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Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
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2005 In: American Journal of Human Genetics, ISSN 0002-9297, Vol. 76, no 3, 528-37 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 76, no 3, 528-37 p.
Identifiers
URN: urn:nbn:se:uu:diva-94315OAI: oai:DiVA.org:uu-94315DiVA: diva2:168124
Available from: 2006-04-20 Created: 2006-04-20Bibliographically approved
In thesis
1. Large-Scale Genotyping for Analysis of the Type I Interferon System in Autoimmune Diseases
Open this publication in new window or tab >>Large-Scale Genotyping for Analysis of the Type I Interferon System in Autoimmune Diseases
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation. We developed a novel multiplexed method for SNP genotyping based on four-color fluorophore tag-microarray minisequencing. This method allows simultaneous genotyping of 80 samples and up to 200 SNPs in any allele combination. In study I we set up the method for a panel of SNPs from genes in the type I interferon system, and applied it in study III. In study II we used the technique to genotype SNPs from the coding region of the mitochondrial genome. A panel of 150 SNPs was genotyped in 265 individuals representing nine different populations. We demonstrated that the multiplexed SNP genotyping method for mitochondrial DNA increases the power of forensic identification in combination with sequencing of the hypervariable region of mitochondrial DNA.

In study III we performed a genetic association study of SNPs in genes related to the type I Interferon system in Systemic Lupus Erythematosus (SLE). SLE is a chronic autoimmune inflammatory disease with a complex etiology. The SNPs were genotyped in DNA samples from Swedish, Finnish, and Icelandic patients with SLE, unaffected family members, and unrelated controls. The analysis identified SNPs in two genes, the tyrosine kinase 2 (TYK2) and interferon regulatory factor 5 (IRF5) genes that are highly associated with SLE with p-values <10-7 for joint linkage and association.

Study IV describes the analysis of the TYK2 and IRF5 SNPs in a large Rheumatoid Arthritis (RA) sample cohort. We found that SNPs in the IRF5 gene were significantly associated with RA with a p-value = 0.00008. In contrast, we did not detect an association with SNPs in the TYK2 gene. These findings demonstrate that SLE and RA may have a common genetic background in the case of IRF5, while the TYK2 variants appear to be unique for SLE.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 82 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 138
Keyword
Molecular medicine, Minisequencing, SNP, Microarray, Polymorphism, Mitochondria, Systemic Lupus Erythematosus, Rheumatoid Arthritis, Association study, Type I interferon, Genotyping, Molekylärmedicin
Identifiers
urn:nbn:se:uu:diva-6792 (URN)91-554-6532-3 (ISBN)
Public defence
2006-05-11, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjöldsväg 20, Uppsala, 13:15
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Available from: 2006-04-20 Created: 2006-04-20Bibliographically approved

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