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Genome-Wide Identification of a Regulatory Mutation in BMP15 Controlling Prolificacy in Sheep
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Edité par CCSD ; Frontiers Media -
International audience. 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 namedFecL(L). However, based on litter size (LS) records ofFecL(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 theBMP15gene was evidenced to be highly associated with the prolificacy variability (P= 1.93E-11). The variant allele was calledFecX(N)and shown to segregate also in the Blanche du Massif Central (BMC) sheep population. In both NV and BMC, theFecX(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. HomozygousFecX(N)carrier ewes were fertile with increased prolificacy in contrast to numerous mutations affectingBMP15. At the molecular level,FecX(N)was shown to decreaseBMP15promoter activity and supposed to impactBMP15expression in the oocyte. This regulatory action was proposed as the causal mechanism for theFecX(N)mutation to control ovulation rate and prolificacy in sheep.
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