Lymphoma in Border Collies: Genome-Wide Association and Pedigree Analysis

SIMPLE SUMMARY: Lymphoma is a common cancer in dogs, with large variation between breeds in both the incidence and frequency of immunophenotypes (B-cell or T-cell lymphoma). Very few studies have explored the genetic underpinnings of lymphoma in dogs, and it is not known whether various breeds share common risk genes considering the disparities in disease occurrence and immunophenotype distribution. In this study, our aim was to investigate lymphoma in a population of Border Collies, a breed at increased risk of lymphoma (often B-cell type). To our knowledge, this is the first genetic investigation of lymphoma risk in Border Collies. We examined pedigree data for possible inheritance patterns, and conducted a genetic investigation that incorporated the pedigree information to uncover possible genetic predispositions for lymphoma. We identified regions on chromosomes 18 and 27 that harbour cancer-related genes as prime candidates for lymphoma susceptibility, warranting further investigation. ABSTRACT: There has been considerable interest in studying cancer in dogs and its potential as a model system for humans. One area of research has been the search for genetic risk variants in canine lymphoma, which is amongst the most common canine cancers. Previous studies have focused on a limited number of breeds, but none have included Border Collies. The aims of this study were to identify relationships between Border Collie lymphoma cases through an extensive pedigree investigation and to utilise relationship information to conduct genome-wide association study (GWAS) analyses to identify risk regions associated with lymphoma. The expanded pedigree analysis included 83,000 Border Collies, with 71 identified lymphoma cases. The analysis identified affected close relatives, and a common ancestor was identified for 54 cases. For the genomic study, a GWAS was designed to incorporate lymphoma cases, putative “carriers”, and controls. A case-control GWAS was also conducted as a comparison. Both analyses showed significant SNPs in regions on chromosomes 18 and 27. Putative top candidate genes from these regions included DLA-79, WNT10B, LMBR1L, KMT2D, and CCNT1.