Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Risk loci on CFA13 associated with lymphoma in Bullmastiffs (#582)

Sally Mortlock 1 , Mehar S Khatkar 1 , Peter Bennett 1 , Peter Williamson 1
  1. School of Life and Environmental Sciences, Faculty of Veterinary Science, The University of Sydney, Camperdown, NSW, Australia

Limited diversity within dog breeds has resulted in the accumulation of deleterious alleles predisposing breeds to diseases. Lymphoma is the one of the most common malignancies seen in dogs, affecting 1.2% of the population. Research has shown that Bullmastiffs have a high incidence of lymphoma, suggesting a genetic predisposition. The aim of this study was investigate the incidence of lymphoma in the Australian Bullmastiff population and identify risk loci predisposing the breed to lymphoma. Survey data and data analysed from clinical and pathology databases revealed a high incidence of lymphoma in dogs’ ≤6 years. A total of 194 Bullmastiff dogs were genotyped using the 170,000 SNP Illumina CanineHD Beadchip. Information on genetic structure of the population was incorporated into a mixed linear model in GCTA (18 cases, 29 controls) to detect loci associated with lymphoma risk in dogs ≤ 6 years. An association was detected across a 5.4 Mb region on CFA13, 67 SNPs reaching chromosome-wise significance (FDR < 0.05). The region was fine mapped to ~1.2 Mb using both haplotype association and homozygosity analysis. Five risk haplotypes were identified that were significantly associated with lymphoma, 77% of cases were homozygous for risk haplotypes compared to <11% of controls. The associated 1.2 Mb region accounted for over 23% of disease liability in Bullmastiff dogs. One 3’UTR variant and 380 intergentic variants were identified in the associated region using DNA sequence data. Potential functional candidates in the region include MYC, predicted precursor coding regions for miR-1204, miR-1205 and miR-1206 and a region downstream of MYC syntenic to human PVT1, all have ontologies related to cell cycle progression, cell proliferation and cancer. Through our analysis we have identified a region on CFA13 as a risk locus for lymphoma in Bullmastiff dogs. Validation of variants in the CFA13 region is underway and investigation into functional implications.