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

Hum Genet. 2000 Jan;106(1):14-8. doi: 10.1007/s004399900186.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11*
  • Coenzyme A Ligases / genetics*
  • DNA Mutational Analysis
  • Diabetes Mellitus, Type 1 / genetics*
  • Escherichia coli Proteins*
  • Family Health
  • Galanin / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Linkage Disequilibrium*
  • Microsatellite Repeats
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational

Substances

  • Bacterial Proteins
  • Escherichia coli Proteins
  • Genetic Markers
  • Galanin
  • Coenzyme A Ligases
  • acyl-coenzyme A synthetase, E coli