Type II diabetes remains a genetic nightmare. The major problem is identifying suitable pedigrees, sib-pairs, and populations for study. Segregation analysis data suggest that type II diabetes is likely to be polygenic, although one or more major genes could also be involved. This and the high prevalence of diabetes affect the strategies for searching for genetic mutations. Linkage analysis in classical type II diabetes pedigrees is unlikely to be successful. In addition, affected sib-pair analysis is limited because both parents are often affected, leading to bilineal inheritance. Sib-pairs with both parents alive are unusual, so identity by descent analysis is rarely feasible. Strategies to reduce bilineal inheritance by identifying sib-pairs with one known nondiabetic parent or with the second sibling having mild subclinical diabetes may be worthwhile. Identification of individuals or pedigrees with an unusual phenotype that suggests a single gene disorder, such as maturity-onset diabetes of the young, will continue to be important, for this allows linkage analysis with markers near candidate genes and exclusion mapping of chromosomal regions using highly polymorphic markers. Population association studies with candidate genes can detect mutations that have a minor role in the majority proportion of diabetic subjects, but large numbers are required and great care must be taken to exclude ethnic group differences between the diabetic and normoglycemic populations. The study of small inbred communities might be helpful because they may have fewer diabetogenic genes than outbred populations, and this would increase the power of sib-pair and population association studies. Direct screening for mutations in candidate genes (with single-strand conformation polymorphism or heteroduplex screening or with direct sequencing) in patients with the appropriate pathophysiological abnormality can be a successful strategy. The identification of well-defined diabetic pedigrees, sib-pairs, and suitable matched diabetic and nondiabetic populations will be key to the discovery of the genes for diabetes.
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Perspectives in Diabetes|
January 01 1995
Type II Diabetes: Clinical Aspects of Molecular Biological Studies
Robert C Turner;
Robert C Turner
Diabetes Research Laboratories
Radcliffe Infirmary, Oxford
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Andrew T Hattersley;
Andrew T Hattersley
Department of Medicine, Queen Elizabeth Hospital
Birmingham, U.K
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Joanne T Shaw;
Joanne T Shaw
Diabetes Research Laboratories
Radcliffe Infirmary, Oxford
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Jonathan C Levy
Jonathan C Levy
Diabetes Research Laboratories
Radcliffe Infirmary, Oxford
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Address correspondence and reprint requests to Dr. Robert C. Turner, Diabetes Research Laboratories, Radcliffe Infirmary, Woodstock Rd., Oxford 0X2 6HE, U.K
Diabetes 1995;44(1):1–10
Article history
Received:
June 27 1994
Revision Received:
September 22 1994
Accepted:
September 22 1994
PubMed:
7813802
Citation
Robert C Turner, Andrew T Hattersley, Joanne T Shaw, Jonathan C Levy; Type II Diabetes: Clinical Aspects of Molecular Biological Studies. Diabetes 1 January 1995; 44 (1): 1–10. https://doi.org/10.2337/diab.44.1.1
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