Forskning ved Københavns Universitet - Københavns Universitet


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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Timothy M Frayling
  • Cecilia M Lindgren
  • Jean Claude Chevre
  • Stephan Menzel
  • Marie Wishart
  • Yamina Benmezroua
  • Alison Brown
  • Julie C Evans
  • Pamidghantam Subba Rao
  • Christian Dina
  • Cécile Lecoeur
  • Timo Kanninen
  • Peter Almgren
  • Michael P Bulman
  • Youxiang Wang
  • James Mills
  • Rosemarie Wright-Pascoe
  • Melanie M Mahtani
  • Francesco Prisco
  • Angels Costa
  • Ignacio Cognet
  • Sian Ellard
  • Tiinamaija Tuomi
  • Leif C Groop
  • Philippe Froguel
  • Andrew T Hattersley
  • Martine Vaxillaire
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.
Udgave nummer3
Sider (fra-til)872-81
Antal sider10
StatusUdgivet - 2003

ID: 38454575