A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines
Abstract Background Genome-wide association studies (GWAS) aim at identifying genomic regions involved in phenotype expression, but identifying causative variants is difficult. Pig Combined Annotation Dependent Depletion (pCADD) scores provide a measure of the predicted consequences of genetic varia...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | deu |
| Published: |
BMC
2023-06-01
|
| Series: | Genetics Selection Evolution |
| Online Access: | https://doi.org/10.1186/s12711-023-00815-0 |
| _version_ | 1797801637717213184 |
|---|---|
| author | Suzanne Desire Martin Johnsson Roger Ros-Freixedes Ching-Yi Chen Justin W. Holl William O. Herring Gregor Gorjanc Richard J. Mellanby John M. Hickey Melissa K. Jungnickel |
| author_facet | Suzanne Desire Martin Johnsson Roger Ros-Freixedes Ching-Yi Chen Justin W. Holl William O. Herring Gregor Gorjanc Richard J. Mellanby John M. Hickey Melissa K. Jungnickel |
| author_sort | Suzanne Desire |
| collection | DOAJ |
| description | Abstract Background Genome-wide association studies (GWAS) aim at identifying genomic regions involved in phenotype expression, but identifying causative variants is difficult. Pig Combined Annotation Dependent Depletion (pCADD) scores provide a measure of the predicted consequences of genetic variants. Incorporating pCADD into the GWAS pipeline may help their identification. Our objective was to identify genomic regions associated with loin depth and muscle pH, and identify regions of interest for fine-mapping and further experimental work. Genotypes for ~ 40,000 single nucleotide morphisms (SNPs) were used to perform GWAS for these two traits, using de-regressed breeding values (dEBV) for 329,964 pigs from four commercial lines. Imputed sequence data was used to identify SNPs in strong ( $$\ge$$ ≥ 0.80) linkage disequilibrium with lead GWAS SNPs with the highest pCADD scores. Results Fifteen distinct regions were associated with loin depth and one with loin pH at genome-wide significance. Regions on chromosomes 1, 2, 5, 7, and 16, explained between 0.06 and 3.55% of the additive genetic variance and were strongly associated with loin depth. Only a small part of the additive genetic variance in muscle pH was attributed to SNPs. The results of our pCADD analysis suggests that high-scoring pCADD variants are enriched for missense mutations. Two close but distinct regions on SSC1 were associated with loin depth, and pCADD identified the previously identified missense variant within the MC4R gene for one of the lines. For loin pH, pCADD identified a synonymous variant in the RNF25 gene (SSC15) as the most likely candidate for the muscle pH association. The missense mutation in the PRKAG3 gene known to affect glycogen content was not prioritised by pCADD for loin pH. Conclusions For loin depth, we identified several strong candidate regions for further statistical fine-mapping that are supported in the literature, and two novel regions. For loin muscle pH, we identified one previously identified associated region. We found mixed evidence for the utility of pCADD as an extension of heuristic fine-mapping. The next step is to perform more sophisticated fine-mapping and expression quantitative trait loci (eQTL) analysis, and then interrogate candidate variants in vitro by perturbation-CRISPR assays. |
| first_indexed | 2024-03-13T04:53:30Z |
| format | Article |
| id | doaj.art-6256dd90e214432991a89312e92ec1cc |
| institution | Directory Open Access Journal |
| issn | 1297-9686 |
| language | deu |
| last_indexed | 2024-03-13T04:53:30Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Genetics Selection Evolution |
| spelling | doaj.art-6256dd90e214432991a89312e92ec1cc2023-06-18T11:03:52ZdeuBMCGenetics Selection Evolution1297-96862023-06-0155111310.1186/s12711-023-00815-0A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred linesSuzanne Desire0Martin Johnsson1Roger Ros-Freixedes2Ching-Yi Chen3Justin W. Holl4William O. Herring5Gregor Gorjanc6Richard J. Mellanby7John M. Hickey8Melissa K. Jungnickel9The Roslin Institute, The University of EdinburghSwedish University of Agricultural SciencesDepartament de Ciència Animal, Universitat de Lleida-Agrotecnio-CERCA CenterThe Pig Improvement Company, Genus PlcThe Pig Improvement Company, Genus PlcThe Pig Improvement Company, Genus PlcThe Roslin Institute, The University of EdinburghThe Royal (Dick) School of Veterinary Studies, The University of EdinburghThe Roslin Institute, The University of EdinburghThe Roslin Institute, The University of EdinburghAbstract Background Genome-wide association studies (GWAS) aim at identifying genomic regions involved in phenotype expression, but identifying causative variants is difficult. Pig Combined Annotation Dependent Depletion (pCADD) scores provide a measure of the predicted consequences of genetic variants. Incorporating pCADD into the GWAS pipeline may help their identification. Our objective was to identify genomic regions associated with loin depth and muscle pH, and identify regions of interest for fine-mapping and further experimental work. Genotypes for ~ 40,000 single nucleotide morphisms (SNPs) were used to perform GWAS for these two traits, using de-regressed breeding values (dEBV) for 329,964 pigs from four commercial lines. Imputed sequence data was used to identify SNPs in strong ( $$\ge$$ ≥ 0.80) linkage disequilibrium with lead GWAS SNPs with the highest pCADD scores. Results Fifteen distinct regions were associated with loin depth and one with loin pH at genome-wide significance. Regions on chromosomes 1, 2, 5, 7, and 16, explained between 0.06 and 3.55% of the additive genetic variance and were strongly associated with loin depth. Only a small part of the additive genetic variance in muscle pH was attributed to SNPs. The results of our pCADD analysis suggests that high-scoring pCADD variants are enriched for missense mutations. Two close but distinct regions on SSC1 were associated with loin depth, and pCADD identified the previously identified missense variant within the MC4R gene for one of the lines. For loin pH, pCADD identified a synonymous variant in the RNF25 gene (SSC15) as the most likely candidate for the muscle pH association. The missense mutation in the PRKAG3 gene known to affect glycogen content was not prioritised by pCADD for loin pH. Conclusions For loin depth, we identified several strong candidate regions for further statistical fine-mapping that are supported in the literature, and two novel regions. For loin muscle pH, we identified one previously identified associated region. We found mixed evidence for the utility of pCADD as an extension of heuristic fine-mapping. The next step is to perform more sophisticated fine-mapping and expression quantitative trait loci (eQTL) analysis, and then interrogate candidate variants in vitro by perturbation-CRISPR assays.https://doi.org/10.1186/s12711-023-00815-0 |
| spellingShingle | Suzanne Desire Martin Johnsson Roger Ros-Freixedes Ching-Yi Chen Justin W. Holl William O. Herring Gregor Gorjanc Richard J. Mellanby John M. Hickey Melissa K. Jungnickel A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines Genetics Selection Evolution |
| title | A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines |
| title_full | A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines |
| title_fullStr | A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines |
| title_full_unstemmed | A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines |
| title_short | A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines |
| title_sort | genome wide association study for loin depth and muscle ph in pigs from intensely selected purebred lines |
| url | https://doi.org/10.1186/s12711-023-00815-0 |
| work_keys_str_mv | AT suzannedesire agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT martinjohnsson agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT rogerrosfreixedes agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT chingyichen agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT justinwholl agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT williamoherring agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT gregorgorjanc agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT richardjmellanby agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT johnmhickey agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT melissakjungnickel agenomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT suzannedesire genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT martinjohnsson genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT rogerrosfreixedes genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT chingyichen genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT justinwholl genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT williamoherring genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT gregorgorjanc genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT richardjmellanby genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT johnmhickey genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines AT melissakjungnickel genomewideassociationstudyforloindepthandmusclephinpigsfromintenselyselectedpurebredlines |