BMC Genetics (Dec 2017)

Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle

  • Taichi Arishima,
  • Shinji Sasaki,
  • Tomohiro Isobe,
  • Yoshihisa Ikebata,
  • Shinichi Shimbara,
  • Shogo Ikeda,
  • Keisuke Kawashima,
  • Yutaka Suzuki,
  • Manabu Watanabe,
  • Sumio Sugano,
  • Kazunori Mizoshita,
  • Yoshikazu Sugimoto

DOI
https://doi.org/10.1186/s12863-017-0573-8
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 12

Abstract

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Abstract Background Repeat breeding, which is defined as cattle failure to conceive after three or more inseminations in the absence of clinical abnormalities, is a substantial problem in cattle breeding. To identify maternal genetic variants of repeat breeding in Japanese Black cattle, we selected 29 repeat-breeding heifers that failed to conceive following embryo transfer (ET) and conducted a genome-wide association study (GWAS) using the traits. Results We found that a single-nucleotide polymorphism (SNP; g.92,377,635A > G) in the upstream region of the FOXP3 gene on the X chromosome was highly associated with repeat breeding and failure to conceive following ET (P = 1.51 × 10−14). FOXP3 is a master gene for differentiation of regulatory T (Treg) cells that function in pregnancy maintenance. Reporter assay results revealed that the activity of the FOXP3 promoter was lower in reporter constructs with the risk-allele than in those with the non-risk-allele by approximately 0.68 fold. These findings suggest that the variant in the upstream region of FOXP3 with the risk-allele decreased FOXP3 transcription, which in turn, could reduce the number of maternal Treg cells and lead to infertility. The frequency of the risk-allele in repeat-breeding heifers is more than that in cows, suggesting that the risk-allele could be associated with infertility in repeat-breeding heifers. Conclusions This GWAS identified a maternal variant in the upstream region of FOXP3 that was associated with infertility in repeat-breeding Japanese Black cattle that failed to conceive using ET. The variant affected the level of FOXP3 mRNA expression. Thus, the results suggest that the risk-allele could serve as a useful marker to reduce and eliminate animals with inferior fertility in Japanese Black cattle.

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