ArticleNucleic acids research2008
Effect of polymorphisms within probe-target sequences on olignonucleotide microarray experiments.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
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- Exon Array Biomarkers for the Differential Diagnosis of Schizophrenia and Bipolar Disorder.Molecular neuropsychiatry · 2018Article
- Reliable quantification of rhinovirus species C using real-time PCR.Journal of virological methods · 2016Article
- Genome-wide studies of von Willebrand factor propeptide identify loci contributing to variation in propeptide levels and von Willebrand factor clearance.Journal of thrombosis and haemostasis : JTH · 2016Article
- Variation in Drosophila melanogaster central metabolic genes appears driven by natural selection both within and between populations.Proceedings. Biological sciences · 2015Article
- Natural genetic variation impacts expression levels of coding, non-coding, and antisense transcripts in fission yeast.Molecular systems biology · 2014Article
- Allelic mapping bias in RNA-sequencing is not a major confounder in eQTL studies.Genome biology · 2014Article
- A small system--high-resolution study of metabolic adaptation in the central metabolic pathway to temperate climates in Drosophila melanogaster.Molecular biology and evolution · 2014Article
- Genetic dissection of the Drosophila melanogaster female head transcriptome reveals widespread allelic heterogeneity.PLoS genetics · 2014Article
- Comparative functional genomics and the bovine macrophage response to strains of the mycobacterium genus.Frontiers in immunology · 2014Review
- The use of haplotype-specific transcripts improves sample annotation consistency.Biomarker research · 2014Article
- Integrative genomics and transcriptomics analysis of human embryonic and induced pluripotent stem cells.BioData mining · 2014Article
- Article
- Systematic identification of trans eQTLs as putative drivers of known disease associations.Nature genetics · 2013Article
- GLiMMPS: robust statistical model for regulatory variation of alternative splicing using RNA-seq data.Genome biology · 2013Article
- Resolving the polymorphism-in-probe problem is critical for correct interpretation of expression QTL studies.Nucleic acids research · 2013Article
- Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array.Epigenetics & chromatin · 2013Article
- Modeling host genetic regulation of influenza pathogenesis in the collaborative cross.PLoS pathogens · 2013Article
Corrections and comments
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Hybridization-based technologies, such as microarrays, rely on precise probe-target interactions to ensure specific and accurate measurement of RNA expression. Polymorphisms present in the probe-target sequences have been shown to alter probe- hybridization affinities, leading to reduced signal intensity measurements and resulting in false-positive results. Here, we characterize this effect on exon and gene expression estimates derived from the Affymetrix Exon Array. We conducted an association analysis between expression levels of probes, exons and transcripts and the genotypes of neighboring SNPs in 57 CEU HapMap individuals. We quantified the dependence of the effect of genotype on signal intensity with respect to the number of polymorphisms within target sequences, number of affected probes and position of the polymorphism within each probe. The effect of SNPs is quite severe and leads to considerable false-positive rates, particularly when the analysis is performed at the exon level and aimed at detecting alternative splicing events. Finally, we propose simple solutions, based on 'masking' probes, which are putatively affected by polymorphisms and show that such strategy results in a large decrease in false-positive rates, with a very modest reduction in coverage of the transcriptome.
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