title: A genome-wide scan in families with maturity-onset diabetes of the young: evidence for further genetic heterogeneity.
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.
authors.affiliation: Department of Diabetes and Vascular Medicine, Postgraduate School of Medicine and Health Science, University of Exeter, Exeter, U.K.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Chevre
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.forename: Marie
authors.initials: M
authors.lastname: Wishart
authors.forename: Yamina
authors.initials: Y
authors.lastname: Benmezroua
authors.forename: Alison
authors.initials: A
authors.lastname: Brown
authors.forename: Julie C
authors.initials: JC
authors.lastname: Evans
authors.forename: Pamidghantam Subba
authors.initials: PS
authors.lastname: Rao
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Cécile
authors.initials: C
authors.lastname: Lecoeur
authors.forename: Timo
authors.initials: T
authors.lastname: Kanninen
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Michael P
authors.initials: MP
authors.lastname: Bulman
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Wang
authors.forename: James
authors.initials: J
authors.lastname: Mills
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Wright-Pascoe
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Mahtani
authors.forename: Francesco
authors.initials: F
authors.lastname: Prisco
authors.forename: Angels
authors.initials: A
authors.lastname: Costa
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cognet
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
authors.forename: Leif C
authors.initials: LC
authors.lastname: Groop
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Martine
authors.initials: M
authors.lastname: Vaxillaire
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002879:Chromosomes, Human, Pair 10; D002893:Chromosomes, Human, Pair 3; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D004268:DNA-Binding Proteins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005838:Genotype; D005941:Glucokinase / Q000235:genetics; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009687:Nuclear Proteins; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D005941:Glucokinase