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Genome-wide associa...
Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors
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- Labadie, Julia D. (författare)
- Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, 1124 Columbia St, Seattle, WA 98104 USA.;Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
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- Elvers, Ingegerd (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Broad Inst MIT & Harvard, Dept Med Biochem & Microbiol, Cambridge, MA USA.;
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- Feigelson, Heather Spencer (författare)
- Kaiser Permanente, Inst Hlth Res, Aurora, CO USA.
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- Magzamen, Sheryl (författare)
- Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
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- Yoshimoto, Janna (författare)
- Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
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- Dossey, Jeremy (författare)
- Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
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- Burnett, Robert (författare)
- Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
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- Avery, Anne C. (författare)
- Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
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Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, 1124 Columbia St, Seattle, WA 98104 USA;Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. Institutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)
- 2020-07-06
- 2020
- Engelska.
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Ingår i: BMC Genomics. - : BMC. - 1471-2164. ; 21:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://bmcgenomics....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 using a genome-wide association study of privately-owned U.S. Golden Retrievers. Results Dogs were categorized as TZL (n = 95), TZUS (n = 142), or control (n = 101) using flow cytometry and genotyped using the Illumina CanineHD BeadChip. Using a mixed linear model adjusting for population stratification, 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 = .3 x 10(- 5)-5.1 x 10(- 5)) near three hyaluronidase genes (SPAM1, HYAL4,andHYALP1). Targeted resequencing of this region using a custom sequence capture array identified missense mutations in all three genes; the variant inSPAM1was 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 = 2.7 x 10(- 7)-7.5 x 10(- 5)) near genes involved in thyroid hormone regulation (DIO2andTSHR). 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Nyckelord
- Lymphoma
- Leukemia
- Genetics
- Dog
- Epidemiology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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