Relative impact of nucleotide and copy number variation on gene expression phenotypes.
Extensive studies are currently being performed to associate disease susceptibility with one form of genetic variation, namely, single-nucleotide polymorphisms (SNPs). In recent years, another type of common genetic variation has been characterized, namely, structural variation, including copy number variants (CNVs). To determine the overall contribution of CNVs to complex phenotypes, we have performed association analyses of expression levels of 14,925 transcripts with SNPs and CNVs in individuals who are part of the International HapMap project. SNPs and CNVs captured 83.6% and 17.7% of the total detected genetic variation in gene expression, respectively, but the signals from the two types of variation had little overlap. Interrogation of the genome for both types of variants may be an effective way to elucidate the causes of complex phenotypes and disease in humans.
Stranger
Barbara E
BE
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Forrest
Matthew S
MS
Dunning
Mark
M
Ingle
Catherine E
CE
Beazley
Claude
C
Thorne
Natalie
N
Redon
Richard
R
Bird
Christine P
CP
de Grassi
Anna
A
Lee
Charles
C
Tyler-Smith
Chris
C
Carter
Nigel
N
Scherer
Stephen W
SW
Tavaré
Simon
S
Deloukas
Panagiotis
P
Hurles
Matthew E
ME
Dermitzakis
Emmanouil T
ET
D002460:Cell Line; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis