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Genome-Wide Analyse...
Genome-Wide Analyses for Osteosarcoma in Leonberger Dogs Reveal the CDKN2A/B Gene Locus as a Major Risk Locus
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Letko, Anna (author)
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Minor, Katie M. (author)
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Norton, Elaine M. (author)
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- Marinescu, Voichita (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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Drögemüller, Michaela (author)
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- Ivansson, Emma (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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- Megquir, Katherine (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Noh, Hyun Ji (author)
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Starkey, Mike (author)
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Friedenberg, Steven G. (author)
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- Lindblad-Toh, Kerstin (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Mickelson, James R. (author)
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Drögemüller, Cord (author)
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(creator_code:org_t)
- 2021-12-09
- 2021
- English.
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In: Genes. - : MDPI. - 2073-4425. ; 12:12
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https://doi.org/10.3...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- Dogs represent a unique spontaneous cancer model. Osteosarcoma (OSA) is the most common primary bone tumor in dogs (OMIA 001441-9615), and strongly resembles human forms of OSA. Several large- to giant-sized dog breeds, including the Leonberger, have a greatly increased risk of developing OSA. We performed genome-wide association analysis with high-density imputed SNP genotype data from 273 Leonberger cases with a median age of 8.1 [3.1-13.5] years and 365 controls older than eight years. This analysis revealed significant associations at the CDKN2A/B gene locus on canine chromosome 11, mirroring previous findings in other dog breeds, such as the greyhound, that also show an elevated risk for OSA. Heritability (h(SNP)(2)) was determined to be 20.6% (SE = 0.08; p-value = 5.7 x 10(-4)) based on a breed prevalence of 20%. The 2563 SNPs across the genome accounted for nearly all the h(SNP)(2) of OSA, with 2183 SNPs of small effect, 316 SNPs of moderate effect, and 64 SNPs of large effect. As with many other cancers it is likely that regulatory, non-coding variants underlie the increased risk for cancer development. Our findings confirm a complex genetic basis of OSA, moderate heritability, and the crucial role of the CDKN2A/B locus leading to strong cancer predisposition in dogs. It will ultimately be interesting to study and compare the known genetic loci associated with canine OSA in human OSA.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- osteosarcoma
- bone cancer
- canis familiaris
- Leonberger
- animal model
- CDKN2A/B
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Letko, Anna
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Minor, Katie M.
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Norton, Elaine M ...
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Marinescu, Voich ...
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Drögemüller, Mic ...
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Ivansson, Emma
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Megquir, Katheri ...
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Noh, Hyun Ji
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Starkey, Mike
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Friedenberg, Ste ...
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Lindblad-Toh, Ke ...
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Mickelson, James ...
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Drögemüller, Cor ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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Uppsala University