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.
McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada.
Bing
B
Ge
Dmitry K
DK
Pokholok
Tony
T
Kwan
Elin
E
Grundberg
Lisanne
L
Morcos
Dominique J
DJ
Verlaan
Jennie
J
Le
Vonda
V
Koka
Kevin C L
KC
Lam
Vincent
V
Gagné
Joana
J
Dias
Rose
R
Hoberman
Alexandre
A
Montpetit
Marie-Michele
MM
Joly
Edward J
EJ
Harvey
Daniel
D
Sinnett
Patrick
P
Beaulieu
Robert
R
Hamon
Alexandru
A
Graziani
Ken
K
Dewar
Eef
E
Harmsen
Jacek
J
Majewski
Harald H H
HH
Göring
Anna K
AK
Naumova
Mathieu
M
Blanchette
Kevin L
KL
Gunderson
Tomi
T
Pastinen
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