A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle.
Clinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has be...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-07-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009331 |
| _version_ | 1831834569691627520 |
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| author | Young-Lim Lee Haruko Takeda Gabriel Costa Monteiro Moreira Latifa Karim Erik Mullaart Wouter Coppieters GplusE consortium Ruth Appeltant Roel F Veerkamp Martien A M Groenen Michel Georges Mirte Bosse Tom Druet Aniek C Bouwman Carole Charlier |
| author_facet | Young-Lim Lee Haruko Takeda Gabriel Costa Monteiro Moreira Latifa Karim Erik Mullaart Wouter Coppieters GplusE consortium Ruth Appeltant Roel F Veerkamp Martien A M Groenen Michel Georges Mirte Bosse Tom Druet Aniek C Bouwman Carole Charlier |
| author_sort | Young-Lim Lee |
| collection | DOAJ |
| description | Clinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has been lacking. Herein, we mapped, fine-mapped, and discovered the putative causal variant underlying this CM resistance QTL in the Dutch dairy cattle population. We identified a ~12 kb multi-allelic copy number variant (CNV), that is in perfect linkage disequilibrium with a lead SNP, as a promising candidate variant. By implementing a fine-mapping and through expression QTL mapping, we showed that the group-specific component gene (GC), a gene encoding a vitamin D binding protein, is an excellent candidate causal gene for the QTL. The multiplicated alleles are associated with increased GC expression and low CM resistance. Ample evidence from functional genomics data supports the presence of an enhancer within this CNV, which would exert cis-regulatory effect on GC. We observed that strong positive selection swept the region near the CNV, and haplotypes associated with the multiplicated allele were strongly selected for. Moreover, the multiplicated allele showed pleiotropic effects for increased milk yield and reduced fertility, hinting that a shared underlying biology for these effects may revolve around the vitamin D pathway. These findings together suggest a putative causal variant of a CM resistance QTL, where a cis-regulatory element located within a CNV can alter gene expression and affect multiple economically important traits. |
| first_indexed | 2024-12-23T04:17:18Z |
| format | Article |
| id | doaj.art-d921bbd9c2d64991a5170e8cd04d0c66 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T04:17:18Z |
| publishDate | 2021-07-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj.art-d921bbd9c2d64991a5170e8cd04d0c662022-12-21T18:00:22ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-07-01177e100933110.1371/journal.pgen.1009331A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle.Young-Lim LeeHaruko TakedaGabriel Costa Monteiro MoreiraLatifa KarimErik MullaartWouter CoppietersGplusE consortiumRuth AppeltantRoel F VeerkampMartien A M GroenenMichel GeorgesMirte BosseTom DruetAniek C BouwmanCarole CharlierClinical mastitis (CM) is an inflammatory disease occurring in the mammary glands of lactating cows. CM is under genetic control, and a prominent CM resistance QTL located on chromosome 6 was reported in various dairy cattle breeds. Nevertheless, the biological mechanism underpinning this QTL has been lacking. Herein, we mapped, fine-mapped, and discovered the putative causal variant underlying this CM resistance QTL in the Dutch dairy cattle population. We identified a ~12 kb multi-allelic copy number variant (CNV), that is in perfect linkage disequilibrium with a lead SNP, as a promising candidate variant. By implementing a fine-mapping and through expression QTL mapping, we showed that the group-specific component gene (GC), a gene encoding a vitamin D binding protein, is an excellent candidate causal gene for the QTL. The multiplicated alleles are associated with increased GC expression and low CM resistance. Ample evidence from functional genomics data supports the presence of an enhancer within this CNV, which would exert cis-regulatory effect on GC. We observed that strong positive selection swept the region near the CNV, and haplotypes associated with the multiplicated allele were strongly selected for. Moreover, the multiplicated allele showed pleiotropic effects for increased milk yield and reduced fertility, hinting that a shared underlying biology for these effects may revolve around the vitamin D pathway. These findings together suggest a putative causal variant of a CM resistance QTL, where a cis-regulatory element located within a CNV can alter gene expression and affect multiple economically important traits.https://doi.org/10.1371/journal.pgen.1009331 |
| spellingShingle | Young-Lim Lee Haruko Takeda Gabriel Costa Monteiro Moreira Latifa Karim Erik Mullaart Wouter Coppieters GplusE consortium Ruth Appeltant Roel F Veerkamp Martien A M Groenen Michel Georges Mirte Bosse Tom Druet Aniek C Bouwman Carole Charlier A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle. PLoS Genetics |
| title | A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle. |
| title_full | A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle. |
| title_fullStr | A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle. |
| title_full_unstemmed | A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle. |
| title_short | A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle. |
| title_sort | 12 kb multi allelic copy number variation encompassing a gc gene enhancer is associated with mastitis resistance in dairy cattle |
| url | https://doi.org/10.1371/journal.pgen.1009331 |
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