Abstract

The genetics of non-insulin dependent diabetes (NIDDM; Type 2 diabetes) will be studied in the Pima Indian Tribe. This collaborative study will include the efforts of molecular geneticists, epidemiologists and clinicians focused on finding the inherited factors which lead to NIDDM. A large number of multiplex families and sib pairs have been identified and collected and some DNA typing and analysis has been carried out already. Initially efforts will be focused on 4 regions of human chromosomes which show some evidence for linkage to NIDDM using sib-pair analysis. In addition, numerous candidate genes will also be surveyed and a systematic survey of the genome will be continued using highly polymorphic microsatellite repeat polymorphisms and restriction fragment length polymorphisms. Data will be analyzed using a number of different linkage analysis approaches including sib-pair analysis, conventional linkage analysis, and also quantitative measures of traits such as obesity, glucose tolerance and insulin resistance. Detection of linkage will be followed by detailed molecular genetic analysis to determine the basis of NIDDM susceptibility. Linkages will also be tested in other populations and ethnic groups.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK047480-05
Application #
2518354
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Mckeon, Catherine T
Project Start
1993-09-30
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1999-08-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Biochemistry
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106

  Publications

Freedman, Barry I; Rich, Stephen S; Yu, Hongrun et al. (2002) Linkage heterogeneity of end-stage renal disease on human chromosome 10. Kidney Int 62:770-4
Yu, H; Anderson, P J; Freedman, B I et al. (2000) Genomic structure of the human plasma prekallikrein gene, identification of allelic variants, and analysis in end-stage renal disease. Genomics 69:225-34
Yu, H; Sale, M; Rich, S S et al. (1999) Evaluation of markers on human chromosome 10, including the homologue of the rodent Rf-1 gene, for linkage to ESRD in black patients. Am J Kidney Dis 33:294-300
Yu, H; Bowden, D W; Spray, B J et al. (1998) Identification of human plasma kallikrein gene polymorphisms and evaluation of their role in end-stage renal disease. Hypertension 31:906-11
Bowden, D W; Sale, M; Howard, T D et al. (1997) Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy. Diabetes 46:882-6
Freedman, B I; Yu, H; Spray, B J et al. (1997) Genetic linkage analysis of growth factor loci and end-stage renal disease in African Americans. Kidney Int 51:819-25
Howard, T D; Akots, G; Bowden, D W (1996) Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): reassignment to human chromosome 12q. Genomics 34:122-7
Yu, H; Bowden, D W; Spray, B J et al. (1996) Linkage analysis between loci in the renin-angiotensin axis and end-stage renal disease in African Americans. J Am Soc Nephrol 7:2559-64
Rothschild, C B; Freedman, B I; Hodge, R et al. (1995) Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus. Genomics 29:187-94