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Genome-Wide Analysi...
Genome-Wide Analysis in German Shepherd Dogs Reveals Association of a Locus on CFA 27 with Atopic Dermatitis
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- Tengvall, Katarina (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala University
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- Kierczak, Marcin (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences
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- Bergvall, Kerstin (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences
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- Olsson, Mia (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Frankowiack, Marcel (author)
- Karolinska Institutet
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- Farias, Fabiana H. G. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Pielberg, Gerli (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Carlborg, Örjan (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences,Swedish University of Agricultural Sciences, Uppsala, Sweden
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Leeb, Tosso (author)
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- Andersson, Göran (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics
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- Hammarström, Lennart (author)
- Karolinska Institutet
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- Hedhammar, Åke (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för kliniska vetenskaper (KV),Department of Clinical Sciences
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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, Massachusetts, USA
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(creator_code:org_t)
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- 2013-05-09
- 2013
- English.
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:5, s. e1003475-
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Abstract
Subject headings
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- Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1x10(-5)) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (lambda = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n(cases) = 91, n(controls) = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0x10(-9)), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (p(raw) = 3.1x10(-7), p(genome) = 0.03). The total associated region was defined as a similar to 1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The similar to 209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- LANTBRUKSVETENSKAPER -- Bioteknologi med applikationer på växter och djur -- Genetik och förädling inom lantbruksvetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Agricultural Biotechnology -- Genetics and Breeding in Agricultural Sciences (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Annan veterinärmedicin (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Other Veterinary Science (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Klinisk vetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Clinical Science (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Tengvall, Katari ...
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Kierczak, Marcin
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Bergvall, Kersti ...
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Olsson, Mia
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Frankowiack, Mar ...
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Farias, Fabiana ...
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show more...
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Pielberg, Gerli
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Carlborg, Örjan
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Leeb, Tosso
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Andersson, Göran
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Hammarström, Len ...
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Hedhammar, Åke
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Lindblad-Toh, Ke ...
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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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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Agricultural Bio ...
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and Genetics and Bre ...
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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Veterinary Scien ...
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and Other Veterinary ...
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- AGRICULTURAL SCIENCES
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AGRICULTURAL SCI ...
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and Veterinary Scien ...
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and Clinical Science
- Articles in the publication
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PLOS Genetics
- By the university
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Uppsala University
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Swedish University of Agricultural Sciences
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Karolinska Institutet