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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 (T reg ) 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 T reg  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.    Electronic supplementary material  The online version of this article (10.1186/s12863-017-0573-8) contains supplementary material, which is available to authorized users.

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