Home About Browse Search
Svenska


Discovery of a novel pathway for an SLE-related disease complex in the canine breed Nova Scotia duck tolling retriever

Wilbe, Maria (2013). Discovery of a novel pathway for an SLE-related disease complex in the canine breed Nova Scotia duck tolling retriever. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2013:16
ISBN 978-91-576-7773-0
[Doctoral thesis]

[img]
Preview
PDF
2MB

Abstract

The dog is an excellent model to study inherited complex diseases, due to its unique population history and haplotype structure. In this thesis, dogs from the breed Nova Scotia duck tolling retriever (NSDTR) have been used as a model for defining the genetic factors controlling a systemic lupus erythematosus (SLE)-related disorder called immune-mediated rheumatic disease (IMRD) and a steroid responsive meningitis-arteritis (SRMA).

IMRD is characterized by stiffness, mainly after resting, and pain from several joints of extremities and/or muscle pain. The majority of the affected dogs show anti-nuclear antibody (ANA)-positivity that can be divided either into a speckled (ANAS) or homogenous (ANAH) staining pattern. Dogs affected by SRMA display severe neck pain, fever and stiffness and an increased infiltration of immune cells in cerebrospinal fluid in the acute phase of disease. SRMA dogs show a negative ANA result.

We performed a candidate gene study to investigate if dog leukocyte antigen (DLA) class II is associated with the canine SLE-related disease. An increased risk for ANAS dogs was observed for a homozygous risk haplotype and a general homozygosity at DLA class II gives ANAH dogs an increased risk for developing disease.

Genome-wide association mapping identified additional susceptibility loci for the SLE-related disease on canine chromosomes (CFA) 3, 8, 11, 24 and 32. Further analysis revealed that most ANAS dogs homozygous for the DLA risk haplotype also have the genetic risk factors at CFA 11 and 32. Re-sequencing of the five associated regions was performed to identify specific genes and genetic variants involved in the disease.

Expression studies of the candidate genes for ANAS dogs revealed that the PTPN3 (CFA 11) gene is downregulated and that DDIT4L and BANK1 (CFA 32) is upregulated in dogs with the risk haplotype. The identified genes may be important in T-cells, B-cells and possibly macrophages.

This thesis describes the first successful mapping of a complex trait in the dog and shows that MHC class II together with two other identified genetic risk factors contribute to development of systemic autoimmune disease.

Authors/Creators:Wilbe, Maria
Title:Discovery of a novel pathway for an SLE-related disease complex in the canine breed Nova Scotia duck tolling retriever
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2013
Volume:2013:16
Number of Pages:73
Papers/manuscripts:
NumberReferences
I.Wilbe M, Jokinen P, Hermanrud C, Kennedy LJ, Strandberg E, Hansson-Hamlin H, Lohi H, Andersson G (2009). MHC class II polymorphism is associated with a canine SLE-related disease complex. Immunogenetics 61(8): 557-564.
II.Wilbe M, Jokinen P, Truvé K, Seppala EH, Karlsson EK, Biagi T, Hughes A, Bannasch D, Andersson G, Hansson-Hamlin H, Lohi, H, Lindblad-Toh, K (2010). Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nature Genetics 42(3): 250-254.
III.Wilbe M*, Kozyrev SV*, Farias F, Hedlund A, Pielberg G, Gustafson U, Carlborg Ö, Andersson G, Lindblad-Toh K, Hansson-Hamlin H (2013). Risk of rheumatic disease with speckled ANA phenotype in dogs is associated with DLA class II and risk factors on Cfa11 and 32 conferring altered expression of PTPN3, DDIT4L and BANK1. Submitted.
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:978-91-576-7773-0
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
Agrovoc terms:dogs, breeds (animals), lupus erythematosus, arteritis, rheumatism, animal diseases, human diseases, antibodies, immune response, genetic inheritance, genetic maps, animal models
Keywords:dog, systemic lupus erythematosus, antinuclear antibodies, DLA class II, NF-AT, genome-wide association mapping, model organism
URN:NBN:urn:nbn:se:slu:epsilon-e-1236
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-1236
ID Code:10229
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
External funders:FORMAS and Swedish Foundation for Strategic Research and Swedish Research Council
Deposited By: MSc Maria Wilbe
Deposited On:15 Apr 2013 07:14
Metadata Last Modified:02 Dec 2014 10:59

Repository Staff Only: item control page

Downloads

Downloads per year (since September 2012)

View more statistics

Downloads
Hits