Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes
Barbara E. Stranger,1
Matthew S. Forrest,1
Mark Dunning,2
Catherine E. Ingle,1
Claude Beazley,1
Natalie Thorne,2
Richard Redon,1
Christine P. Bird,1
Anna de Grassi,3
Charles Lee,4,5
Chris Tyler-Smith,1
Nigel Carter,1
Stephen W. Scherer,6,7
Simon Tavaré,2,8
Panagiotis Deloukas,1
Matthew E. Hurles,1*
Emmanouil T. Dermitzakis1*
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.
1 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
2 Department of Oncology, University of Cambridge, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
3 Istituto di Tecnologie Biomediche-Sezione di Bari, Consiglio Nazionale della Ricerche (CNR), 70126 Bari, Italy.
4 Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
5 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
6 The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, MaRS Centre, Toronto, Ontario, M5G 1L7, Canada.
7 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada.
8 Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089–2910, USA.
* To whom correspondence should be addressed. E-mail: md4{at}sanger.ac.uk (E.T.D.); meh{at}sanger.ac.uk (M.E.H.)
