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

PLoS Genet
Authors
Keywords
Abstract

Canine mast cell tumours (CMCT) are one of the most common skin tumours in dogs with a major impact on canine health. Certain breeds have a higher risk of developing mast cell tumours, suggesting that underlying predisposing germ-line genetic factors play a role in the development of this disease. The genetic risk factors are largely unknown, although somatic mutations in the oncogene C-KIT have been detected in a proportion of CMCT, making CMCT a comparative model for mastocytosis in humans where C-KIT mutations are frequent. We have performed a genome wide association study in golden retrievers from two continents and identified separate regions in the genome associated with risk of CMCT in the two populations. Sequence capture of associated regions and subsequent fine mapping in a larger cohort of dogs identified a SNP associated with development of CMCT in the GNAI2 gene (p = 2.2x10-16), introducing an alternative splice form of this gene resulting in a truncated protein. In addition, disease associated haplotypes harbouring the hyaluronidase genes HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14 were identified as separate risk factors in European and US golden retrievers, respectively, suggesting that turnover of hyaluronan plays an important role in the development of CMCT.

Year of Publication
2015
Journal
PLoS Genet
Volume
11
Issue
11
Pages
e1005647
Date Published
2015 Nov
ISSN
1553-7404
URL
DOI
10.1371/journal.pgen.1005647
PubMed ID
26588071
PubMed Central ID
PMC4654484
Links
Grant list
P30 CA016058 / CA / NCI NIH HHS / United States
UL1 TR000090 / TR / NCATS NIH HHS / United States
UL1 TR001070 / TR / NCATS NIH HHS / United States