A genome-wide scan in families with maturity-onset diabetes of the young: evidence for further genetic heterogeneity

Diabetes. 2003 Mar;52(3):872-81. doi: 10.2337/diabetes.52.3.872.

Abstract

Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non-insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15-20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of beta-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169-175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosomes, Human, Pair 10
  • Chromosomes, Human, Pair 3
  • Chromosomes, Human, Pair 5
  • Chromosomes, Human, Pair 6
  • DNA-Binding Proteins*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Heterogeneity*
  • Genetic Linkage
  • Genotype
  • Glucokinase / genetics
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Lod Score
  • Male
  • Microsatellite Repeats
  • Mutation
  • Nuclear Proteins*
  • Pedigree
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Nuclear Proteins
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • Glucokinase