NIH Research Festival
Histiocytic Sarcoma (HS) is a rare human hematopoietic neoplasm that accounts for less than 1% of hematolymphoid cancers and is usually fatal. Its genetic etiology has therefore been difficult to establish. HS in dogs, by comparison, shows strong breed specificity with 25% of Bernese mountain dogs (BMD) developing the disease in their lifetime. Therefore, the domestic dog represents a unique system in which to investigate the genetic predispositions of HS. Our lab has previously undertaken genome wide association studies (GWAS) on both American and European BMD. Both American and European BMD demonstrated evidence for a significant locus on canine chromosome (CFA) 11; fine mapping revealed a single haplotype spanning the MTAP gene and part of the CDKN2A gene in 96% of cases. GWAS in European BMD, however, also showed a significant locus on CFA14. I have since undertaken targeted resequencing of the CFA14 locus in a subset of European BMD and identified 34,000 variants with many in promising candidate genes. I am performing PCR-based sequencing of a larger subset of 24 European BMD HS cases and 24 controls to elucidate a risk haplotype for HS for this population. Further, the laboratory has generated a 30x sequence from one HS case and is generating a second one from the European BMD population. I am working to include that detailed information in my analysis to find a disease-associated haplotype that I can test in our larger collection of 572 BMD cases and 615 controls that may point out factors involved in HS.
Scientific Focus Area: Genetics and Genomics
This page was last updated on Friday, March 26, 2021