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Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins

Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception...

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Autores principales: Sugimoto, Mayumi, Gotoh, Yusaku, Kawahara, Takayoshi, Sugimoto, Yoshikazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493121/
https://www.ncbi.nlm.nih.gov/pubmed/26147436
http://dx.doi.org/10.1371/journal.pone.0131283
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author Sugimoto, Mayumi
Gotoh, Yusaku
Kawahara, Takayoshi
Sugimoto, Yoshikazu
author_facet Sugimoto, Mayumi
Gotoh, Yusaku
Kawahara, Takayoshi
Sugimoto, Yoshikazu
author_sort Sugimoto, Mayumi
collection PubMed
description Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3’ untranslated region (UTR) of unc-5 homolog C (UNC5C). Cows with higher conception rates carried the A polymorphism in the UNC5C 3’UTR. Luciferase assays and quantitative analysis of allele ratios revealed that UNC5C transcripts with the A polymorphism were expressed at higher levels than those carrying the G polymorphism. UNC5C transmits either pro- or anti-apoptotic signals depending on the availability of its ligand, Netrin-1. UNC5C expression is negatively regulated by reproductive homeobox X-linked 5 (Rhox5), and the Rhox5 locus is methylated by G9a methyltransferase. G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased. Repression of UNC5C, G9a, or Netrin-1 or forced expression of Rhox5 in the anterior nucleus stage inhibited development to the blastocyst stage, suggesting that cows carrying the G polymorphism in UNC5C might have lower conception rates because of the poor development of preimplantation embryos. This study provides novel insights into the role of UNC5C during embryonic development.
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spelling pubmed-44931212015-07-15 Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins Sugimoto, Mayumi Gotoh, Yusaku Kawahara, Takayoshi Sugimoto, Yoshikazu PLoS One Research Article Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3’ untranslated region (UTR) of unc-5 homolog C (UNC5C). Cows with higher conception rates carried the A polymorphism in the UNC5C 3’UTR. Luciferase assays and quantitative analysis of allele ratios revealed that UNC5C transcripts with the A polymorphism were expressed at higher levels than those carrying the G polymorphism. UNC5C transmits either pro- or anti-apoptotic signals depending on the availability of its ligand, Netrin-1. UNC5C expression is negatively regulated by reproductive homeobox X-linked 5 (Rhox5), and the Rhox5 locus is methylated by G9a methyltransferase. G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased. Repression of UNC5C, G9a, or Netrin-1 or forced expression of Rhox5 in the anterior nucleus stage inhibited development to the blastocyst stage, suggesting that cows carrying the G polymorphism in UNC5C might have lower conception rates because of the poor development of preimplantation embryos. This study provides novel insights into the role of UNC5C during embryonic development. Public Library of Science 2015-07-06 /pmc/articles/PMC4493121/ /pubmed/26147436 http://dx.doi.org/10.1371/journal.pone.0131283 Text en © 2015 Sugimoto et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sugimoto, Mayumi
Gotoh, Yusaku
Kawahara, Takayoshi
Sugimoto, Yoshikazu
Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins
title Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins
title_full Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins
title_fullStr Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins
title_full_unstemmed Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins
title_short Molecular Effects of Polymorphism in the 3’UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins
title_sort molecular effects of polymorphism in the 3’utr of unc-5 homolog c associated with conception rate in holsteins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493121/
https://www.ncbi.nlm.nih.gov/pubmed/26147436
http://dx.doi.org/10.1371/journal.pone.0131283
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