Soutenance de Thèse - Mise en évidence et analyse fonctionnelle des mutations affectant la prolificité des ovins allaitants

In meat sheep, prolificacy (number of lambs per lambing) is one of the most important technical-economic levers to improve the breeders’ profitability. From a genetic point of view, this trait is lowly heritable. However, point mutations having a significant effect on increasing ovulation rate and prolificacy have been identified in four fecundity (Fec) genes, named FecB/BMPR1B, FecG/GDF9, FecX/BMP15 and FecL/B4GALNT2. The objective of this thesis was the identification of new or already known prolificacy mutations, mainly in French meat sheep breeds for which the segregation of such mutations was statistically hypothesized. By combining genetics, high-throughput genomics, and molecular and functional biology approaches, I identified five mutations with major effect on prolificacy in eight different sheep populations. All these mutations affect the fecundity genes already known, but two of them in the FecX/BMP15 gene are newly identified by this thesis work. In particular, the new FecXN mutation is, unlike the 9 other known prolific mutations in BMP15, located in the regulatory part of the gene inhibiting its expression. Once these mutations are identified, the information of frequency of the presence of each mutation in the populations and the effect on the reproductive physiology of the ewes must be considered for the management of breeding schemes. In this context, I particularly studied the FecLL mutation of the FecL/B4GALNT2 gene previously discovered in Lacaune sheep and that I also evidenced in the Noire du Velay breed. The FecLL mutation, known to increase the ewe prolificacy by +0.45 lamb per lambing, has no impact on the birth weight or growth rate of ewe lambs carrying this mutation. However, ewe lambs carrying FecLL have an advanced puberty of 2 months on average. This sexual precocity is however not explained by the observation of lower circulating concentrations of two ovarian hormones, AMH and inhibin A. Interestingly for the practice of animal insemination, ewes carrying FecLL are more fertile than non-carrier ewes partly due to their better sensitivity to the PMSG administration used to synchronize ovulations. All of this thesis work brings new elements to improve the genetic and physiological management of meat sheep populations in which a mutation with major effect on prolificacy segregates.