Fine-mapping of the type 1 diabetes locus (IDDM4) on chromosome 11q and evaluation of two candidate genes (FADD and GALN) by affected sibpair and linkage-disequilibrium analyses

Previous studies have identified a susceptibility region for insulin-dependent (type 1) diabetes mellitus on chromosome 11q13 (IDDM4). In this study, 15 polymorphic markers were analyzed for 382 affected sibpair (ASP) families with type 1 diabetes. Our analyses provided additional evidence for linka...

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Bibliographic Details
Published in:Human genetics 2000-01, Vol.106 (1), p.14-18
Main Authors: ECKENRODE, S, MARRON, M. P, NICHOLLS, R, YANG, M. C. K, YANG, J. J, GUIDAFONSECA, L. C, SHE, J.-X
Format: Article
Language:English
Subjects:
Bacterial Proteins - genetics
Biological and medical sciences
Chromosome Mapping
Chromosomes, Human, Pair 11
Coenzyme A Ligases - genetics
Diabetes Mellitus, Type 1 - genetics
Diabetes. Impaired glucose tolerance
DNA Mutational Analysis
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Escherichia coli Proteins
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Family Health
Galanin - genetics
Genetic Markers
Genetic Predisposition to Disease
Genotype
Humans
Linkage Disequilibrium
Medical sciences
Microsatellite Repeats
Polymorphism, Genetic
Polymorphism, Single-Stranded Conformational
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Summary:Previous studies have identified a susceptibility region for insulin-dependent (type 1) diabetes mellitus on chromosome 11q13 (IDDM4). In this study, 15 polymorphic markers were analyzed for 382 affected sibpair (ASP) families with type 1 diabetes. Our analyses provided additional evidence for linkage for IDDM4 (a peak LOD score of 3.4 at D11S913). The markers with strong linkage evidence are located within an interval of approximately 6 cM between D11S4205 and GALN. We also identified polymorphisms in two candidate genes, Fas-associated death domain protein (FADD) and galanin (GALN). Analyses of the data by transmission/disequilibrium test (TDT) and extended TDT (ETDT) did not provide any evidence for association/linkage with these candidate genes. However, ETDT did reveal significant association/linkage with the marker D11S987 (P=0.0004) within the IDDM4 interval defined by ASP analyses, suggesting that IDDM4 may be in the close proximity of D11S987.
ISSN:0340-6717
1432-1203
DOI:10.1007/s004399900186