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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...

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Autores principales: Lee, Young-Lim, Takeda, Haruko, Costa Monteiro Moreira, Gabriel, Karim, Latifa, Mullaart, Erik, Coppieters, Wouter, Appeltant, Ruth, Veerkamp, Roel F., Groenen, Martien A. M., Georges, Michel, Bosse, Mirte, Druet, Tom, Bouwman, Aniek C., Charlier, Carole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328317/
https://www.ncbi.nlm.nih.gov/pubmed/34288907
http://dx.doi.org/10.1371/journal.pgen.1009331
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author Lee, Young-Lim
Takeda, Haruko
Costa Monteiro Moreira, Gabriel
Karim, Latifa
Mullaart, Erik
Coppieters, Wouter
Appeltant, Ruth
Veerkamp, Roel F.
Groenen, Martien A. M.
Georges, Michel
Bosse, Mirte
Druet, Tom
Bouwman, Aniek C.
Charlier, Carole
author_facet Lee, Young-Lim
Takeda, Haruko
Costa Monteiro Moreira, Gabriel
Karim, Latifa
Mullaart, Erik
Coppieters, Wouter
Appeltant, Ruth
Veerkamp, Roel F.
Groenen, Martien A. M.
Georges, Michel
Bosse, Mirte
Druet, Tom
Bouwman, Aniek C.
Charlier, Carole
author_sort Lee, Young-Lim
collection PubMed
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.
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spelling pubmed-83283172021-08-03 A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle Lee, Young-Lim Takeda, Haruko Costa Monteiro Moreira, Gabriel Karim, Latifa Mullaart, Erik Coppieters, Wouter Appeltant, Ruth Veerkamp, Roel F. Groenen, Martien A. M. Georges, Michel Bosse, Mirte Druet, Tom Bouwman, Aniek C. Charlier, Carole PLoS Genet Research Article 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. Public Library of Science 2021-07-21 /pmc/articles/PMC8328317/ /pubmed/34288907 http://dx.doi.org/10.1371/journal.pgen.1009331 Text en © 2021 Lee et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Young-Lim
Takeda, Haruko
Costa Monteiro Moreira, Gabriel
Karim, Latifa
Mullaart, Erik
Coppieters, Wouter
Appeltant, Ruth
Veerkamp, Roel F.
Groenen, Martien A. M.
Georges, Michel
Bosse, Mirte
Druet, Tom
Bouwman, Aniek C.
Charlier, Carole
A 12 kb multi-allelic copy number variation encompassing a GC gene enhancer is associated with mastitis resistance in dairy cattle
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328317/
https://www.ncbi.nlm.nih.gov/pubmed/34288907
http://dx.doi.org/10.1371/journal.pgen.1009331
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