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Pima Indians as a model to study the genetics of NIDDM

โœ Scribed by Clifton Bogardus; Stephen Lillioja


Publisher
John Wiley and Sons
Year
1992
Tongue
English
Weight
681 KB
Volume
48
Category
Article
ISSN
0730-2312

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โœฆ Synopsis


More than half the Pima Indians over 35 years of age have non-insulin dependent diabetes mellitus (NIDDM). They have been the focus of prospective epidemiologic and metabolic studies for over two decades and the data collected during these studies are now proving invaluable in efforts to find genetic markers for NIDDM in humans. The Pima Indian model of this disease affords two major advantages. The population is genetically homogeneous compared to Caucasian populations, and therefore the causes of NlDDM are less heterogeneous, simplifying genetic linkage studies. Equally important, based on results from metabolic studies, two pre-diabetic phenotypes have been identified in the Pimas: insulin resistance and a low metabolic rate. Use of these phenotypes in genetic linkage analyses should greatly improve chances of finding genetic markers for NlDDM since these phenotypes may be more closely related to the putative abnormal gene products, and actual disease genes, than is the hyperglycemia of the fully developed phenotype of NIDDM.


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Segregation analysis suggests that the high prevalence of non-insulin-dependent diabetes mellitus in Pima Indians may be partially due to a single locus with a major effect on age of onset. A simulation study was conducted to evaluate the power of various age-adjustment strategies in linkage analysi