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Genome-Wide Analyse...
Genome-Wide Analyses Suggest Mechanisms Involving Early B-cell Development in Canine IgA Deficiency
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- Olsson, Mia (author)
- Karolinska Institutet
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- Tengvall, Katarina, 1980- (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University
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Frankowiack, Marcel (author)
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- Kierczak, Marcin (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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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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- Axelsson, Erik (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Tintle, Linda (author)
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Marti, Eliane (author)
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Roosje, Petra (author)
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Leeb, Tosso (author)
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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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- Hammarström, Lennart (author)
- Karolinska Institutet
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- Lindblad-Toh, Kerstin (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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(creator_code:org_t)
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- 2015-07-30
- 2015
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Abstract
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- Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei) identified 35 genomic loci suggestively associated (p <0.0005) to IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide significantly associated (p <0.0002) with IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- LANTBRUKSVETENSKAPER -- Veterinärmedicin -- Annan veterinärmedicin (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science -- Other Veterinary Science (hsv//eng)
Keyword
- Genome-wide association studies
- Dogs
- IgA
- immunodeficieny
- B-cell
Publication and Content Type
- ref (subject category)
- art (subject category)
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PLOS ONE
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- By the author/editor
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Olsson, Mia
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Tengvall, Katari ...
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Frankowiack, Mar ...
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Kierczak, Marcin
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Bergvall, Kersti ...
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Axelsson, Erik
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show more...
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Tintle, Linda
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Marti, Eliane
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Roosje, Petra
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Leeb, Tosso
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Hedhammar, Åke
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Hammarström, Len ...
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Lindblad-Toh, Ke ...
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show less...
- 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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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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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 ...
- Articles in the publication
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PLOS ONE
- By the university
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Uppsala University
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Karolinska Institutet
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Swedish University of Agricultural Sciences