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dc.contributor.authorLabadie, Julia D.
dc.contributor.authorElvers, Ingegerd
dc.contributor.authorSpencer Feigelson, Heather
dc.contributor.authorMagzamen, Sheryl
dc.contributor.authorYoshimoto, Janna
dc.contributor.authorDossey, Jeremy
dc.contributor.authorBurnett, Robert
dc.contributor.authorAvery, Anne C.
dc.coverage.spatialUnited States
dc.coverage.temporal2013-10-01 – 2015-05-31
dc.date2020
dc.date.accessioned2020-06-18T17:41:49Z
dc.date.available2020-06-18T17:41:49Z
dc.descriptionThis 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.
dc.description.abstractBackground: 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.
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dc.identifier.urihttps://hdl.handle.net/10217/208318
dc.identifier.urihttp://dx.doi.org/10.25675/10217/208318
dc.languageEnglish
dc.publisherColorado State University. Libraries
dc.relation.ispartofData - Colorado State University
dc.relation.isreferencedbyLabadie, 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.subjectlymphoma
dc.subjectleukemia
dc.subjectgenetics
dc.subjectdog
dc.subjectepidemiology
dc.titleDataset associated with "Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors"
dc.typeDataset


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