Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes
Authors: Stranger, Barbara E. and Forrest, Matthew S. and Dunning, Mark and Ingle, Catherine E. and Beazley, Claude and Thorne, Natalie and Redon, Richard and Bird, Christine P. and de Grassi, Anna and Lee, Charles and Tyler-Smith, Chris and Carter, Nigel and Scherer, Stephen W. and Tavaré, Simon and Deloukas, Panagiotis and Hurles, Matthew E. and Dermitzakis, Emmanouil T. Year: 2007 Journal: Science
Abstract
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.
Notes
Extracted Concepts
- Copy number variations account for substantial but secondary gene expression variation
- Interrogating both SNPs and CNVs is necessary for understanding complex phenotypes
- SNP and CNV signals show minimal overlap in gene expression associations
- SNPs capture majority of genetic variation affecting gene expression