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Genome-wide identification of a regulatory mutation in BMP15 controlling prolificacy in sheep
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Publié dans BioRXiv. 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 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 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 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 to impact BMP15 expression in oocyte. This regulatory action was proposed as the causal mechanism for the FecX N mutation to control ovulation rate and prolificacy in sheep.
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