Dataset associated with "Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors"
| dc.contributor.author | Labadie, Julia D. | |
| dc.contributor.author | Elvers, Ingegerd | |
| dc.contributor.author | Spencer Feigelson, Heather | |
| dc.contributor.author | Magzamen, Sheryl | |
| dc.contributor.author | Yoshimoto, Janna | |
| dc.contributor.author | Dossey, Jeremy | |
| dc.contributor.author | Burnett, Robert | |
| dc.contributor.author | Avery, Anne C. | |
| dc.coverage.spatial | United States | en_US |
| dc.coverage.temporal | 2013-10-01 – 2015-05-31 | en_US |
| dc.date.accessioned | 2020-06-18T17:41:49Z | |
| dc.date.available | 2020-06-18T17:41:49Z | |
| dc.date.issued | 2020 | |
| dc.description | This dataset includes genotyping data for 267 US Golden Retrievers, obtained under CSU IACUC Protocol #13-4473A. Samples were recruited from the privately-owned pet population from October 2013 – May 2015 as part of a larger case-control study with the goal of understanding genetic and environmental risk factors for T zone Lymphoma. Blood samples were genotyped using the Illumina CanineHD BeadChip. Dogs were categorized as case, TZUS, or control. The list of individuals provided has undergone quality control filtering, including: 1) removing dogs with call rates <97.5%, 2) removing dogs of European origin, and 3) removing highly related individuals (half-sibling or closer). For our analysis, we additionally did QC on the SNP dataset, including removing SNPs with call rates <97.5 or minor allele frequency <5%. However, the .bed and .bim files provided are unfiltered. | en_US |
| dc.description | College of Veterinary Medicine and Biomedical Sciences | |
| dc.description | Department of Environmental and Radiological Health Sciences | |
| dc.description | Department of Microbiology, Immunology, and Pathology | |
| dc.description.abstract | Background: T zone lymphoma (TZL), a histologic variant of peripheral T cell lymphoma, represents about 12% of all canine lymphomas. Golden Retrievers appear predisposed, representing over 40% of TZL cases. Prior research found that asymptomatic aged Golden Retrievers frequently have populations of T zone-like cells (phenotypically identical to TZL) of undetermined significance (TZUS), potentially representing a pre-clinical state. These findings suggest a genetic risk factor for this disease and caused us to investigate potential genes of interest. Methods: Privately-owned U.S. Golden Retrievers were categorized as TZL (n=95), TZUS (n=142), or control (n=101) using flow cytometry and genotyped using the Illumina CanineHD BeadChip. Single nucleotide polymorphism (SNP)-specific associations were evaluated using a mixed linear model adjusting for population stratification. Associated regions were subsequently sequenced using a custom sequence capture array (NimbleGen SeqCap EZ Developer Kit) on an Illumina NextSeq 500. Results: We found association with genome-wide significance in regions on chromosomes 8 and 14. The chromosome 14 peak included four SNPs (Odds Ratio=1.18–1.19, p=.3x10-5–5.1x10-5) near three hyaluronidase genes (SPAM1, HYAL4, and HYALP1). Targeted resequencing of this region identified missense mutations in all three genes; the variant in SPAM1 was predicted to be damaging. These mutations were also associated with risk for mast cell tumors among Golden Retrievers in an unrelated study. The chromosome 8 peak contained 7 SNPs (Odds Ratio=1.24–1.42, p= 2.7x10-7–7.5x10-5) near genes involved in thyroid hormone regulation (DIO2 and TSHR). A prior study from our laboratory found hypothyroidism is inversely associated with TZL risk. No coding mutations were found with targeted resequencing but identified variants may play a regulatory role for all or some of the genes. Conclusions: The pathogenesis of canine TZL may be related to hyaluronan breakdown and subsequent production of pro-inflammatory and pro-oncogenic byproducts. The association on chromosome 8 may indicate thyroid hormone is involved in TZL development, consistent with findings from a previous study evaluating epidemiologic risk factors for TZL. Future work is needed to elucidate these mechanisms. | en_US |
| dc.format.medium | ZIP | |
| dc.format.medium | TXT | |
| dc.format.medium | CSV | |
| dc.format.medium | PLINK | |
| dc.identifier.uri | https://hdl.handle.net/10217/208318 | |
| dc.identifier.uri | http://dx.doi.org/10.25675/10217/208318 | |
| dc.language | English | en_US |
| dc.language.iso | eng | en_US |
| dc.publisher | Colorado State University. Libraries | en_US |
| dc.relation.ispartof | Research Data | |
| dc.relation.isreferencedby | Labadie, J.D., Elvers, I., Feigelson, H.S. et al. Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors. BMC Genomics 21, 464 (2020). https://doi.org/10.1186/s12864-020-06872-9 | |
| dc.subject | lymphoma | |
| dc.subject | leukemia | |
| dc.subject | genetics | |
| dc.subject | dog | |
| dc.subject | epidemiology | |
| dc.title | Dataset associated with "Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors" | en_US |
| dc.type | Dataset | en_US |