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A microarray system for genotyping 150 single nucleotide polymorphisms in the coding region of human mitochondrial DNA
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
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2006 (English)In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 87, no 4, 534-542 p.Article in journal (Refereed) Published
Abstract [en]

We established a genotyping system for a panel of 150 SNPs in the coding regions of mitochondrial DNA based on multiplex tag-array minisequencing. We show the feasibility of this system for simultaneous identification of individuals and prediction of the geographical origin of the mitochondrial DNA population lineage of the sample donors by genotyping the panel of SNPs in 265 samples representing nine different populations from Africa, Europe, and Asia. Nearly 40,000 genotypes were produced in the study, with an overall genotyping success rate of 95% and accuracy close to 100%. The gene diversity value of the panel of 150 SNPs was 0.991, compared to 0.995 for sequencing 500 nucleotides of the hypervariable regions I and II of mtDNA. For 17 individuals with identical sequences in the hypervariable regions of mtDNA, our panel of SNPs increased the power of discrimination. We observed 144 haplotypes that correspond to previously determined mitochondrial “haplogroups,” and they allowed prediction of the origin of the maternal population lineage of 97% of the analyzed samples.

Place, publisher, year, edition, pages
2006. Vol. 87, no 4, 534-542 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-94314DOI: 10.1016/j.ygeno.2005.11.022PubMedID: 16406725OAI: oai:DiVA.org:uu-94314DiVA: diva2:168123
Available from: 2006-04-20 Created: 2006-04-20 Last updated: 2012-04-13Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 138
Molecular medicine, Minisequencing, SNP, Microarray, Polymorphism, Mitochondria, Systemic Lupus Erythematosus, Rheumatoid Arthritis, Association study, Type I interferon, Genotyping, Molekylärmedicin
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
Available from: 2006-04-20 Created: 2006-04-20Bibliographically approved

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Syvänen, Ann-Christine
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