Copy number variation detection and genotyping from exome sequence data.

Genome Research
Niklas KrummEvan E Eichler

Abstract

While exome sequencing is readily amenable to single-nucleotide variant discovery, the sparse and nonuniform nature of the exome capture reaction has hindered exome-based detection and characterization of genic copy number variation. We developed a novel method using singular value decomposition (SVD) normalization to discover rare genic copy number variants (CNVs) as well as genotype copy number polymorphic (CNP) loci with high sensitivity and specificity from exome sequencing data. We estimate the precision of our algorithm using 122 trios (366 exomes) and show that this method can be used to reliably predict (94% overall precision) both de novo and inherited rare CNVs involving three or more consecutive exons. We demonstrate that exome-based genotyping of CNPs strongly correlates with whole-genome data (median r(2) = 0.91), especially for loci with fewer than eight copies, and can estimate the absolute copy number of multi-allelic genes with high accuracy (78% call level). The resulting user-friendly computational pipeline, CoNIFER (copy number inference from exome reads), can reliably be used to discover disruptive genic CNVs missed by standard approaches and should have broad application in human genetic studies of disease.

References

Jun 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jan O KorbelMark B Gerstein
May 3, 2008·Nature·Jeffrey M KiddEvan E Eichler
Jun 3, 2008·Nature Methods·Ali MortazaviBarbara Wold
May 19, 2009·Genome Research·Fereydoun HormozdiariS Cenk Sahinalp
Oct 9, 2009·Nature·Donald F ConradMatthew E Hurles
Nov 17, 2009·Nature Genetics·Sarah B NgMichael J Bamshad
Aug 3, 2010·Nature Methods·Faraz HachS Cenk Sahinalp
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Oct 30, 2010·Science·Peter H SudmantEvan E Eichler
Mar 15, 2011·American Journal of Human Genetics·Catarina D CampbellEvan E Eichler
Aug 11, 2011·Bioinformatics·Jarupon Fah SathirapongsasutiStanley F Nelson
Aug 23, 2011·Annual Review of Genetics·Santhosh GirirajanEvan E Eichler
Sep 29, 2011·Nature Reviews. Genetics·Michael J BamshadJay Shendure
Dec 20, 2011·Nature Methods·Emre KarakocEvan E Eichler

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Citations

Oct 5, 2012·The New England Journal of Medicine·Heather C Mefford
Feb 16, 2013·Bioinformatics·Sangwoo KimVineet Bafna
Feb 16, 2013·Circulation Research·UNKNOWN Pediatric Cardiac Genomics ConsortiumEllen Rosenberg
Feb 13, 2013·BMC Bioinformatics·Kaushalya C AmarasingheSaman K Halgamuge
Oct 22, 2013·BMC Genomics·Fayeza F KhanJohn A L Armour
Jan 4, 2013·PloS One·Rafael Valdés-MasXose S Puente
May 22, 2013·PloS One·Ana Isabel AntonRocio Gonzalez-Conejero
Apr 8, 2014·Genes·Megan J Puckelwartz, Elizabeth M McNally
Jan 18, 2014·Nature Reviews. Genetics·David SimsChris P Ponting
Apr 2, 2014·Nature Genetics·Jianxin ShiMaria Teresa Landi
Aug 12, 2014·Human Genetics·Edward J Hollox, Boon-Peng Hoh
Apr 30, 2014·Annual Review of Genomics and Human Genetics·Corey T WatsonHeather C Mefford
Jul 26, 2014·Genetic Testing and Molecular Biomarkers·Guney BademciMustafa Tekin
Aug 28, 2014·Bioinformatics·Evangelos Bellos, Lachlan J M Coin
Aug 30, 2014·BMC Genomics·Kaushalya C AmarasingheSaman K Halgamuge
Sep 18, 2014·Nucleic Acids Research·Evangelos BellosSonia Davila
Oct 18, 2014·BMC Bioinformatics·Yan GuoYu Shyr
May 2, 2014·Nucleic Acids Research·Erik S HopmansHanlee P Ji
Feb 19, 2013·Circulation. Cardiovascular Genetics·Nadine NortonUNKNOWN National Heart, Lung, and Blood Institute GO Exome Sequencing Project and the Exome Sequencing Project Family Studies Projec
Jan 12, 2016·The Journal of Clinical Investigation·Yavuz BayramJames R Lupski
Dec 29, 2015·American Journal of Human Genetics·Kitty K LoLyn S Chitty

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