Impact of whole genome amplification on analysis of copy number variants. Export

@article{citeulike:3063776, abstract = {Large-scale copy number variants (CNVs) have recently been recognized to play a role in human genome variation and disease. Approaches for analysis of CNVs in small samples such as microdissected tissues can be confounded by limited amounts of material. To facilitate analyses of such samples, whole genome amplification (WGA) techniques were developed. In this study, we explored the impact of Phi29 multiple-strand displacement amplification on detection of CNVs using oligonucleotide arrays. We extracted DNA from fresh frozen lymph node samples and used this for amplification and analysis on the Affymetrix Mapping 500k SNP array platform. We demonstrated that the WGA procedure introduces hundreds of potentially confounding CNV artifacts that can obscure detection of bona fide variants. Our analysis indicates that many artifacts are reproducible, and may correlate with proximity to chromosome ends and GC content. Pair-wise comparison of amplified products considerably reduced the number of apparent artifacts and partially restored the ability to detect real CNVs. Our results suggest WGA material may be appropriate for copy number analysis when amplified samples are compared to similarly amplified samples and that only the CNVs with the greatest significance values detected by such comparisons are likely to be representative of the unamplified samples.}, address = {Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.}, author = {Pugh, T. J. and Delaney, A. D. and Farnoud, N. and Flibotte, S. and Griffith, M. and Li, H. I. and Qian, H. and Farinha, P. and Gascoyne, R. D. and Marra, M. A.}, citeulike-article-id = {3063776}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/18559357}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=18559357}, issn = {1362-4962}, journal = {Nucleic acids research}, keywords = {amplification, copy, genome, number}, month = {August}, number = {13}, posted-at = {2008-07-30 17:48:52}, priority = {2}, title = {Impact of whole genome amplification on analysis of copy number variants.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18559357}, volume = {36}, year = {2008} }

TY - JOUR ID - citeulike:3063776 L3 - citeulike-article-id:3063776 N2 - Large-scale copy number variants (CNVs) have recently been recognized to play a role in human genome variation and disease. Approaches for analysis of CNVs in small samples such as microdissected tissues can be confounded by limited amounts of material. To facilitate analyses of such samples, whole genome amplification (WGA) techniques were developed. In this study, we explored the impact of Phi29 multiple-strand displacement amplification on detection of CNVs using oligonucleotide arrays. We extracted DNA from fresh frozen lymph node samples and used this for amplification and analysis on the Affymetrix Mapping 500k SNP array platform. We demonstrated that the WGA procedure introduces hundreds of potentially confounding CNV artifacts that can obscure detection of bona fide variants. Our analysis indicates that many artifacts are reproducible, and may correlate with proximity to chromosome ends and GC content. Pair-wise comparison of amplified products considerably reduced the number of apparent artifacts and partially restored the ability to detect real CNVs. Our results suggest WGA material may be appropriate for copy number analysis when amplified samples are compared to similarly amplified samples and that only the CNVs with the greatest significance values detected by such comparisons are likely to be representative of the unamplified samples. IS - 13 JF - Nucleic acids research SN - 1362-4962 AD - Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada. TI - Impact of whole genome amplification on analysis of copy number variants. VL - 36 KW - amplification KW - copy KW - genome KW - number AU - Pugh, TJ AU - Delaney, AD AU - Farnoud, N AU - Flibotte, S AU - Griffith, M AU - Li, HI AU - Qian, H AU - Farinha, P AU - Gascoyne, RD AU - Marra, MA PY - 2008/08// UR - http://view.ncbi.nlm.nih.gov/pubmed/18559357 ER -