I-53: Genetics of Infertility: How to CloneHuman Genes Solely Involved in InfertilityPhenotype

An increased proportion of couples require a medical help to conceive and 1-3.6% of pregnancies in occidental countries are obtained thanks to a Assistance Reproduction For more than half of them the cause of these dysfunctions remains unknown and in vitro fertilization is often proposed as a universal answer to a complex problem. Most of the proposed treatments are often empirical and little has been achieved to better understand the mechanisms underlying human fertility. This is not conforming to a medical practice of 2010. Little has been discovered in the field of male reproductive genetics since the discovery of chromosome Y microdeletions. Many groups looked in various cohorts of infertile patients for causal mutations in candidate genes. This strategy has mainly been unsuccessful probably mainly because of the tremendous genetic heterogeneity of this pathology. We recently demonstrated that whole genome homozygosity mapping applied to appropriate families or group of patients could provide high quality results (ref). This strategy, which highlights the presence of identical ancestral chromosomal regions is particularly suited to the study of large consanguineous families or inbred communities. In collaboration with centres in France, but especially in North Africa and the Middle East we have started recruiting patients with well defined phenotypes. These patients often come from small communities with little or no immigration and a high degree of intra-familial marriage. Husband and wife are thus often related andsusceptible to harbour the same rare dormant recessive mutation they have inherited from a common ancestor. Their children thus have a risk of ¼ to inherit the two copies of the mutation, thus to develop the syndrome. Since the mutation comes from a recent common ancestor the whole region surrounding the mutation willbe identical, therefore all the polymorphic markers of the area will be homozygous. In these situations, when the phenotype is homogeneous and the families inbred, the strategy of homozygosity mapping allows the identification of the regions likely to hold the mutation responsible for the investigated phenotypes. We have used this approach successfully in the past and believe that this strategy is likely to succeed in identifying many more genes involved in the reproductive process. I will present our latest results in this field. Indeed, we have identified new genes solely involved in male infertility. I will also make a call for collaborations in this specific area of research.