Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horses
<p>Abstract</p> <p>Background</p> <p>Greying with age in horses is an autosomal dominant trait, associated with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We recently identified a 4.6 kb duplication in <it>STX17</it> to be associat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-08-01
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| Series: | BMC Genomics |
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| Online Access: | http://www.biomedcentral.com/1471-2164/13/365 |
| _version_ | 1818524605768269824 |
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| author | Sundström Elisabeth Imsland Freyja Mikko Sofia Wade Claire Sigurdsson Snaevar Pielberg Gerli Golovko Anna Curik Ino Seltenhammer Monika H Sölkner Johann Lindblad-Toh Kerstin Andersson Leif |
| author_facet | Sundström Elisabeth Imsland Freyja Mikko Sofia Wade Claire Sigurdsson Snaevar Pielberg Gerli Golovko Anna Curik Ino Seltenhammer Monika H Sölkner Johann Lindblad-Toh Kerstin Andersson Leif |
| author_sort | Sundström Elisabeth |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Greying with age in horses is an autosomal dominant trait, associated with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We recently identified a 4.6 kb duplication in <it>STX17</it> to be associated with the phenotype. The aims of this study were to investigate if the duplication in Grey horses shows copy number variation and to exclude that any other polymorphism is uniquely associated with the <it>Grey</it> mutation.</p> <p>Results</p> <p>We found little evidence for copy number expansion of the duplicated sequence in blood DNA from Grey horses. In contrast, clear evidence for copy number expansions was indicated in five out of eight tested melanoma tissues or melanoma cell lines. A tendency of a higher copy number in aggressive tumours was also found. Massively parallel resequencing of the ~350 kb Grey haplotype did not reveal any additional mutations perfectly associated with the phenotype, confirming the duplication as the true causative mutation. We identified three SNP alleles that were present in a subset of Grey haplotypes within the 350 kb region that shows complete linkage disequilibrium with the causative mutation. Thus, these three nucleotide substitutions must have occurred subsequent to the duplication, consistent with our interpretation that the Grey mutation arose more than 2,000 years before present.</p> <p>Conclusions</p> <p>These results suggest that the mutation acts as a melanoma-driving regulatory element. The elucidation of the mechanistic features of the duplication will be of considerable interest for the characterization of these horse melanomas as well as for the field of human melanoma research.</p> |
| first_indexed | 2024-12-11T05:59:16Z |
| format | Article |
| id | doaj.art-b9b409ab83a34762b92c5e84199b3add |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-11T05:59:16Z |
| publishDate | 2012-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-b9b409ab83a34762b92c5e84199b3add2022-12-22T01:18:34ZengBMCBMC Genomics1471-21642012-08-0113136510.1186/1471-2164-13-365Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horsesSundström ElisabethImsland FreyjaMikko SofiaWade ClaireSigurdsson SnaevarPielberg GerliGolovko AnnaCurik InoSeltenhammer Monika HSölkner JohannLindblad-Toh KerstinAndersson Leif<p>Abstract</p> <p>Background</p> <p>Greying with age in horses is an autosomal dominant trait, associated with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We recently identified a 4.6 kb duplication in <it>STX17</it> to be associated with the phenotype. The aims of this study were to investigate if the duplication in Grey horses shows copy number variation and to exclude that any other polymorphism is uniquely associated with the <it>Grey</it> mutation.</p> <p>Results</p> <p>We found little evidence for copy number expansion of the duplicated sequence in blood DNA from Grey horses. In contrast, clear evidence for copy number expansions was indicated in five out of eight tested melanoma tissues or melanoma cell lines. A tendency of a higher copy number in aggressive tumours was also found. Massively parallel resequencing of the ~350 kb Grey haplotype did not reveal any additional mutations perfectly associated with the phenotype, confirming the duplication as the true causative mutation. We identified three SNP alleles that were present in a subset of Grey haplotypes within the 350 kb region that shows complete linkage disequilibrium with the causative mutation. Thus, these three nucleotide substitutions must have occurred subsequent to the duplication, consistent with our interpretation that the Grey mutation arose more than 2,000 years before present.</p> <p>Conclusions</p> <p>These results suggest that the mutation acts as a melanoma-driving regulatory element. The elucidation of the mechanistic features of the duplication will be of considerable interest for the characterization of these horse melanomas as well as for the field of human melanoma research.</p>http://www.biomedcentral.com/1471-2164/13/365<it>STX17</it>MelanomaHair greyingCopy number variationMelanocytes |
| spellingShingle | Sundström Elisabeth Imsland Freyja Mikko Sofia Wade Claire Sigurdsson Snaevar Pielberg Gerli Golovko Anna Curik Ino Seltenhammer Monika H Sölkner Johann Lindblad-Toh Kerstin Andersson Leif Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horses BMC Genomics <it>STX17</it> Melanoma Hair greying Copy number variation Melanocytes |
| title | Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horses |
| title_full | Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horses |
| title_fullStr | Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horses |
| title_full_unstemmed | Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horses |
| title_short | Copy number expansion of the <it>STX17</it> duplication in melanoma tissue from Grey horses |
| title_sort | copy number expansion of the it stx17 it duplication in melanoma tissue from grey horses |
| topic | <it>STX17</it> Melanoma Hair greying Copy number variation Melanocytes |
| url | http://www.biomedcentral.com/1471-2164/13/365 |
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