Global patterns of cis variation in human cells revealed by high-density allelic expression analysis.
Cis-acting variants altering gene expression are a source of phenotypic differences. The cis-acting components of expression variation can be identified through the mapping of differences in allelic expression (AE), which is the measure of relative expression between two allelic transcripts. We generated a map of AE associated SNPs using quantitative measurements of AE on Illumina Human1M BeadChips. In 53 lymphoblastoid cell lines derived from donors of European descent, we identified common cis variants affecting 30% (2935/9751) of the measured RefSeq transcripts at 0.001 permutation significance. The pervasive influence of cis-regulatory variants, which explain 50% of population variation in AE, extend to full-length transcripts and their isoforms as well as to unannotated transcripts. These strong effects facilitate fine mapping of cis-regulatory SNPs, as demonstrated by dissection of heritable control of transcripts in the systemic lupus erythematosus-associated C8orf13-BLK region in chromosome 8. The dense collection of associations will facilitate large-scale isolation of cis-regulatory SNPs.
Ge
Bing
B
McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada.
Pokholok
Dmitry K
DK
Kwan
Tony
T
Grundberg
Elin
E
Morcos
Lisanne
L
Verlaan
Dominique J
DJ
Le
Jennie
J
Koka
Vonda
V
Lam
Kevin C L
KC
Gagné
Vincent
V
Dias
Joana
J
Hoberman
Rose
R
Montpetit
Alexandre
A
Joly
Marie-Michele
MM
Harvey
Edward J
EJ
Sinnett
Daniel
D
Beaulieu
Patrick
P
Hamon
Robert
R
Graziani
Alexandru
A
Dewar
Ken
K
Harmsen
Eef
E
Majewski
Jacek
J
Göring
Harald H H
HH
Naumova
Anna K
AK
Blanchette
Mathieu
M
Gunderson
Kevin L
KL
Pastinen
Tomi
T
D000483:Alleles; D002460:Cell Line; D020869:Gene Expression Profiling; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008214:Lymphocytes / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D014158:Transcription, Genetic