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dc.contributor.authorMonsuur, Alienke J.
dc.contributor.authorZhernakova, Alexandra
dc.contributor.authorPinto, Dalila
dc.contributor.authorVerduijn, Willem
dc.contributor.authorRomanos, Jihane
dc.contributor.authorAuricchio, Renata
dc.contributor.authorLopez, Ana
dc.contributor.authorvan Heel, David A.
dc.contributor.authorCrusius, J. Bart A
dc.contributor.authorWijmenga, Cisca
dc.contributor.authorde Bakker, Paul I Wen
dc.date.accessioned2011-11-09T16:56:37Z
dc.date.issued2008
dc.identifier.citationMonsuur, Alienke J., Paul I. W. de Bakker, Alexandra Zhernakova, Dalila Pinto, Willem Verduijn, Jihane Romanos, Renata Auricchio, et al. 2008. Effective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphisms. PLoS ONE 3(5): e2270.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5343417
dc.description.abstractBackground: The HLA genes, located in the MHC region on chromosome 6p21.3, play an important role in many autoimmune disorders, such as celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis, multiple sclerosis, psoriasis and others. Known HLA variants that confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and DQA1*03/DQB1*0302 (DQ8). To diagnose the majority of CD patients and to study disease susceptibility and progression, typing these strongly associated HLA risk factors is of utmost importance. However, current genotyping methods for HLA risk factors involve many reactions, and are complicated and expensive. We sought a simple experimental approach using tagging SNPs that predict the CD-associated HLA risk factors. Methodology: Our tagging approach exploits linkage disequilibrium between single nucleotide polymorphism (SNPs) and the CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7) that attribute to the risk of DQ2.5 to CD. To evaluate the predictive power of this approach, we performed an empirical comparison of the predicted DQ types, based on these six tag SNPs, with those executed with current validated laboratory typing methods of the HLA-DQA1 and -DQB1 genes in three large cohorts. The results were validated in three European celiac populations. Conclusion: Using this method, only six SNPs were needed to predict the risk types carried by >95% of CD patients. We determined that for this tagging approach the sensitivity was >0.991, specificity >0.996 and the predictive value >0.948. Our results show that this tag SNP method is very accurate and provides an excellent basis for population screening for CD. This method is broadly applicable in European populations.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0002270en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386975/pdf/en_US
dash.licenseLAA
dc.subjectgenetics and genomicsen_US
dc.subjectcomplex traitsen_US
dc.subjectimmunologyen_US
dc.subjectautoimmunityen_US
dc.subjectgastroenterology and hepatologyen_US
dc.subjectsmall intestineen_US
dc.subjectpublic health and epidemiologyen_US
dc.subjectscreeningen_US
dc.titleEffective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphismsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorde Bakker, Paul I Wen
dc.date.available2011-11-09T16:56:37Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0002270*
dash.authorsorderedfalse
dash.contributor.affiliatedde Bakker, Paul


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