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Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours


Pet dogs develop many of the same diseases as humans. Hence, studying diseases in dogs can be valuable for learning about human conditions. The genetic structure caused by inbreeding within dog breeds has proven to be advantageous to map genetic diseases. Golden retrievers have a very high risk of developing mast cell tumours suggesting that there is a genetic background for this disease. In the present study we investigated genetic risk factors for this disease in golden retrievers. We identified three regions of the genome predisposing to the development of mast cell tumors. A candidate mutation in the GNAI2 gene was found to change the form of this gene. The disease associated regions also harbour multiple hyaluronidase genes (HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14) suggesting that turnover of hyaluronic acid plays an important role in the development of CMCT. Human mastocytosis shares many characteristics with canine mast cell tumours and we believe our findings can help clarifying the biology behind this disease in humans as well as identifying new therapeutic targets.


Vyšlo v časopise: Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005647
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005647

Souhrn

Pet dogs develop many of the same diseases as humans. Hence, studying diseases in dogs can be valuable for learning about human conditions. The genetic structure caused by inbreeding within dog breeds has proven to be advantageous to map genetic diseases. Golden retrievers have a very high risk of developing mast cell tumours suggesting that there is a genetic background for this disease. In the present study we investigated genetic risk factors for this disease in golden retrievers. We identified three regions of the genome predisposing to the development of mast cell tumors. A candidate mutation in the GNAI2 gene was found to change the form of this gene. The disease associated regions also harbour multiple hyaluronidase genes (HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14) suggesting that turnover of hyaluronic acid plays an important role in the development of CMCT. Human mastocytosis shares many characteristics with canine mast cell tumours and we believe our findings can help clarifying the biology behind this disease in humans as well as identifying new therapeutic targets.


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