Journal Article10.1126/SCIENCE.1098918
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.
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Abstract: The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.
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Citations
From microscopes to microarrays: dissecting recurrent chromosomal rearrangements
TL;DR: A group of genomic disorders that are mediated by segmental duplications are reviewed, emphasizing the impact that high-throughput detection methods and the availability of the human genome sequence have had on their dissection and diagnosis.
Genome-wide Copy Number Profiling on High-density Bacterial Artificial Chromosomes, Single-nucleotide Polymorphisms, and Oligonucleotide Microarrays: A Platform Comparison based on Statistical Power Analysis
Jayne Y. Hehir-Kwa,Michael Egmont-Petersen,Irene M. Janssen,Dominique Smeets,Ad Geurts van Kessel,Joris A. Veltman +5 more
TL;DR: A novel method to estimate the ability of a microarray to detect genomic copy-number variations of different sizes and types is presented, which found that the high-density oligonucleotide platforms are superior to the BAC platform for the genome-wide detection of copy- number variations smaller than 1 Mb.
Whole-genome microarray analysis in prenatal specimens identifies clinically significant chromosome alterations without increase in results of unclear significance compared to targeted microarray.
Justine Coppinger,Sarah Alliman,Allen N. Lamb,Beth S. Torchia,Bassem A. Bejjani,Lisa G. Shaffer +5 more
TL;DR: To determine the detection rates of whole‐genome microarray technology compared to targeted microarray analysis for chromosome abnormalities in prenatal samples submitted for diagnostic testing, a large number of samples from women with high‐risk pregnancies were examined.
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Microdeletions and microduplications in patients with congenital heart disease and multiple congenital anomalies.
Elizabeth Goldmuntz,Prasuna Paluru,Joseph T. Glessner,Hakon Hakonarson,Hakon Hakonarson,Jaclyn A. Biegel,Peter White,Peter White,Xiaowu Gai,Tamim H. Shaikh +9 more
TL;DR: Genome-wide analysis in patients with congenital heart disease and additional phenotypes has identified potentially pathogenic CNVs affecting genes involved in cardiac development, which warrant further evaluation in similarly syndromic and nonsyndromic cardiac cohorts.
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Human gene copy number spectra analysis in congenital heart malformations
Aoy Tomita-Mitchell,Donna K. Mahnke,Craig A. Struble,Maureen E. Tuffnell,Karl Stamm,Mats Hidestrand,Susan E. Harris,Mary Goetsch,Pippa Simpson,David P. Bick,Ulrich Broeckel,Andrew N. Pelech,James S. Tweddell,Michael E. Mitchell +13 more
TL;DR: The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge as mentioned in this paper. Although CNVs including genes can confer disease risk, relationships between...
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Cohen Syndrome Is Caused by Mutations in a Novel Gene, COH1, Encoding a Transmembrane Protein with a Presumed Role in Vesicle-Mediated Sorting and Intracellular Protein Transport
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