Advanced

A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity.

Frayling, Timothy M. ; Lindgren, Cecilia LU ; Chevre, Jean Claude ; Menzel, Stephan ; Wishart, Marie ; Benmezroua, Yamina ; Brown, Alison ; Evans, Julie C. ; Rao, Pamidghantam Subba and Dina, Christian , et al. (2003) In Diabetes 52(3). p.872-881
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 β-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... (More)
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 β-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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
52
issue
3
pages
872 - 881
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000181364000038
  • pmid:12606533
  • scopus:0344837809
ISSN
1939-327X
DOI
10.2337/diabetes.52.3.872
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Endocrinology (013241500), Pediatrics/Urology/Gynecology/Endocrinology (013240400), Diabetes and Endocrinology (013241530)
id
8245a967-003d-4ed6-9576-8a4e996543b2 (old id 112144)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12606533&dopt=Abstract
date added to LUP
2016-04-01 16:10:17
date last changed
2020-03-11 05:30:45
@article{8245a967-003d-4ed6-9576-8a4e996543b2,
  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 β-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.},
  author       = {Frayling, Timothy M. and Lindgren, Cecilia and Chevre, Jean Claude and Menzel, Stephan and Wishart, Marie and Benmezroua, Yamina and Brown, Alison and Evans, Julie C. and Rao, Pamidghantam Subba and Dina, Christian and Lecoeur, Cécile and Kanninen, Timo and Almgren, Peter and Bulman, Michael P. and Wang, Youxiang and Mills, James and Wright-Pascoe, Rosemarie and Mahtani, Melanie M. and Prisco, Francesco and Costa, Angels and Cognet, Ignacio and Hansen, Torben and Pedersen, Oluf and Ellard, Sian and Tuomi, Tiinamaija and Groop, Leif and Froguel, Philippe and Hattersley, Andrew T. and Vaxillaire, Martine},
  issn         = {1939-327X},
  language     = {eng},
  number       = {3},
  pages        = {872--881},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity.},
  url          = {http://dx.doi.org/10.2337/diabetes.52.3.872},
  doi          = {10.2337/diabetes.52.3.872},
  volume       = {52},
  year         = {2003},
}