RT Journal
A1 Verlaan, Dominique J.
A1 Ge, Bing
A1 Grundberg, Elin
A1 Hoberman, Rose
A1 Lam, Kevin C.L.
A1 Koka, Vonda
A1 Dias, Joana
A1 Gurd, Scott
A1 Martin, Nicolas W.
A1 Mallmin, Hans
A1 Nilsson, Olof
A1 Harmsen, Eef
A1 Dewar, Ken
A1 Kwan, Tony
A1 Pastinen, Tomi
T1 Targeted screening of cis-regulatory variation in human haplotypes
JF Genome Research 
JO Genome Research 
YR 2009 
FD January 01 
VO 19 
IS 1 
SP 118 
OP 127 
DO 10.1101/gr.084798.108 
UL http://genome.cshlp.org/content/19/1/118.abstract 
AB Regulatory cis-acting variants account for a large proportion of gene expression variability in populations. Cis-acting differences can be specifically measured by comparing relative levels of allelic transcripts within a sample. Allelic expression (AE) mapping for cis-regulatory variant discovery has been hindered by the requirements of having informative or heterozygous single nucleotide polymorphisms (SNPs) within genes in order to assign the allelic origin of each transcript. In this study we have developed an approach to systematically screen for heritable cis-variants in common human haplotypes across >1000 genes. In order to achieve the highest level of information per haplotype studied, we carried out allelic expression measurements by using both intronic and exonic SNPs in primary transcripts. We used a novel RNA pooling strategy in immortalized lymphoblastoid cell lines (LCLs) and primary human osteoblast cell lines (HObs) to allow for high-throughput AE. Screening hits from RNA pools were further validated by performing allelic expression mapping in individual samples. Our results indicate that >10% of expressed genes in human LCLs show genotype-linked AE. In addition, we have validated cis-acting variants in over 20 genes linked with common disease susceptibility in recent genome-wide studies. More generally, our results indicate that RNA pooling coupled with AE read-out by second generation sequencing or by other methods provides a high-throughput tool for cataloging the impact of common noncoding variants in the human genome.