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Genetic analysis of IDDM: Summary of GAW5 IDDM results
Dr. Richard S. Spielman,
Max P. Baur,
Françoise Clerget-Darpoux,
Corresponding Author
Dr. Richard S. Spielman
Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia
Department of Human Genetics, 196 John Morgan Building, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6072Search for more papers by this authorMax P. Baur
Institut für Medizinische Statistik, Bonn - Venusberg, Federal Republic of Germany
Search for more papers by this authorFrançoise Clerget-Darpoux
INSERM U. 155, Chǎteau de Longchamp, Paris
Search for more papers by this authorDr. Richard S. Spielman,
Max P. Baur,
Françoise Clerget-Darpoux,
Corresponding Author
Dr. Richard S. Spielman
Department of Human Genetics, University of Pennsylvania School of Medicine, Philadelphia
Department of Human Genetics, 196 John Morgan Building, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6072Search for more papers by this authorMax P. Baur
Institut für Medizinische Statistik, Bonn - Venusberg, Federal Republic of Germany
Search for more papers by this authorFrançoise Clerget-Darpoux
INSERM U. 155, Chǎteau de Longchamp, Paris
Search for more papers by this authorAbstract
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 licus with one disese 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.
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