Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression
Abstract Background An unfavorable genetic correlation between milk production and fertility makes simultaneous improvement of milk production and fertility difficult in cattle breeding. Rapid genetic improvement in milk production traits in dairy cattle has been accompanied by decline in cow fertil...
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-019-5638-9 |
| _version_ | 1819065440934035456 |
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| author | Zexi Cai Bernt Guldbrandtsen Mogens Sandø Lund Goutam Sahana |
| author_facet | Zexi Cai Bernt Guldbrandtsen Mogens Sandø Lund Goutam Sahana |
| author_sort | Zexi Cai |
| collection | DOAJ |
| description | Abstract Background An unfavorable genetic correlation between milk production and fertility makes simultaneous improvement of milk production and fertility difficult in cattle breeding. Rapid genetic improvement in milk production traits in dairy cattle has been accompanied by decline in cow fertility. The genetic basis of this correlation remains poorly understood. Expanded reference populations and large sets of sequenced animals make genome-wide association studies (GWAS) with imputed markers possible for large populations and thereby studying genetic architecture of complex traits. Results In this study, we associated 15,551,021 SNPs with female fertility index in 5038 Nordic Holstein cattle. We have identified seven quantitative trait loci (QTL) on six chromosomes in cattle. Along with nearest genes to GWAS hits, we used gene-based analysis and spread of linkage disequilibrium (LD) information to generate a list of potential candidate genes affecting fertility in cattle. Subsequently, we used prior knowledge on gene related to fertility from Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathway analysis, mammalian phenotype database, and public available RNA-seq data to refine the list of candidate genes for fertility. We used variant annotations to investigate candidate mutations within the prioritized candidate genes. Using multiple source of information, we proposed candidate genes with biological relevance underlying each of these seven QTL. On chromosome 1, we have identified ten candidate genes for two QTL. For the rest of chromosomes, we proposed one candidate gene for each QTL. In the candidate genes list, differentially expressed genes from different studies support FRAS1, ITGB5, ADCY5, and SEMA5B as candidate genes for cow fertility. Conclusion The GWAS result not only confirmed previously mapped QTL, but also made new findings. Our findings contributes towards dissecting the genetics for female fertility in cattle. Moreover, this study shows the usefulness of adding independent information to pick candidate genes during post-GWAS analysis. |
| first_indexed | 2024-12-21T15:46:30Z |
| format | Article |
| id | doaj.art-48a584130f9f482faa0a7387c1e89128 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-21T15:46:30Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-48a584130f9f482faa0a7387c1e891282022-12-21T18:58:21ZengBMCBMC Genomics1471-21642019-03-012011910.1186/s12864-019-5638-9Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expressionZexi Cai0Bernt Guldbrandtsen1Mogens Sandø Lund2Goutam Sahana3Center for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus UniversityCenter for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus UniversityCenter for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus UniversityCenter for Quantitative Genetics and Genomics, Department of Molecular Biology and Genetics, Aarhus UniversityAbstract Background An unfavorable genetic correlation between milk production and fertility makes simultaneous improvement of milk production and fertility difficult in cattle breeding. Rapid genetic improvement in milk production traits in dairy cattle has been accompanied by decline in cow fertility. The genetic basis of this correlation remains poorly understood. Expanded reference populations and large sets of sequenced animals make genome-wide association studies (GWAS) with imputed markers possible for large populations and thereby studying genetic architecture of complex traits. Results In this study, we associated 15,551,021 SNPs with female fertility index in 5038 Nordic Holstein cattle. We have identified seven quantitative trait loci (QTL) on six chromosomes in cattle. Along with nearest genes to GWAS hits, we used gene-based analysis and spread of linkage disequilibrium (LD) information to generate a list of potential candidate genes affecting fertility in cattle. Subsequently, we used prior knowledge on gene related to fertility from Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathway analysis, mammalian phenotype database, and public available RNA-seq data to refine the list of candidate genes for fertility. We used variant annotations to investigate candidate mutations within the prioritized candidate genes. Using multiple source of information, we proposed candidate genes with biological relevance underlying each of these seven QTL. On chromosome 1, we have identified ten candidate genes for two QTL. For the rest of chromosomes, we proposed one candidate gene for each QTL. In the candidate genes list, differentially expressed genes from different studies support FRAS1, ITGB5, ADCY5, and SEMA5B as candidate genes for cow fertility. Conclusion The GWAS result not only confirmed previously mapped QTL, but also made new findings. Our findings contributes towards dissecting the genetics for female fertility in cattle. Moreover, this study shows the usefulness of adding independent information to pick candidate genes during post-GWAS analysis.http://link.springer.com/article/10.1186/s12864-019-5638-9Dairy cattleFemale fertilityGene-base analysisGene annotationRNA-seq |
| spellingShingle | Zexi Cai Bernt Guldbrandtsen Mogens Sandø Lund Goutam Sahana Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression BMC Genomics Dairy cattle Female fertility Gene-base analysis Gene annotation RNA-seq |
| title | Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression |
| title_full | Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression |
| title_fullStr | Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression |
| title_full_unstemmed | Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression |
| title_short | Prioritizing candidate genes for fertility in dairy cows using gene-based analysis, functional annotation and differential gene expression |
| title_sort | prioritizing candidate genes for fertility in dairy cows using gene based analysis functional annotation and differential gene expression |
| topic | Dairy cattle Female fertility Gene-base analysis Gene annotation RNA-seq |
| url | http://link.springer.com/article/10.1186/s12864-019-5638-9 |
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