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


CONCLUSIONS
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.
Babak
Tomas
T
Rosetta Inpharmatics, LLC, 401 Terry Ave N, Seattle, WA 98109, USA.
Garrett-Engele
Philip
P
Armour
Christopher D
CD
Raymond
Christopher K
CK
Keller
Mark P
MP
Chen
Ronghua
R
Rohl
Carol A
CA
Johnson
Jason M
JM
Attie
Alan D
AD
Fraser
Hunter B
HB
Schadt
Eric E
EE
D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D014644:Genetic Variation; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D040641:Quantitative Trait Loci; D022661:RNA, Untranslated / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D014158:Transcription, Genetic
D016375:Antisense Elements (Genetics); D022661:RNA, Untranslated