Genetic Factors in Type 2 Diabetes

All in the (Lipin) Family

  1. Karen Reue and
  2. Jimmy Donkor
  1. From the Departments of Human Genetics and Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California
  1. Address correspondence and reprint requests to Karen Reue, Department of Human Genetics, 6506A, David Geffen School of Medicine at UCLA, 695 Charles E. Young Drive South, Los Angeles, CA 90095. E-mail: reuek{at}ucla.edu

Type 2 diabetes was once referred to as a “geneticist’s nightmare” (1) due to difficulties stemming from the nature of the disease and the strategies available for genetic analysis. Two key genetic approaches previously utilized—linkage analysis and candidate gene association studies—each have limitations that have been difficult to overcome in the study of type 2 diabetes. Linkage studies have been hampered by difficulties in obtaining well-defined pedigrees because of the late onset of the disease, imprecise diagnostic criteria, and genetic heterogeneity. Association studies are limited in scope to the consideration of known genes that have an established biological link to diabetes.

One approach to overcome some of these difficulties is to couple genome-wide linkage analysis in genetically isolated populations with high-resolution typing of genetic variations across the linkage region. This was shown to be a viable approach for the identification of novel diabetes genes with the discovery of variants in TCF7L2, a gene encoding a ubiquitous transcription factor with no previous functional connection to diabetes (2). Importantly, subsequent studies have revealed a previously unknown …

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