Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation

BMC Genomics. 2010 Aug 13:11:473. doi: 10.1186/1471-2164-11-473.

Abstract

Background: Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application.

Results: Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants.

Conclusion: Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.

MeSH terms

  • Alleles
  • Alternative Splicing
  • Animals
  • Antisense Elements (Genetics) / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression*
  • Genetic Variation*
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Quantitative Trait Loci*
  • RNA, Untranslated / genetics
  • Sequence Analysis, DNA / methods*
  • Transcription, Genetic

Substances

  • Antisense Elements (Genetics)
  • RNA, Untranslated