Apr 3, 2012

Identification of allele-specific alternative mRNA processing via transcriptome sequencing

Nucleic Acids Research
Gang LiXinshu Xiao

Abstract

Establishing the functional roles of genetic variants remains a significant challenge in the post-genomic era. Here, we present a method, allele-specific alternative mRNA processing (ASARP), to identify genetically influenced mRNA processing events using transcriptome sequencing (RNA-Seq) data. The method examines RNA-Seq data at both single-nucleotide and whole-gene/isoform levels to identify allele-specific expression (ASE) and existence of allele-specific regulation of mRNA processing. We applied the methods to data obtained from the human glioblastoma cell line U87MG and primary breast cancer tissues and found that 26-45% of all genes with sufficient read coverage demonstrated ASE, with significant overlap between the two cell types. Our methods predicted potential mechanisms underlying ASE due to regulations affecting either whole-gene-level expression or alternative mRNA processing, including alternative splicing, alternative polyadenylation and alternative transcriptional initiation. Allele-specific alternative splicing and alternative polyadenylation may explain ASE in hundreds of genes in each cell type. Reporter studies following these predictions identified the causal single nucleotide variants (SNVs) for several all...Continue Reading

Mentioned in this Paper

Genome-Wide Association Study
Genome
Sequence Determinations, RNA
Transcription, Genetic
Transcription Initiation
MRNA Processing
Regulation of mRNA Processing
Genomics
Sequencing
Nucleotides

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