Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle
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...
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BMC
2017-12-01
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| Series: | BMC Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12863-017-0573-8 |
| _version_ | 1811289916226666496 |
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| author | Taichi Arishima Shinji Sasaki Tomohiro Isobe Yoshihisa Ikebata Shinichi Shimbara Shogo Ikeda Keisuke Kawashima Yutaka Suzuki Manabu Watanabe Sumio Sugano Kazunori Mizoshita Yoshikazu Sugimoto |
| author_facet | Taichi Arishima Shinji Sasaki Tomohiro Isobe Yoshihisa Ikebata Shinichi Shimbara Shogo Ikeda Keisuke Kawashima Yutaka Suzuki Manabu Watanabe Sumio Sugano Kazunori Mizoshita Yoshikazu Sugimoto |
| author_sort | Taichi Arishima |
| collection | DOAJ |
| description | 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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| format | Article |
| id | doaj.art-b1f3b614b7074265ba1e4ad13347d3cc |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-04-13T04:02:34Z |
| publishDate | 2017-12-01 |
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| series | BMC Genetics |
| spelling | doaj.art-b1f3b614b7074265ba1e4ad13347d3cc2022-12-22T03:03:25ZengBMCBMC Genetics1471-21562017-12-0118111210.1186/s12863-017-0573-8Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattleTaichi Arishima0Shinji Sasaki1Tomohiro Isobe2Yoshihisa Ikebata3Shinichi Shimbara4Shogo Ikeda5Keisuke Kawashima6Yutaka Suzuki7Manabu Watanabe8Sumio Sugano9Kazunori Mizoshita10Yoshikazu Sugimoto11Kagoshima prefectural Cattle Breeding Development InstituteNational Livestock Breeding CenterKagoshima prefectural Cattle Breeding Development InstituteKagoshima prefectural Cattle Breeding Development InstituteKagoshima prefectural Cattle Breeding Development InstituteKagoshima prefectural Cattle Breeding Development InstituteKagoshima prefectural Cattle Breeding Development InstituteDepartment of Medical Genome Sciences, and Department of Computational Biology, Graduate School of Frontier Sciences, The University of TokyoDepartment of Medical Genome Sciences, and Department of Computational Biology, Graduate School of Frontier Sciences, The University of TokyoDepartment of Medical Genome Sciences, and Department of Computational Biology, Graduate School of Frontier Sciences, The University of TokyoKagoshima prefectural Cattle Breeding Development InstituteShirakawa Institute of Animal Genetics, Japan Livestock Technology AssociationAbstract 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.http://link.springer.com/article/10.1186/s12863-017-0573-8Repeat breedingInfertilityEmbryo transfer (ET)FOXP3Genome-wide association study (GWAS)Beef cattle |
| spellingShingle | Taichi Arishima Shinji Sasaki Tomohiro Isobe Yoshihisa Ikebata Shinichi Shimbara Shogo Ikeda Keisuke Kawashima Yutaka Suzuki Manabu Watanabe Sumio Sugano Kazunori Mizoshita Yoshikazu Sugimoto Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle BMC Genetics Repeat breeding Infertility Embryo transfer (ET) FOXP3 Genome-wide association study (GWAS) Beef cattle |
| title | Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle |
| title_full | Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle |
| title_fullStr | Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle |
| title_full_unstemmed | Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle |
| title_short | Maternal variant in the upstream of FOXP3 gene on the X chromosome is associated with recurrent infertility in Japanese Black cattle |
| title_sort | maternal variant in the upstream of foxp3 gene on the x chromosome is associated with recurrent infertility in japanese black cattle |
| topic | Repeat breeding Infertility Embryo transfer (ET) FOXP3 Genome-wide association study (GWAS) Beef cattle |
| url | http://link.springer.com/article/10.1186/s12863-017-0573-8 |
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