Methods and strategies for analyzing copy number variation using DNA microarrays.
Reads0
Chats0
TLDR
Current challenges involve developing methods not only for detecting and cataloging CNVs in human populations at increasingly higher resolution but also for determining the association of CNVs with biological function, recent human evolution, and common and complex human disease.Abstract:
The association of DNA copy-number variation (CNV) with specific gene function and human disease has been long known, but the wide scope and prevalence of this form of variation has only recently been fully appreciated. The latest studies using microarray technology have demonstrated that as much as 12% of the human genome and thousands of genes are variable in copy number, and this diversity is likely to be responsible for a significant proportion of normal phenotypic variation. Current challenges involve developing methods not only for detecting and cataloging CNVs in human populations at increasingly higher resolution but also for determining the association of CNVs with biological function, recent human evolution, and common and complex human disease.read more
Citations
More filters
Journal ArticleDOI
Coming of age: ten years of next-generation sequencing technologies
TL;DR: These and other strategies are providing researchers and clinicians a variety of tools to probe genomes in greater depth, leading to an enhanced understanding of how genome sequence variants underlie phenotype and disease.
Journal ArticleDOI
High-Throughput Droplet Digital PCR System for Absolute Quantitation of DNA Copy Number
Benjamin J. Hindson,Kevin D. Ness,Donald A. Masquelier,Phillip Belgrader,Nicholas J. Heredia,Anthony J. Makarewicz,Isaac J. Bright,Michael Y. Lucero,Amy L. Hiddessen,Tina C. Legler,Tyler K. Kitano,Michael R. Hodel,Jonathan Petersen,Paul Wyatt,Erin R. Steenblock,Pallavi Shah,Luc J. Bousse,Camille B. Troup,Jeffrey Clark Mellen,Dean K. Wittmann,Nicholas G. Erndt,Thomas H. Cauley,Ryan T. Koehler,Austin P. So,Simant Dube,Klint Rose,Luz Montesclaros,Shenglong Wang,David P. Stumbo,Shawn Hodges,Steven Romine,Fred P. Milanovich,Helen E. White,John F. Regan,George Karlin-Neumann,Christopher Hindson,Serge Saxonov,Bill W. Colston +37 more
TL;DR: A high-throughput droplet digital PCR system that enables processing of ∼2 million PCR reactions using conventional TaqMan assays with a 96-well plate workflow is described that will allow researchers to explore complex genetic landscapes, discover and validate new disease associations, and define a new era of molecular diagnostics.
Journal ArticleDOI
PennCNV: An integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data
Kai Wang,Mingyao Li,Dexter Hadley,Rui Liu,Joseph T. Glessner,Struan F.A. Grant,Hakon Hakonarson,Maja Bucan +7 more
TL;DR: PennCNV, a hidden Markov model (HMM) based approach, is presented for kilobase-resolution detection of CNVs from Illumina high-density SNP genotyping data, demonstrating the feasibility of whole-genome fine-mapping ofCNVs via high- density SNP genotypesing.
Journal ArticleDOI
CNVnator: An approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing
TL;DR: By genotyping CNVs in the CEPH, Yoruba, and Chinese-Japanese populations, it is estimated that at least 11% of all CNV loci involve complex, multi-allelic events, a considerably higher estimate than reported earlier.
Journal ArticleDOI
Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly
Ernest T. Lam,Alex Hastie,Chin Lin,Dean Ehrlich,Somes K. Das,Michael D. Austin,Paru Deshpande,Han Cao,Niranjan Nagarajan,Ming Xiao,Pui-Yan Kwok +10 more
TL;DR: This work demonstrates the analysis, individually and as mixtures, of 95 bacterial artificial chromosome clones that cover the 4.7-Mb human major histocompatibility complex region and obtains accurate, haplotype-resolved, sequence motif maps hundreds of kilobases in length.
References
More filters
Journal ArticleDOI
A haplotype map of the human genome
John W. Belmont,Andrew Boudreau,Suzanne M. Leal,Paul Hardenbol,Shiran Pasternak,David A. Wheeler,Thomas D. Willis,Fuli Yu,Huanming Yang,Gao Yang,H. B. Hu,Weitao Hu,Chaohua Li,Wei Lin,Siqi Liu,Hao Pan,Xiaoli Tang,Jian Wang,Wei Wang,Jun Yu,Bo Zhang,Qingrun Zhang,Hongbin Zhao,Jun Zhou,Rachel Barry,Brendan Blumenstiel,Amy L. Camargo,Matthew Defelice,Maura Faggart,Mary Goyette,Supriya Gupta,Jamie Moore,Huy Nguyen,Melissa Parkin,Jessica Roy,Erich Stahl,Ellen Winchester,David Altshuler,Yan Shen,Zhijian Yao,Wei Huang,Xun Chu,Yungang He,Li Jin,Yangfan Liu,Yayun Shen,Weiwei Sun,Haifeng Wang,Yi Wang,Ying Wang,Xiaoyan Xiong,Liang Xu,Mary M.Y. Waye,Stephen Kwok-Wing Tsui,Hong Xue,J. Tze Fei Wong,Launa M. Galver,Jian-Bing Fan,Sarah S. Murray,Arnold Oliphant,Mark S. Chee,Alexandre Montpetit,Fanny Chagnon,Vincent Ferretti,Martin Leboeuf,Jean François Olivier,Michael S. Phillips,Stéphanie Roumy,Clémentine Sallée,Andrei Verner,Thomas J. Hudson,Kelly A. Frazer,Dennis G. Ballinger,David R. Cox,David A. Hinds,Laura L. Stuve,Pui-Yan Kwok,Dongmei Cai,Daniel C. Koboldt,Raymond D. Miller,Ludmila Pawlikowska,Patricia Taillon-Miller,Ming Xiao,Lap-Chee Tsui,William Mak,Pak C. Sham,You-Qiang Song,Paul K.H. Tam,Yusuke Nakamura,Takahisa Kawaguchi,Takuya Kitamoto,Takashi Morizono,Atsushi Nagashima,Yozo Ohnishi,Akihiro Sekine,Toshihiro Tanaka,Panos Deloukas,Christine P. Bird,Marcos Delgado,Emmanouil T. Dermitzakis,Rhian Gwilliam,Sarah E. Hunt,Jonathan Morrison,Don Powell,Barbara E. Stranger,Pamela Whittaker,David R. Bentley,Paul I.W. de Bakker,Jeffrey C. Barrett,Ben Fry,Julian Maller,Steve McCarroll,Nick Patterson,Itsik Pe'er,Shaun Purcell,Daniel J. Richter,Pardis C. Sabeti,Richa Saxena,Stephen F. Schaffner,Patrick Varilly,Lincoln Stein,Lalitha Krishnan,Albert V. Smith,Gudmundur A. Thorisson,Aravinda Chakravarti,Peter E. Chen,David J. Cutler,Carl S. Kashuk,Shin Lin,Gonçalo R. Abecasis,Weihua Guan,Heather M. Munro,Zhaohui S. Qin,Daryl J. Thomas,Gilean McVean,Leonardo Bottolo,Susana Eyheramendy,Colin Freeman,Jonathan Marchini,Simon Myers,Chris C. A. Spencer,Matthew Stephens,Peter Donnelly,Lon R. Cardon,Geraldine M. Clarke,David M. Evans,Andrew P. Morris,Bruce S. Weir,Tatsuhiko Tsunoda,James C. Mullikin,Stephen T. Sherry,Michael Feolo,Houcan Zhang,Changqing Zeng,Hui Zhao,Ichiro Matsuda,Yoshimitsu Fukushima,Darryl Macer,Eiko Suda,Charles N. Rotimi,Clement Adebamowo,Ike Ajayi,Toyin Aniagwu,Patricia A. Marshall,Chibuzor Nkwodimmah,Charmaine D.M. Royal,Mark Leppert,Missy Dixon,Andy Peiffer,Renzong Qiu,Alastair Kent,Kazuto Kato,Norio Niikawa,Isaac F. Adewole,Bartha Maria Knoppers,Morris W. Foster,Ellen Wright Clayton,Jessica Watkin,Richard A. Gibbs,Donna M. Muzny,Lynne V. Nazareth,Erica Sodergren,George M. Weinstock,Imtiaz Yakub,Stacey Gabriel,Robert C. Onofrio,Liuda Ziaugra,Bruce W. Birren,Mark J. Daly,Richard K. Wilson,Lucinda Fulton,Jane Rogers,John Burton,Nigel P. Carter,C M Clee,Mark Griffiths,Matthew C. Jones,Kirsten McLay,Robert W. Plumb,Mark T. Ross,Sarah Sims,David Willey,Zhu Chen,Hua Han,L. Kang,Martin Godbout,John C. Wallenburg,Paul L'Archevêque,Guy Bellemare,Koji Saeki,Hongguang Wang,Daochang An,Hongbo Fu,Qing Li,Zhen Wang,Renwu Wang,Arthur L. Holden,Lisa D. Brooks,Jean E. McEwen,Christianne R. Bird,Mark S. Guyer,Patrick J. Nailer,Vivian Ota Wang,Jane Peterson,Michael Shi,Jack Spiegel,Lawrence M. Sung,Jonathan Witonsky,Lynn F. Zacharia,Francis S. Collins,Karen Kennedy,Ruth Jamieson,John Stewart +232 more
TL;DR: A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted.
Journal ArticleDOI
Global variation in copy number in the human genome
Richard Redon,Shumpei Ishikawa,Karen R. Fitch,Lars Feuk,George H. Perry,T. Daniel Andrews,Heike Fiegler,Michael H. Shapero,Andrew R. Carson,Wenwei Chen,Eun Kyung Cho,Stephanie Dallaire,Jennifer L. Freeman,Juan R. González,Mònica Gratacòs,Jing Huang,Dimitrios Kalaitzopoulos,Daisuke Komura,Jeffrey R. MacDonald,Christian R. Marshall,Rui Mei,Lyndal Montgomery,Keunihiro Nishimura,Kohji Okamura,Fan Shen,Martin J. Somerville,Joelle Tchinda,Armand Valsesia,Cara Woodwark,Fengtang Yang,Junjun Zhang,Tatiana Zerjal,Jane Zhang,Lluís Armengol,Donald F. Conrad,Xavier Estivill,Chris Tyler-Smith,Nigel P. Carter,Hiroyuki Aburatani,Charles Lee,Keith W. Jones,Stephen W. Scherer,Matthew E. Hurles +42 more
TL;DR: A first-generation CNV map of the human genome is constructed through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia, underscoring the importance of CNV in genetic diversity and evolution and the utility of this resource for genetic disease studies.
Journal ArticleDOI
Detection of large-scale variation in the human genome.
A. John Iafrate,Lars Feuk,Miguel Rivera,Miguel Rivera,Marc L. Listewnik,Patricia K. Donahoe,Ying Qi,Stephen W. Scherer,Charles Lee,Charles Lee +9 more
TL;DR: This article identified 255 loci across the human genome that contain genomic imbalances among unrelated individuals, and revealed that half of these regions overlap with genes, and many coincide with segmental duplications or gaps in human genome assembly.
Journal ArticleDOI
Large-Scale Copy Number Polymorphism in the Human Genome
Jonathan Sebat,B. Lakshmi,Jennifer Troge,Joan Alexander,Janet M. Young,Pär Lundin,Susanne Månér,Hillary Massa,Megan Walker,Maoyen Chi,Nicholas Navin,Robert Lucito,John Healy,James W. Hicks,Kenny Q. Ye,Andrew Reiner,T. Conrad Gilliam,Barbara J. Trask,Nick Patterson,Anders Zetterberg,Michael Wigler +20 more
TL;DR: It is shown that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans.
Journal ArticleDOI
Large-Scale Identification, Mapping, and Genotyping of Single-Nucleotide Polymorphisms in the Human Genome
David G. Wang,Jian-Bing Fan,Jian-Bing Fan,Chia-Jen Siao,Chia-Jen Siao,Anthony Berno,Anthony Berno,Peter M. Young,Peter M. Young,Ron Sapolsky,Ron Sapolsky,Ghassan Ghandour,Ghassan Ghandour,Nancy Perkins,Nancy Perkins,Ellen Winchester,Ellen Winchester,Jessica B. Spencer,Jessica B. Spencer,Leonid Kruglyak,Leonid Kruglyak,Lincoln Stein,Lincoln Stein,Linda Hsie,Linda Hsie,Thodoros Topaloglou,Thodoros Topaloglou,Earl Hubbell,Earl Hubbell,Elizabeth M. Robinson,Elizabeth M. Robinson,Michael P. Mittmann,Michael P. Mittmann,Macdonald S. Morris,Macdonald S. Morris,Naiping Shen,Naiping Shen,Dan Kilburn,Dan Kilburn,John D. Rioux,John D. Rioux,Chad Nusbaum,Chad Nusbaum,Steve Rozen,Steve Rozen,Thomas J. Hudson,Thomas J. Hudson,Robert J. Lipshutz,Robert J. Lipshutz,Mark S. Chee,Mark S. Chee,Eric S. Lander,Eric S. Lander +52 more
TL;DR: A large-scale survey for SNPs was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips, and a genetic map was constructed showing the location of 2227 candidate SNPs.
Related Papers (5)
Global variation in copy number in the human genome
Richard Redon,Shumpei Ishikawa,Karen R. Fitch,Lars Feuk,George H. Perry,T. Daniel Andrews,Heike Fiegler,Michael H. Shapero,Andrew R. Carson,Wenwei Chen,Eun Kyung Cho,Stephanie Dallaire,Jennifer L. Freeman,Juan R. González,Mònica Gratacòs,Jing Huang,Dimitrios Kalaitzopoulos,Daisuke Komura,Jeffrey R. MacDonald,Christian R. Marshall,Rui Mei,Lyndal Montgomery,Keunihiro Nishimura,Kohji Okamura,Fan Shen,Martin J. Somerville,Joelle Tchinda,Armand Valsesia,Cara Woodwark,Fengtang Yang,Junjun Zhang,Tatiana Zerjal,Jane Zhang,Lluís Armengol,Donald F. Conrad,Xavier Estivill,Chris Tyler-Smith,Nigel P. Carter,Hiroyuki Aburatani,Charles Lee,Keith W. Jones,Stephen W. Scherer,Matthew E. Hurles +42 more
Large-Scale Copy Number Polymorphism in the Human Genome
Jonathan Sebat,B. Lakshmi,Jennifer Troge,Joan Alexander,Janet M. Young,Pär Lundin,Susanne Månér,Hillary Massa,Megan Walker,Maoyen Chi,Nicholas Navin,Robert Lucito,John Healy,James W. Hicks,Kenny Q. Ye,Andrew Reiner,T. Conrad Gilliam,Barbara J. Trask,Nick Patterson,Anders Zetterberg,Michael Wigler +20 more
Strong Association of De Novo Copy Number Mutations with Autism
Jonathan Sebat,B. Lakshmi,Dheeraj Malhotra,Jennifer Troge,Christa Lese-Martin,Tom Walsh,Boris Yamrom,Seungtai Yoon,Alexander Krasnitz,Jude Kendall,Anthony Leotta,Deepa Pai,Ray Zhang,Yoon-ha Lee,James W. Hicks,Sarah J. Spence,Annette Lee,Kaija Puura,Terho Lehtimäki,David H. Ledbetter,Peter K. Gregersen,Joel D. Bregman,James S. Sutcliffe,Vaidehi Jobanputra,Wendy K. Chung,Dorothy Warburton,Mary Claire King,David Skuse,Daniel H. Geschwind,T. Conrad Gilliam,Kenny Ye,Michael Wigler +31 more