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Feed efficiency is a major production trait in animal genetic breeding schemes. To further investigate the genetic control of feed efficiency in rabbits, we performed a genome-wide association study (GWAS) for growth and feed efficiency on 679 rabbits genotyped with the Affimetrix Axiom Rabbit 200K Genotyping Array. After quality control, 127 847 single-nucleotide polymorphisms (SNP) were retained for association analyses. The GWAS were performed using GEMMA software, applying a mixed univariate animal model with a linear regression on each SNP allele. The traits analysed were weight at weaning and at 63 days of age, average daily gain, total individual feed intake, feed conversion ratio and residual feed intake. No significant SNP was found for growth traits or feed intake. Fifteen genome-wide significant SNPs were detected for feed conversion ratio on OCU7, spanning from 124.8 Mbp to 126.3 Mbp, plus two isolated SNP on OCU2 (77.3 Mbp) and OCU8 (16.5 Mbp). For residual feed intake, a region on OCU18 (46.1-53.0 Mbp) was detected, which contained a putative functional candidate gene, GOT1.

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 FecLL. However, based on litter size (LS) records of FecLL 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 FecXN and shown to segregate also in the Blanche du Massif Central (BMC) sheep population. In both NV and BMC, the FecXN 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 FecXN carrier ewes were fertile with increased prolificacy in contrast to numerous mutations affecting BMP15. At the molecular level, FecXN 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 FecXN mutation to control ovulation rate and prolificacy in sheep.