Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers

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To shed light on the genetic predisposition to cancers of the hematologic system, we performed genome-wide association analysis of affected and non-affected pet dogs. Dogs naturally develop the same diseases as humans, including cancer, and the relatively limited genetic diversity within different breeds makes genetic studies easier compared to in humans. By doing genome-wide association, we identified loci predisposing to hemangiosarcoma and B-cell lymphoma. To our surprise, we found two shared loci predisposing to both diseases. Within these two regions we identified several partially overlapping haplotypes, predisposing somewhat differently to the two cancers. We found no coding mutations that followed the risk or non-risk haplotypes suggesting that regulatory mutations exert the effect on disease. We also looked at gene expression in B-cell lymphomas, comparing samples from individuals with risk or non-risk haplotypes. This analysis showed differential expression associated with the haplotypes at both loci, suggesting the risk haplotypes are associated with an effect on T-cell response.

Vyšlo v časopise: Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1004922
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004922

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