Genetics of Endometriosis: A Review of the Positional Cloning Approaches

There is increasing evidence that endometriosis is inherited as a complex genetic trait in which multiple genes conferring disease susceptibility interact with each other and the environment to produce the phenotype. Research groups worldwide are trying to identify such susceptibility genes through a “positional cloning” approach. This involves mapping their approximate chromosomal localization using linkage analysis by studying the segregation of DNA markers with disease in families without any knowledge of disease mechanisms. The next stage involves choosing a candidate gene in that region, based upon some theoretical or actual knowledge of disease mechanisms, and showing that polymorphisms in that gene occur more frequently in affected individuals than in controls. The approach should produce a clearer understanding of the molecular and cellular mechanisms involved in disease etiology and pathogenesis. It is unlikely that endometriosis is a single disease entity, and it should be possible to categorize the disease into subtypes on the basis of genetic information. The strategy should lead to the discovery of new drug targets, which will be a major advance given that treatment to date has focused upon crude manipulation of ovarian function.

Endometriosis - genetics - positional cloning

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