Dataset Information

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

ABSTRACT: 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.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.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.

SUBMITTER: Arishima T

PROVIDER: S-EPMC5719641 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Arishima Taichi T Sasaki Shinji S Isobe Tomohiro T Ikebata Yoshihisa Y Shimbara Shinichi S Ikeda Shogo S Kawashima Keisuke K Suzuki Yutaka Y Watanabe Manabu M Sugano Sumio S Mizoshita Kazunori K Sugimoto Yoshikazu Y

BMC genetics 20171206 1

<h4>Background</h4>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.<h4>Results</h4>We found that a single-nucleotide ...[more]

PMID: 29212449

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Project description:Female fertility, a fundamental trait required for animal reproduction, has gradually declined in the last 2 decades in Japanese Black cattle. To identify associated genetic variants in Japanese Black cattle, we evaluated female fertility as a metric to describe the average inverse of the number of artificial inseminations required for conception from the first through the fourth parity (ANAI4) and conducted a genome-wide association study (GWAS) using 430 animals with extreme ANAI4 values from 10,399 animals.We found that 2 variants, namely a single-nucleotide polymorphisms (SNP; g.48476925C?>?T) and a 3-bp indel (g.48476943_48476946insGGC), in the upstream region of the activin receptor IIA gene (ACVR2A) were associated with ANAI4. ACVR2A transcripts from Japanese Black cattle of the Q haplotype, defined by the SNP and the 3-bp indel, with increased ANAI4 were 1.29-1.32-fold more abundant than q-derived transcripts. In agreement, reporter assay results revealed that the activity of the ACVR2A promoter was higher in reporter constructs with the Q haplotype than in those with the q haplotype by approximately 1.2 fold. Expression of exogenous ACVR2A induced dose-dependent increases of reporter activity from the follicle-stimulating hormone, beta polypeptide (FSHB) promoter in response to activin A in a pituitary gonadotrophic cell line. The findings suggested that sequence variations in the upstream region of ACVR2A with the Q haplotype increased ACVR2A transcription, which in turn induced FSHB expression. This association was replicated using a sample population size of 1,433 animals; the frequency of the Q haplotype was 0.39, and Q-to-q haplotype substitution resulted in an increase of 0.02 in terms of ANAI4.This GWAS identified variants in the upstream region of ACVR2A, which were associated with female fertility in Japanese Black cattle. The variants affected the level of ACVR2A mRNA expression, which could lead to an allelic imbalance. This association was replicated with a sample population of 1,433 animals. Thus, the results suggest that the Q haplotype could serve as a useful marker to select Japanese Black cattle with superior female fertility.

Dataset Information

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

Publications

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

Similar Datasets

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