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Unraveling the genetics of lymphocytic thyroiditis using the dog as a model

Sundberg, Katarina (2012). Unraveling the genetics of lymphocytic thyroiditis using the dog as a model. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2012:31
ISBN 978-91-576-7667-2
[Doctoral thesis]

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Abstract

The domestic dog, with its unique genetic structure formed by domestication and recent breed creation, has been proven to be an excellent model for mapping disease genes. In this thesis, we use the dog as a model to investigate the prevalence and genetic background of canine lymphocytic thyroiditis (CLT), one of the most common immune related diseases in dogs. The canine phenotype has been carefully characterized and suggests a strong comparative value to human Hashimoto’s disease because of similar etiology, clinical signs and disease progression. Therefore, our aim was to gain increased knowledge about CLT and its relevance to human autoimmune thyroid disease, to benefit both dogs and humans.

In our first study (paper I) we screened two birth cohorts (3-4 and 6-7 years old, respectively) for elevated serum levels of autoantibodies to thyroglobulin (TgAA) and thyroid stimulating hormone (TSH) and could estimate a very high prevalence of CLT in the giant schnauzer and the hovawart breeds. Next, we aimed at unraveling the genetic background of CLT in the same breeds, using two different approaches; a candidate gene approach followed by a genome-wide association analysis. Using the first approach we obtained evidence that DLA class II polymorphisms can function both as a genetic risk factor predisposing for the disease as well as a protective factor against the disease. Using genome wide association we identified two additional strong susceptibility loci located on chromosome 11 and X. Both regions harbour genes with known immune-regulatory functions and implicates three genes involved in NF-κB pathway. Given the reported role of
NF-κB in many human autoimmune diseases, our results suggest CLT as an excellent genetic model for human thyroiditis.

Authors/Creators:Sundberg, Katarina
Title:Unraveling the genetics of lymphocytic thyroiditis using the dog as a model
Alternative abstract:
LanguageAbstract
SwedishUNSPECIFIED
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2012
Volume:2012:31
Number of Pages:70
Papers/manuscripts:
NumberReferences
IFerm, K., Björnerfeldt, S., Karlsson, Å., Andersson, G., Nachreiner, R. & Hedhammar, A. (2009). Prevalence of diagnostic characteristics indicating canine autoimmune lymphocytic thyroiditis in giant schnauzer and hovawart dogs. J Small Anim Pract 50(4), 176-9.
IISundberg, K., Kamgari, N., Ratnakumar, A., Ahlgren, K.M., Lobell, A., Truvé, K., Strandberg, E., Kämpe, O., Andersson, G., Hedhammar, Å., Pielberg, G., Lindblad-Toh, K. Genome wide-association mapping identifies major susceptibility loci for Canine Lymphocytic Thyroiditis. Manuscript.
IIIWilbe, M., Sundberg, K., Hansen, I.R., Strandberg, E., Nachreiner, R.F., Hedhammar, Å., Kennedy, L.J., Andersson, G. & Björnerfeldt, S. (2010). Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype. Tissue Antigens 75(6), 712-9
Place of Publication:Uppsala
Publisher:Institutionen för husdjursgenetik, Sveriges lantbruksuniversitet
Associated Programs and Other Stakeholders:SLU - Research Areas for the Future > Future Animal Health and Welfare
ISBN for printed version:978-91-576-7667-2
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L10 Animal genetics and breeding
L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Medical Genetics
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Immunology in the medical area
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 402 Animal and Dairy Science > Animal and Dairy Science.
Agrovoc terms:dogs, lymphatic diseases, lymphatic system, genomes, genetic maps
Keywords:Dog, Canine lymphocytic thyroiditis, Hypothyroidism, Genome wide association , Autoimmune, model organism, MHC, DLA, Hashimoto's
URN:NBN:urn:nbn:se:slu:epsilon-e-494
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-494
ID Code:8890
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: Katarina Sundberg
Deposited On:16 May 2012 08:27
Metadata Last Modified:02 Dec 2014 10:50

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