Polycystic ovary syndrome (PCOS) is a common form of anovulatory infertility in women affecting 4-10% of reproductive age women. It is associated with obesity, insulin resistance, and Type 2 diabetes mellitus. Both environmental and genetic factors are believed to play a role in the pathogenesis of the syndrome. Multiple studies have shown evidence of familial clustering of PCOS indicating that there is a genetic component to the etiology of PCOS. However, the mode of inheritance of PCOS remains unclear, and to date no susceptibility genes for PCOS have been identified. From a series of linkage and association studies we have accumulated strong evidence for a susceptibility gene that maps near D19S884, an anonymous dinucleotide repeat marked, on Chr19p13.3. Forty putative genes map to within 250 kb of D19S884 including 13 confirmed genes, 16 mRNAs or spliced ESTs, and 11 predicted genes. The goal of this project is to identify the gene(s) and its variant(s) that maps to this region and characterize the role that the protein product of the gene plays in the etiology of PCOS. Our approach to identifying the PCOS susceptibility gene mapping in this region consists of three research aims; 1) to identify sequence variants in genes mapping near D19S884 in PCOS patients, 2) to differentiate between common polymorphism found in the general population and variants relevant to the etiology of PCOS, and 3) evaluate the functional consequences of variants identified in Aims 1 and 2. The identification of a PCOS susceptibility gene will shed light onto the etiology of a chronic disorder that affects literally millions of women in the United States and is expected to result in improved treatment and diagnosis for both PCOS and related phenotypes including type 2 diabetes mellitus, obesity, and cardiovascular disease.
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