintiner GM, Buetow KH, Gasser DL. Feng H, et al. Am J Hum Genet. 1994 Nov;55(5):932-6. Am J Hum Genet. 1994. PMID: 7977355 Free PMC article.
T cell receptor haplotypes in families of patients with insulin-dependent diabetes mellitus.
Kelly H, Garlepp MJ. Kelly H, et al. Clin Exp Immunol. 1993 Feb;91(2):226-31. doi: 10.1111/j.1365-2249.1993.tb05887.x. Clin Exp Immunol. 1993. PMID: 8094039 Free PMC article.
Viral antibody titers, immunogenetic markers, and their interrelations in multiple sclerosis patients and controls.
Alpérovitch A, Berr C, Cambon-Thomsen A, Puel J, Dugoujon JM, Ruidavets JB, Clanet M. Alpérovitch A, et al. Hum Immunol. 1991 Jun;31(2):94-9. doi: 10.1016/0198-8859(91)90011-w. Hum Immunol. 1991. PMID: 2066275 Free PMC article.
The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families.
Noble JA, Valdes AM, Cook M, Klitz W, Thomson G, Erlich HA. Noble JA, et al. Am J Hum Genet. 1996 Nov;59(5):1134-48. Am J Hum Genet. 1996. PMID: 8900244 Free PMC article.
Genetic analysis of susceptibility to type 1 diabetes.
Todd JA. Todd JA. Springer Semin Immunopathol. 1992;14(1):33-58. doi: 10.1007/BF00197131. Springer Semin Immunopathol. 1992. PMID: 1440197 Review. No abstract available.

Genetic analysis of IDDM: summary of GAW5 IDDM results - PubMed (original) (raw)