Genetic Analysis of Endometriosis

Endometriosis is a common, benign, oestrogen-dependent, gynaecological disorder that occurs in women in their reproductive years. Although it has been studied for many years, the aetiology and pathophysiology of endometriosis are still unclear. Accumulated evidence indicates that endometriosis has a heritable component. Recently, the International Endogene Study (IES) identified two significant linkage regions on chromosomes 7 and 10. The signal on chromosome 7 may be caused by a rare variant, with near-Mendelian inheritance, present in a subset of families. This thesis comprises follow-up studies aimed at: 1) narrowing down the linkage region on chromosome 7 through fine mapping and haplotype analyses; 2) screening candidate genes for mutations potentially responsible for the susceptibility to endometriosis through sequencing, and 3) conducting linkage analyses in two orthologous regions in a large, complex pedigree of rhesus monkeys with spontaneous disease. Firstly, linkage and haplotype analyses were conducted on 32 extended families, which contributed most to the linkage signal, from the Oxford dataset. Haplotype analyses narrowed down the linkage region to an area surrounding a single marker (D7S2251), ... (continues)