Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle
Abstract Background White spotting of the coat is a characteristic trait of various domestic species including cattle and other mammals. It is a hallmark of Holstein–Friesian cattle, and several previous studies have detected genetic loci with major effects for white spotting in animals with Holstei...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | deu |
| Published: |
BMC
2019-11-01
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| Series: | Genetics Selection Evolution |
| Online Access: | http://link.springer.com/article/10.1186/s12711-019-0506-2 |
| _version_ | 1828752435189907456 |
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| author | Swati Jivanji Gemma Worth Thomas J. Lopdell Anna Yeates Christine Couldrey Edwardo Reynolds Kathryn Tiplady Lorna McNaughton Thomas J. J. Johnson Stephen R. Davis Bevin Harris Richard Spelman Russell G. Snell Dorian Garrick Mathew D. Littlejohn |
| author_facet | Swati Jivanji Gemma Worth Thomas J. Lopdell Anna Yeates Christine Couldrey Edwardo Reynolds Kathryn Tiplady Lorna McNaughton Thomas J. J. Johnson Stephen R. Davis Bevin Harris Richard Spelman Russell G. Snell Dorian Garrick Mathew D. Littlejohn |
| author_sort | Swati Jivanji |
| collection | DOAJ |
| description | Abstract Background White spotting of the coat is a characteristic trait of various domestic species including cattle and other mammals. It is a hallmark of Holstein–Friesian cattle, and several previous studies have detected genetic loci with major effects for white spotting in animals with Holstein–Friesian ancestry. Here, our aim was to better understand the underlying genetic and molecular mechanisms of white spotting, by conducting the largest mapping study for this trait in cattle, to date. Results Using imputed whole-genome sequence data, we conducted a genome-wide association analysis in 2973 mixed-breed cows and bulls. Highly significant quantitative trait loci (QTL) were found on chromosomes 6 and 22, highlighting the well-established coat color genes KIT and MITF as likely responsible for these effects. These results are in broad agreement with previous studies, although we also report a third significant QTL on chromosome 2 that appears to be novel. This signal maps immediately adjacent to the PAX3 gene, which encodes a known transcription factor that controls MITF expression and is the causal locus for white spotting in horses. More detailed examination of these loci revealed a candidate causal mutation in PAX3 (p.Thr424Met), and another candidate mutation (rs209784468) within a conserved element in intron 2 of MITF transcripts expressed in the skin. These analyses also revealed a mechanistic ambiguity at the chromosome 6 locus, where highly dispersed association signals suggested multiple or multiallelic QTL involving KIT and/or other genes in this region. Conclusions Our findings extend those of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes. The sizes of the effects of these QTL are substantial, and could be used to select animals with darker, or conversely whiter, coats depending on the desired characteristics. |
| first_indexed | 2024-12-10T21:08:52Z |
| format | Article |
| id | doaj.art-4182bd4389d749efa8e40b3f86fe123a |
| institution | Directory Open Access Journal |
| issn | 1297-9686 |
| language | deu |
| last_indexed | 2024-12-10T21:08:52Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Genetics Selection Evolution |
| spelling | doaj.art-4182bd4389d749efa8e40b3f86fe123a2022-12-22T01:33:32ZdeuBMCGenetics Selection Evolution1297-96862019-11-0151111810.1186/s12711-019-0506-2Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattleSwati Jivanji0Gemma Worth1Thomas J. Lopdell2Anna Yeates3Christine Couldrey4Edwardo Reynolds5Kathryn Tiplady6Lorna McNaughton7Thomas J. J. Johnson8Stephen R. Davis9Bevin Harris10Richard Spelman11Russell G. Snell12Dorian Garrick13Mathew D. Littlejohn14Massey University ManawatuLivestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)Massey University ManawatuLivestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)Livestock Improvement Corporation (LIC)The University of AucklandMassey University ManawatuLivestock Improvement Corporation (LIC)Abstract Background White spotting of the coat is a characteristic trait of various domestic species including cattle and other mammals. It is a hallmark of Holstein–Friesian cattle, and several previous studies have detected genetic loci with major effects for white spotting in animals with Holstein–Friesian ancestry. Here, our aim was to better understand the underlying genetic and molecular mechanisms of white spotting, by conducting the largest mapping study for this trait in cattle, to date. Results Using imputed whole-genome sequence data, we conducted a genome-wide association analysis in 2973 mixed-breed cows and bulls. Highly significant quantitative trait loci (QTL) were found on chromosomes 6 and 22, highlighting the well-established coat color genes KIT and MITF as likely responsible for these effects. These results are in broad agreement with previous studies, although we also report a third significant QTL on chromosome 2 that appears to be novel. This signal maps immediately adjacent to the PAX3 gene, which encodes a known transcription factor that controls MITF expression and is the causal locus for white spotting in horses. More detailed examination of these loci revealed a candidate causal mutation in PAX3 (p.Thr424Met), and another candidate mutation (rs209784468) within a conserved element in intron 2 of MITF transcripts expressed in the skin. These analyses also revealed a mechanistic ambiguity at the chromosome 6 locus, where highly dispersed association signals suggested multiple or multiallelic QTL involving KIT and/or other genes in this region. Conclusions Our findings extend those of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes. The sizes of the effects of these QTL are substantial, and could be used to select animals with darker, or conversely whiter, coats depending on the desired characteristics.http://link.springer.com/article/10.1186/s12711-019-0506-2 |
| spellingShingle | Swati Jivanji Gemma Worth Thomas J. Lopdell Anna Yeates Christine Couldrey Edwardo Reynolds Kathryn Tiplady Lorna McNaughton Thomas J. J. Johnson Stephen R. Davis Bevin Harris Richard Spelman Russell G. Snell Dorian Garrick Mathew D. Littlejohn Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle Genetics Selection Evolution |
| title | Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle |
| title_full | Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle |
| title_fullStr | Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle |
| title_full_unstemmed | Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle |
| title_short | Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle |
| title_sort | genome wide association analysis reveals qtl and candidate mutations involved in white spotting in cattle |
| url | http://link.springer.com/article/10.1186/s12711-019-0506-2 |
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