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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Arendt, Maja Louise
  • Malin Melin
  • Noriko Tonomura
  • Michele Koltookian
  • Celine Courtay-Cahen
  • Netty Flindall
  • Joyce Bass
  • Kim Boerkamp
  • Katherine Megquir
  • Lisa Youell
  • Sue Murphy
  • Colleen McCarthy
  • Cheryl London
  • Gerard R Rutteman
  • Mike Starkey
  • Kerstin Lindblad-Toh

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.

Original languageEnglish
Article numbere1005647
JournalPLOS Genetics
Issue number11
Publication statusPublished - Nov 2015
Externally publishedYes

    Research areas

  • Alternative Splicing, Animals, Dog Diseases/genetics, Dogs, GTP-Binding Protein alpha Subunit, Gi2/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Germ-Line Mutation, Mastocytoma/genetics, Polymorphism, Single Nucleotide

ID: 209172270