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Disease phenotypes in the Obese Strain of chickens
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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(English)Manuscript (preprint) (Other academic)
National Category
Immunology Genetics
Identifiers
URN: urn:nbn:se:uu:diva-182842OAI: oai:DiVA.org:uu-182842DiVA: diva2:561036
Available from: 2012-10-16 Created: 2012-10-16 Last updated: 2012-11-12
In thesis
1. Genetic Characterization of Chicken Models for Autoimmune Disease
Open this publication in new window or tab >>Genetic Characterization of Chicken Models for Autoimmune Disease
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Autoimmune diseases are endemic, but the disease mechanisms are poorly understood. A way to better understand these are to find disease-regulating genes. However, this is difficult as the diseases are complex, with several genes as well as environmental factors influencing the development of disease. A way to facilitate the search for genes responsible for the diseases is to use comparative genomic studies. Animal models are relatively easy to analyze since control of environment and breeding are obtained.

The University of California at Davies – line 200 (UCD-200) chickens have a hereditary disease that is similar to systemic sclerosis. Using a backcross between UCD-200 chickens and red junglefowl (RJF) chickens we identified three loci linked to the disease. The loci contained immune-regulatory genes suggested to be involved in systemic sclerosis in humans, as well as a previously unidentified linkage between systemic sclerosis in UCD-200 chickens and IGFBP3.

The Dark brown (Db) gene enhances red pheomelanin and restricts expression of eumelanin in chickens. The Db phenotype is regulated by an 8 kb deletion upstream of SOX10. Pigmentation studies are potentially useful when trying to identify pathogenic mechanisms and candidate genes in vitiligo

The Obese strain (OS) of chickens spontaneously develops an autoimmune thyroiditis which closely resembles human Hashimoto’s thyroiditis. By using an intercross between OS chickens and RJF chickens, we found several disease phenotypes that can be used in an ongoing linkage analysis with the goal to find candidate genes for autoimmune disease. An important phenotype to record and add to the linkage analysis is autoantibodies against thyroid peroxidase, since this phenotype is a key feature in Hashimoto’s thyroiditis. Previous attempts to measure these titres in OS chickens have failed, hence an assay was developed for this purpose.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 828
Keyword
Autoimmune disease, Hashimoto’s thyroiditis, systemic sclerosis, comparative genomics, linkage analysis, OS chickens, spontaneous autoimmune thyroiditis, UCD-200 chickens.
National Category
Genetics Immunology
Research subject
Molecular Medicine
Identifiers
urn:nbn:se:uu:diva-182843 (URN)978-91-554-8506-1 (ISBN)
Public defence
2012-11-29, Enghoffsalen, Akademiska sjukhuset, Ing. 50, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2012-11-08 Created: 2012-10-16 Last updated: 2013-01-23

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