[ged] paper for next week journal club

[preeyano at msu.edu]

Hi, guys

I'm presenting this paper next week, Monday 2pm.
http://nar.oxfordjournals.org/content/early/2012/03/28/nar.gks280.full

Identification of allele-specific alternative mRNA processing via  
transcriptome sequencing.

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 allele-specific  
alternative splicing events. Finally, many genes identified in our  
study were also reported as disease/phenotype-associated genes in  
genome-wide association studies. Future applications of our approach  
may provide ample insights for a better understanding of the genetic  
basis of gene regulation underlying phenotypic diversity and disease  
mechanisms.