Genetic analysis of IDDM: The GAW5 multiplex family dataset

Baur, Max P.; Fimmers, Rolf; Fritsche, Christiane; Hümmelink, M.; Neugebauer, M.; Acton, Ronald T.; Hodge, Thomas; Barbosa, José; Bertrams, J.; Fehsel, Karin; Kolb, Hubert; Rothe, Helga; Boehm, B. O.; Cambon‐Thomsen, Anne; Avoustin, P.; Coppin, Hélène; Darnaud, J; Massabie, P.; Ohayon, E; Préval, C. de; Tauber, J. P.; Thomsen, Mögens; Colle, Eleanor; MacDonald, Michael J.; Nevin, David; Jl, Gottschall; Nepom, Gerald T.; Robinson, David M.; Holbeck, Susan L.; Palmer, Jerry P.; Nerup, J.; Rotter, Jerome I.; Vadheim, Constance M.; Rittner, Christian; Schneider, P. M.; Sheehy, Michael J.; Cox, Nancy J.; Baker, Lester; Spielman, Richard S.

doi:10.1002/gepi.1370060105

Cited by 9 publications

(1 citation statement)

References 4 publications

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“…Then family studies were performed that allowed us to assign haplotypes as combinations of alleles that cosegregate and are transmitted to affected offspring. This approach focussed on pedigrees with multiple affected (multiplex) probands which were studied for genes known to confer susceptibility in prior patient/control comparisons (Baur et al, 1989;Cudworth and Woodrow, 1975;Gorsuch et al, 1982;Zerbib et al, 1989). The third step were large genome scanning studies in affected sib pairs (ASP) where microsatellite variants or single nucleotide polymorphisms (SNPs) were used as markers for potential association and thus novel regions could be identified (Fimmers et al, 1989).…”

Section: Proof Of a Genetic Association: Patients Controls And Familiesmentioning

confidence: 99%

Genetic Susceptibility and Immunological Synapse in Type 1 Diabetes and Thyroid Autoimmune Disease

Badenhoop¹,

Boehm²

2004

Exp Clin Endocrinol Diabetes

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Type 1 diabetes mellitus results from an immune mediated or idiopathic destruction of the pancreatic beta cells. Its aetiopathogenesis remains to be elucidated, despite great progress in the characterisation of beta-cell antigens, T-lymphocyte and antibody markers as well as whole genome screening. The incidence of type 1 diabetes is rising in most countries. Moreover, a considerable proportion of patients initially presenting with type 2 diabetes mellitus have an underlying type 1 diabetes with a latent course. A proportion of type 1 diabetes patients have concomittant thyroid autoimmune disease, either Hashimoto's thyroiditis or Graves' disease. Whereas Hashimoto's thyroiditis shares the same destructive immune process as type 1 diabetes, Graves' disease is unique in stimulating specifically the TSH-receptor through high-affinity immunoglobulins. However, both the thyroid autoimmune disorders and type 1 diabetes have susceptibility genes in common, implying shared pathways of immunopathogenesis. It has become clear that the genetic composition of a host at least partly determines the course of an immune response leading either to an organ-specific autoimmune disease or creating a state of balance where antibodies are hallmarks of (auto)immunity but normal function prevails. Genetic factors including MHC ( IDDM 1-genetic locus) and non-MHC genes (IDDM 2 - IDDM X) have been shown to determine susceptibility to autoimmunity in type 1 diabetes or lifelong tolerance. Currently the importance of the various diabetes associated genes is becoming clearer due to functional studies. Our review attempts to compile the relevant data that have accumulated in recent years and offers perspectives for prediction, prevention and possibly even therapy of immune-mediated endocrinopathies.

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Section: Proof Of a Genetic Association: Patients Controls And Familiesmentioning

confidence: 99%

Genetic Susceptibility and Immunological Synapse in Type 1 Diabetes and Thyroid Autoimmune Disease

Badenhoop¹,

Boehm²

2004

Exp Clin Endocrinol Diabetes

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Restriction fragment polymorphisms of the HLA‐DR, HLA‐DQ, and insulin gene regions in IDDM: The GAW5 data

Cox

Gogolin

Horváth

et al. 1989

Genetic Epidemiology

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The primary aim of the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5) was to collect and analyze new data on DNA polymorphisms closely linked to the HLA-D region and the insulin gene. The probes and restriction enzymes described here were used by all ten participating labs, and the data from Southern blotting were interpreted and reported according to conventions developed for the Workshop. These DNA data on members of 94 families with two or more IDDM sibs constitute the largest such sample available. The data were used in most of the analyses presented at the Workshop meeting, and are available on request.

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Genetic analysis of IDDM: Summary of GAW5 IDDM results

Spielman

Baur²,

Clerget‐Darpoux

1989

Genetic Epidemiology

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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.

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Genetic analysis of IDDM: The GAW5 multiplex family dataset

Cited by 9 publications

References 4 publications

Genetic Susceptibility and Immunological Synapse in Type 1 Diabetes and Thyroid Autoimmune Disease

Genetic Susceptibility and Immunological Synapse in Type 1 Diabetes and Thyroid Autoimmune Disease

Restriction fragment polymorphisms of the HLA‐DR, HLA‐DQ, and insulin gene regions in IDDM: The GAW5 data

Genetic analysis of IDDM: Summary of GAW5 IDDM results

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