Abstract

The goal of this study is to map, clone, sequence, and determine the function of genes, which cause type 2 diabetes. Multiple studies now suggest that one or more genes in the region of chromosome 20q12-13.1 contribute to type 2 diabetes susceptibility in Caucasians. In order to determine the number of genes and contribution which they make to type 2 diabetes susceptibility, the mutant forms of these genes will be identified. The putative type 2 susceptibility genes within 20q12-q13.1 will be precisely defined through disequilibrium analysis using high density SNP maps in a variety of study groups including case-control and sibling pairs discordant for type 2 diabetes. An accurate correlation, expressed sequence physical map of chromosome 20q12-q13.1 will provide the framework for focused analysis of specific regions for linkage disequilibrium. Identification of candidate type 2 diabetes loci in the genetically defined region will be carried out by a detailed sequence survey of genes and non-gene sequences with the initial focus on sequences which are under disequilibrium peaks. SSCP and DNA sequence analysis of aberrantly migrating peaks will be used for this purpose. This effort will be complemented by analysis of increasing volume of sequence from the HGP. Polymorphic sequences which are candidate diabetogenic loci will be surveyed for differences in distribution between normal and type 2 diabetes-affected individuals to identify the diabetogenic gene. Based on SNP disequilibrium studies, coding and non-coding polymorphisms strongly associated with diabetes will be functionally evaluated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK056289-03
Application #
6624909
Study Section
Metabolism Study Section (MET)
Program Officer
Mckeon, Catherine T
Project Start
2001-02-15
Project End
2004-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
3
Fiscal Year
2003
Total Cost
$383,459
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Biochemistry
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157

  Publications

Hellwege, Jacklyn N; Hicks, Pamela J; Palmer, Nicholette D et al. (2011) Examination of Rare Variants in HNF4 ? in European Americans with Type 2 Diabetes. J Diabetes Metab 2:
Lewis, Joshua P; Palmer, Nicholette D; Ellington, Jennifer B et al. (2010) Analysis of candidate genes on chromosome 20q12-13.1 reveals evidence for BMI mediated association of PREX1 with type 2 diabetes in European Americans. Genomics 96:211-9
Palmer, Nicholette D; Lehtinen, Allison B; Langefeld, Carl D et al. (2008) Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans. J Clin Endocrinol Metab 93:304-9
Bento, J L; Palmer, N D; Zhong, M et al. (2008) Heterogeneity in gene loci associated with type 2 diabetes on human chromosome 20q13.1. Genomics 92:226-34
Burdon, Kathryn P; Bento, Jennifer L; Langefeld, Carl D et al. (2006) Association of protein tyrosine phosphatase-N1 polymorphisms with coronary calcified plaque in the Diabetes Heart Study. Diabetes 55:651-8
Bento, Jennifer L; Bowden, Donald W; Mychaleckyj, Josyf C et al. (2005) Genetic analysis of the GLUT10 glucose transporter (SLC2A10) polymorphisms in Caucasian American type 2 diabetes. BMC Med Genet 6:42
Segade, Fernando; Allred, Dax C; Bowden, Donald W (2005) Functional characterization of the promoter of the human glucose transporter 10 gene. Biochim Biophys Acta 1730:147-58
Bagwell, Allison M; Bento, Jennifer L; Mychaleckyj, Josyf C et al. (2005) Genetic analysis of HNF4A polymorphisms in Caucasian-American type 2 diabetes. Diabetes 54:1185-90
Palmer, Nicholette D; Bento, Jennifer L; Mychaleckyj, Josyf C et al. (2004) Association of protein tyrosine phosphatase 1B gene polymorphisms with measures of glucose homeostasis in Hispanic Americans: the insulin resistance atherosclerosis study (IRAS) family study. Diabetes 53:3013-9
Bagwell, Allison M; Bailly, Alain; Mychaleckyj, Josyf C et al. (2004) Comparative genomic analysis of the HNF-4alpha transcription factor gene. Mol Genet Metab 81:112-21

Showing the most recent 10 out of 14 publications