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Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle
BACKGROUND: Conception is a fundamental trait for successful cattle reproduction. However, conception rates in Japanese Black cattle have been gradually declining over the last two decades. Although conception failures are mainly caused by embryonic mortality, the role of maternal genetic factors in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122153/ https://www.ncbi.nlm.nih.gov/pubmed/27881083 http://dx.doi.org/10.1186/s12864-016-3312-z |
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author | Sasaki, Shinji Ibi, Takayuki Akiyama, Takayuki Fukushima, Moriyuki Sugimoto, Yoshikazu |
author_facet | Sasaki, Shinji Ibi, Takayuki Akiyama, Takayuki Fukushima, Moriyuki Sugimoto, Yoshikazu |
author_sort | Sasaki, Shinji |
collection | PubMed |
description | BACKGROUND: Conception is a fundamental trait for successful cattle reproduction. However, conception rates in Japanese Black cattle have been gradually declining over the last two decades. Although conception failures are mainly caused by embryonic mortality, the role of maternal genetic factors in the process remains unknown. Copy number variation (CNV), defined as large-scale genomic structural variants, contributes to several genetic disorders. To identify CNV associated with embryonic mortality in Japanese Black cattle, we evaluated embryonic mortality as a categorical trait with a threshold model and conducted a genome-wide CNV association study for embryonic mortality using 791 animals. RESULTS: We identified a deleted-type CNV ranging from 378,127 to 412,061 bp on bovine chromosome 8, which was associated with embryonic mortality at 30–60 days after artificial insemination (AI). The CNV harbors exon 2 to 6 of ANNEXIN A10 (ANXA10). Analysis of sequence traces from the CNV identified that 63 bp reads bridging the breakpoint were present on both sides of the CNV, indicating that the CNV was generated by non-allelic homologous recombination using the 63 bp homologous sequences. Western blot analysis showed that the CNV results in a null allele of ANXA10. This association was replicated using a sample population size of 2552 animals. To elucidate the function of ANXA10 in vivo, we generated Anxa10 null mice using the CRISPR/Cas9 system. Crossbreeding experiments showed that litter size from crosses of both Anxa10 (-/-) and Anxa10 (+/-) females had fewer pups than did Anxa10 (+/+) females, and embryos of Anxa10 (-/-) females died between implantation stages E4.5 and E12.5. These results indicate that loss of maternal Anxa10 causes embryonic mortality. CONCLUSIONS: This study identified a deleted-type CNV encompassing ANXA10 in cows that was associated with embryonic mortality at 30–60 days after AI. Using a mouse model, we confirmed that litter sizes were smaller in crosses of both Anxa10 (-/-) and Anxa10 (+/-) females relative to those of wild females. These results indicate that ANXA10 is a maternal factor that is critical for embryo development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3312-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5122153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-51221532016-11-30 Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle Sasaki, Shinji Ibi, Takayuki Akiyama, Takayuki Fukushima, Moriyuki Sugimoto, Yoshikazu BMC Genomics Research Article BACKGROUND: Conception is a fundamental trait for successful cattle reproduction. However, conception rates in Japanese Black cattle have been gradually declining over the last two decades. Although conception failures are mainly caused by embryonic mortality, the role of maternal genetic factors in the process remains unknown. Copy number variation (CNV), defined as large-scale genomic structural variants, contributes to several genetic disorders. To identify CNV associated with embryonic mortality in Japanese Black cattle, we evaluated embryonic mortality as a categorical trait with a threshold model and conducted a genome-wide CNV association study for embryonic mortality using 791 animals. RESULTS: We identified a deleted-type CNV ranging from 378,127 to 412,061 bp on bovine chromosome 8, which was associated with embryonic mortality at 30–60 days after artificial insemination (AI). The CNV harbors exon 2 to 6 of ANNEXIN A10 (ANXA10). Analysis of sequence traces from the CNV identified that 63 bp reads bridging the breakpoint were present on both sides of the CNV, indicating that the CNV was generated by non-allelic homologous recombination using the 63 bp homologous sequences. Western blot analysis showed that the CNV results in a null allele of ANXA10. This association was replicated using a sample population size of 2552 animals. To elucidate the function of ANXA10 in vivo, we generated Anxa10 null mice using the CRISPR/Cas9 system. Crossbreeding experiments showed that litter size from crosses of both Anxa10 (-/-) and Anxa10 (+/-) females had fewer pups than did Anxa10 (+/+) females, and embryos of Anxa10 (-/-) females died between implantation stages E4.5 and E12.5. These results indicate that loss of maternal Anxa10 causes embryonic mortality. CONCLUSIONS: This study identified a deleted-type CNV encompassing ANXA10 in cows that was associated with embryonic mortality at 30–60 days after AI. Using a mouse model, we confirmed that litter sizes were smaller in crosses of both Anxa10 (-/-) and Anxa10 (+/-) females relative to those of wild females. These results indicate that ANXA10 is a maternal factor that is critical for embryo development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3312-z) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-24 /pmc/articles/PMC5122153/ /pubmed/27881083 http://dx.doi.org/10.1186/s12864-016-3312-z Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Sasaki, Shinji Ibi, Takayuki Akiyama, Takayuki Fukushima, Moriyuki Sugimoto, Yoshikazu Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle |
title | Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle |
title_full | Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle |
title_fullStr | Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle |
title_full_unstemmed | Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle |
title_short | Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in Japanese Black cattle |
title_sort | loss of maternal annexin a10 via a 34-kb deleted-type copy number variation is associated with embryonic mortality in japanese black cattle |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122153/ https://www.ncbi.nlm.nih.gov/pubmed/27881083 http://dx.doi.org/10.1186/s12864-016-3312-z |
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