Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals
Abstract Background Cohorts of individuals that have been genotyped and phenotyped for genomic selection programs offer the opportunity to better understand genetic variation associated with complex traits. Here, we performed an association study for traits related to body size and muscular developm...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | deu |
| Published: |
BMC
2023-11-01
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| Series: | Genetics Selection Evolution |
| Online Access: | https://doi.org/10.1186/s12711-023-00857-4 |
| _version_ | 1827604529240080384 |
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| author | José Luis Gualdrón Duarte Can Yuan Ann-Stephan Gori Gabriel C. M. Moreira Haruko Takeda Wouter Coppieters Carole Charlier Michel Georges Tom Druet |
| author_facet | José Luis Gualdrón Duarte Can Yuan Ann-Stephan Gori Gabriel C. M. Moreira Haruko Takeda Wouter Coppieters Carole Charlier Michel Georges Tom Druet |
| author_sort | José Luis Gualdrón Duarte |
| collection | DOAJ |
| description | Abstract Background Cohorts of individuals that have been genotyped and phenotyped for genomic selection programs offer the opportunity to better understand genetic variation associated with complex traits. Here, we performed an association study for traits related to body size and muscular development in intensively selected beef cattle. We leveraged multiple trait information to refine and interpret the significant associations. Results After a multiple-step genotype imputation to the sequence-level for 14,762 Belgian Blue beef (BBB) cows, we performed a genome-wide association study (GWAS) for 11 traits related to muscular development and body size. The 37 identified genome-wide significant quantitative trait loci (QTL) could be condensed in 11 unique QTL regions based on their position. Evidence for pleiotropic effects was found in most of these regions (e.g., correlated association signals, overlap between credible sets (CS) of candidate variants). Thus, we applied a multiple-trait approach to combine information from different traits to refine the CS. In several QTL regions, we identified strong candidate genes known to be related to growth and height in other species such as LCORL-NCAPG or CCND2. For some of these genes, relevant candidate variants were identified in the CS, including three new missense variants in EZH2, PAPPA2 and ADAM12, possibly two additional coding variants in LCORL, and candidate regulatory variants linked to CCND2 and ARMC12. Strikingly, four other QTL regions associated with dimension or muscular development traits were related to five (recessive) deleterious coding variants previously identified. Conclusions Our study further supports that a set of common genes controls body size across mammalian species. In particular, we added new genes to the list of those associated with height in both humans and cattle. We also identified new strong candidate causal variants in some of these genes, strengthening the evidence of their causality. Several breed-specific recessive deleterious variants were identified in our QTL regions, probably as a result of the extreme selection for muscular development in BBB cattle. |
| first_indexed | 2024-03-09T06:02:26Z |
| format | Article |
| id | doaj.art-84a9ddc73b7f44418c91378e5aac6cd4 |
| institution | Directory Open Access Journal |
| issn | 1297-9686 |
| language | deu |
| last_indexed | 2024-03-09T06:02:26Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Genetics Selection Evolution |
| spelling | doaj.art-84a9ddc73b7f44418c91378e5aac6cd42023-12-03T12:07:27ZdeuBMCGenetics Selection Evolution1297-96862023-11-0155111710.1186/s12711-023-00857-4Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammalsJosé Luis Gualdrón Duarte0Can Yuan1Ann-Stephan Gori2Gabriel C. M. Moreira3Haruko Takeda4Wouter Coppieters5Carole Charlier6Michel Georges7Tom Druet8Unit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of LiègeUnit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of LiègeWalloon Breeders AssociationUnit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of LiègeUnit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of LiègeGIGA Genomic Platform, GIGA-R, University of LiègeUnit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of LiègeUnit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of LiègeUnit of Animal Genomics, GIGA-R & Faculty of Veterinary Medicine, University of LiègeAbstract Background Cohorts of individuals that have been genotyped and phenotyped for genomic selection programs offer the opportunity to better understand genetic variation associated with complex traits. Here, we performed an association study for traits related to body size and muscular development in intensively selected beef cattle. We leveraged multiple trait information to refine and interpret the significant associations. Results After a multiple-step genotype imputation to the sequence-level for 14,762 Belgian Blue beef (BBB) cows, we performed a genome-wide association study (GWAS) for 11 traits related to muscular development and body size. The 37 identified genome-wide significant quantitative trait loci (QTL) could be condensed in 11 unique QTL regions based on their position. Evidence for pleiotropic effects was found in most of these regions (e.g., correlated association signals, overlap between credible sets (CS) of candidate variants). Thus, we applied a multiple-trait approach to combine information from different traits to refine the CS. In several QTL regions, we identified strong candidate genes known to be related to growth and height in other species such as LCORL-NCAPG or CCND2. For some of these genes, relevant candidate variants were identified in the CS, including three new missense variants in EZH2, PAPPA2 and ADAM12, possibly two additional coding variants in LCORL, and candidate regulatory variants linked to CCND2 and ARMC12. Strikingly, four other QTL regions associated with dimension or muscular development traits were related to five (recessive) deleterious coding variants previously identified. Conclusions Our study further supports that a set of common genes controls body size across mammalian species. In particular, we added new genes to the list of those associated with height in both humans and cattle. We also identified new strong candidate causal variants in some of these genes, strengthening the evidence of their causality. Several breed-specific recessive deleterious variants were identified in our QTL regions, probably as a result of the extreme selection for muscular development in BBB cattle.https://doi.org/10.1186/s12711-023-00857-4 |
| spellingShingle | José Luis Gualdrón Duarte Can Yuan Ann-Stephan Gori Gabriel C. M. Moreira Haruko Takeda Wouter Coppieters Carole Charlier Michel Georges Tom Druet Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals Genetics Selection Evolution |
| title | Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals |
| title_full | Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals |
| title_fullStr | Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals |
| title_full_unstemmed | Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals |
| title_short | Sequenced-based GWAS for linear classification traits in Belgian Blue beef cattle reveals new coding variants in genes regulating body size in mammals |
| title_sort | sequenced based gwas for linear classification traits in belgian blue beef cattle reveals new coding variants in genes regulating body size in mammals |
| url | https://doi.org/10.1186/s12711-023-00857-4 |
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