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 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.
Eckenrode
S
S
Department of Pathology, Immunology and Laboratory Medicine, and Center for Mammalian Genetics, College of Medicine, University of Florida, Gainesville 32610, USA.
Marron
M P
MP
Nicholls
R
R
Yang
M C
MC
Yang
J J
JJ
Guida Fonseca
L C
LC
She
J X
JX
D001426:Bacterial Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003066:Coenzyme A Ligases / Q000235:genetics*; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D029968:Escherichia coli Proteins; D005192:Family Health; D019004:Galanin / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D005819:Genetic Markers; D019004:Galanin; D003066:Coenzyme A Ligases; C085934:acyl-coenzyme A synthetase, E coli