Dataset Information

Genome-Wide Identification of a Regulatory Mutation in BMP15 Controlling Prolificacy in Sheep.

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.

SUBMITTER: Chantepie L

PROVIDER: S-EPMC7317000 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-Wide Identification of a Regulatory Mutation in BMP15 Controlling Prolificacy in Sheep.

Chantepie Louise L Bodin Loys L Sarry Julien J Woloszyn Florent F Plisson-Petit Florence F Ruesche Julien J Drouilhet Laurence L Fabre Stéphane S

Frontiers in genetics 20200619

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 ...[more]

PMID: 32636872

Similar Datasets

Project description:Some sheep breeds are naturally prolific, and they are very informative for the studies of reproductive genetics and physiology. Major genes increasing litter size (LS) and ovulation rate (OR) were suspected in the French Grivette and the Polish Olkuska sheep populations, respectively. To identify genetic variants responsible for the highly prolific phenotype in these two breeds, genome-wide association studies (GWAS) followed by complementary genetic and functional analyses were performed. Highly prolific ewes (cases) and normal prolific ewes (controls) from each breed were genotyped using the Illumina OvineSNP50 Genotyping Beadchip. In both populations, an X chromosome region, close to the BMP15 gene, harbored clusters of markers with suggestive evidence of association at significance levels between 1E(-05) and 1E(-07). The BMP15 candidate gene was then sequenced, and two novel non-conservative mutations called FecX(Gr) and FecX(O) were identified in the Grivette and Olkuska breeds, respectively. The two mutations were associated with the highly prolific phenotype (p FecX (Gr) = 5.98E(-06) and p FecX(O) = 2.55E(-08)). Homozygous ewes for the mutated allele showed a significantly increased prolificacy (FecX(Gr)/FecX(Gr), LS = 2.50 ± 0.65 versus FecX(+)/FecX(Gr), LS = 1.93 ± 0.42, p<1E(-03) and FecX(O)/FecX(O), OR = 3.28 ± 0.85 versus FecX(+)/FecX(O), OR = 2.02 ± 0.47, p<1E(-03)). Both mutations are located in very well conserved motifs of the protein and altered the BMP15 signaling activity in vitro using a BMP-responsive luciferase test in COV434 granulosa cells. Thus, we have identified two novel mutations in the BMP15 gene associated with increased LS and OR. Notably, homozygous FecX(Gr)/FecX(Gr) Grivette and homozygous FecX(O)/FecX(O) Olkuska ewes are hyperprolific in striking contrast with the sterility exhibited by all other known homozygous BMP15 mutations. Our results bring new insights into the key role played by the BMP15 protein in ovarian function and could contribute to a better understanding of the pathogenesis of women's fertility disorders.

Dataset Information

Genome-Wide Identification of a Regulatory Mutation in BMP15 Controlling Prolificacy in Sheep.

Publications

Genome-Wide Identification of a Regulatory Mutation in BMP15 Controlling Prolificacy in Sheep.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets