AUTHOR=Chantepie Louise , Bodin Loys , Sarry Julien , Woloszyn Florent , Plisson-Petit Florence , Ruesche Julien , Drouilhet Laurence , Fabre Stéphane TITLE=Genome-Wide Identification of a Regulatory Mutation in BMP15 Controlling Prolificacy in Sheep JOURNAL=Frontiers in Genetics VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00585 DOI=10.3389/fgene.2020.00585 ISSN=1664-8021 ABSTRACT=

The search for the genetic determinism of prolificacy variability in sheep has evidenced several major mutations in genes playing a crucial role in the control of ovulation rate. In the Noire du Velay (NV) sheep population, a recent genetic study has evidenced the segregation of such a mutation named FecL^L. However, based on litter size (LS) records of FecL^L non-carrier ewes, the segregation of a second prolificacy major mutation was suspected in this population. In order to identify this mutation, we have combined a case/control genome-wide association study with ovine 50k SNP chip genotyping, whole genome sequencing, and functional analyses. A new single nucleotide polymorphism (OARX:50977717T > A, NC_019484) located on the X chromosome upstream of the BMP15 gene was evidenced to be highly associated with the prolificacy variability (P = 1.93E-11). The variant allele was called FecX^N and shown to segregate also in the Blanche du Massif Central (BMC) sheep population. In both NV and BMC, the FecX^N allele frequency was estimated close to 0.10, and its effect on LS was estimated at +0.20 lamb per lambing at the heterozygous state. Homozygous FecX^N carrier ewes were fertile with increased prolificacy in contrast to numerous mutations affecting BMP15. At the molecular level, FecX^N was shown to decrease BMP15 promoter activity and supposed to impact BMP15 expression in the oocyte. This regulatory action was proposed as the causal mechanism for the FecX^N mutation to control ovulation rate and prolificacy in sheep.