CNV  =  Copy Number Variants = Copy Number Variation
The gene copy number (also "copy number variants" or CNVs) is the number of copies of a particular gene in the genotype of an individual. Recent evidence shows that the gene copy number can be elevated in cancer cells.

The human genome is comprised of 6 billion chemical bases (or nucleotides) of DNA packaged into two sets of 23 chromosomes, one set inherited from each parent. The DNA encodes roughly 27,000 genes. It was generally thought that genes were almost always present in two copies in a genome. However, recent discoveries have revealed that large segments of DNA, ranging in size from thousands to millions of DNA bases, can vary in copy-number. Such copy number variations (or CNVs) can encompass genes leading to dosage imbalances. For example, genes that were thought to always occur in two copies per genome have now been found to sometimes be present in one, three, or more than three copies. In a few rare instances the genes are missing altogether (see figure).

Why are CNVs important?
Differences in the DNA sequence of our genomes contribute to our uniqueness. These changes influence most traits including susceptibility to disease. It was thought that single nucleotide changes (called SNPs) in DNA were the most prevalent and important form of genetic variation. The current studies reveal that CNVs comprise at least three times the total nucleotide content of SNPs. Since CNVs often encompass genes, they may have important roles both in human disease and drug response. Understanding the mechanisms of CNV formation may also help us better understand human genome evolution.

How does the new CNV map help?
The new global CNV map will transform medical research in four areas. The first and most important area is in hunting for genes underlying common diseases. To date, attempts to identify these genes have not really considered the role CNVs may play in human health. Second, the CNV map is being used to study familial genetic conditions. Third, there are thousands of severe developmental defects caused by chromosomal rearrangements. The CNV map is being used to exclude variation found in unaffected individuals, helping researchers to target the region that might be involved. The data generated will also contribute to a more accurate and complete human genome reference sequence used by all biomedical scientists.

FAQ about CNV

A curated catalogue of structural variation in the human genome

Center for Human and Clinical Genetics
Leiden University Medical Center

Genetic variation databases

The Copy Number Variation (CNV) Project

Genetic diseases are caused by a variety of different possible alterations (mutations) in DNA sequences. We are investigating gains and losses of large chunks of DNA sequence consisting of between ten thousand and five million letters (known as Copy Number Variation). This type of mutation has often been overlooked in previous surveys of mutations that cause genetic diseases. We do not know what proportion of genetic disease is caused by copy number variation (CNV), but we suspect that it is appreciable. We already know that many genetic diseases that occur in families result from these kinds of mutation, we also know that there are Copy Number Variants that protect against HIV infection and malaria. The contribution of CNV to the common, complex diseases (e.g. diabetes, heart disease) is presently unknown.
  • How much copy number variation (CNV) exists between human genomes?
  • How best can CNVs be incorporated into whole genome association studies?
  • What is the contribution of copy number variation to genetic disease?
  • What is the relative contribution of different mutational mechanisms to CNV?
  • What is the genomic impact of CNV on gene expression?
  • What role has copy number variation played in recent human evolution?


DatabasE of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources
The DECIPHER database of submicroscopic chromosomal imbalance collects clinical information about chromosomal microdeletions/duplications/insertions, translocations and inversions and displays this information on the human genome map with the aims of:
  • Increasing medical and scientific knowledge about chromosomal microdeletions/duplications
  • Improving medical care and genetic advice for individuals/families with submicroscopic chromosomal imbalance
  • Facilitating research into the study of genes which affect human development and health

New  papers:

Finding copy-number variants.
Nicol Rusk
Nature Methods 2008 5(11) 917

Large-scale copy number variants (CNVs): Distribution in normal subjects and FISH/real-time qPCR analysis.
Ying Qiao, Xudong Liu, Chansonette Harvard, Sarah L Nolin, W Ted Brown, Maryam Koochek, Jeanette JA Holden, ME Suzanne Lewis, and Evica Rajcan-Separovic
BMC Genomics 2007, 8: 167-177

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 Chen4, Eun Kyung Cho, Stephanie Dallaire, Jennifer L. Freeman, Juan R. Gonzalez, Monica Gratacos, Jing Huang, Dimitrios Kalaitzopoulos, Daisuke Komura, Jeffrey R. MacDonald, Christian R. Marshall, Rui Mei, Lyndal Montgomery, Kunihiro Nishimura, Kohji Okamura, Fan Shen, Martin J. Somerville, Joelle Tchinda, Armand Valsesia, Cara Woodwark, Fengtang Yang, Junjun Zhang, Tatiana Zerjal, Jane Zhang, Lluis 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
Nature (2006) Vol 444. 444-454

Accurate and objective copy number profiling using real-time quantitative PCR
Barbara D’haene, Jo Vandesompele, Jan Hellemans
Methods Vol 50, Issue 4, Pages 262-270

Taking qPCR to a higher level: Analysis of CNV reveals the power of high throughput qPCR to enhance quantitative resolution
Suzanne Weaver, Simant Dube, Alain Mir, Jian Qin, Gang Sun, Ramesh Ramakrishnan, Robert C. Jones, Kenneth J. Livak
Methods Vol 50, Issue 4,
Pages 271-276

Copy number variation and evolution in humans and chimpanzees.
Perry GH, Yang F, Marques-Bonet T, Murphy C, Fitzgerald T, Lee AS, Hyland C, Stone AC, Hurles ME, Tyler-Smith C, Eichler EE, Carter NP, Lee C, Redon R.
Genome Res. 2008 18(11): 1698-1710

Methods to detect and analyze copynumber variations at the genome-wideand locus-specific levels.
J.H. Lee and J.T. Jeon
Cytogenet Genome Res 123:333–342 (2008)

Methods and strategies for analyzing copy number variation using DNA microarrays.
Carter NP.
Nat Genet. 2007 39(7 Suppl): S16-21. Review.

Simultaneous mutation and copy number variation (CNV) detection by multiplex PCR-based GS-FLX sequencing.
Goossens D, Moens LN, Nelis E, Lenaerts AS, Glassee W, Kalbe A, Frey B, Kopal G, De Jonghe P, De Rijk P, Del-Favero J.
Hum Mutat. 2009 30(3): 472-476

Genome-wide analysis of transcript isoform variation in humans.
Kwan T, Benovoy D, Dias C, Gurd S, Provencher C, Beaulieu P, Hudson TJ, Sladek R, Majewski J.
Nat Genet. 2008 40(2): 225-231.

Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray.
Mark G Carter, Alexei A Sharov, Vincent VanBuren, Dawood B Dudekula, Condie E Carmack, Charlie Nelson and Minoru S H Ko
Genome Biology 2005, 6:R61

Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis.
Yang TL, Chen XD, Guo Y, Lei SF, Wang JT, Zhou Q, Pan F, Chen Y, Zhang ZX, Dong SS, Xu XH, Yan H, Liu X, Qiu C, Zhu XZ, Chen T, Li M, Zhang H, Zhang L, Drees BM, Hamilton JJ, Papasian CJ, Recker RR, Song XP, Cheng J, Deng HW.
Am J Hum Genet. 2008 83(6): 663-674

Comparative study of three PCR-based copy number variant approaches, CFMSA, M-PCR, and MLPA, in 22q11.2 deletion syndrome.
Yang C, Zhu X, Yi L, Shi Z, Wang H, Hu Y, Wang Y.
Genet Test Mol Biomarkers. 2009 13(6): 803-808

Copy-number variation genotyping of GSTT1 and GSTM1 gene deletions by real-time PCR.
Rose-Zerilli MJ, Barton SJ, Henderson AJ, Shaheen SO, Holloway JW.
Clin Chem. 2009 55(9): 1680-1685

High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals.
Nørskov MS, Frikke-Schmidt R, Loft S, Tybjaerg-Hansen A.
Clin Biochem. 2009 42(3): 201-209

Candidate gene copy number analysis by PCR and multicapillary electrophoresis.
Szantai E, Elek Z, Guttman A, Sasvari-Szekely M.
Electrophoresis. 2009 30(7): 1098-1101.

Statistical tools for transgene copy number estimation based on real-time PCR.
Joshua S Yuan, Jason Burris, Nathan R Stewart, Ayalew Mentewab and C Neal Stewart
BMC Bioinformatics 2007, 8(): S6

Copy number variation goes clinical.
A meeting report
Le Caignec C, Redon R.
Genome Biol. 2009;10(1): 301-303

Recent Papers:

The Patterns of Natural Variation in Human Genes.
Dana C. Crawford, Dayna T. Akey, and Deborah A. Nickerson
Annu. Rev. Genomics Hum. Genet. (2005) 6: 287–312

Structural variants: changing the landscape of chromosomes and design of disease studies.
Lars Feuk, Christian R. Marshall, Richard F. Wintle and Stephen W. Scherer
Human Molecular Genetics (2006) Vol. 15, Review Issue 1 R57–R66

Copy number variation: New insights in genome diversity.
Jennifer L. Freeman, George H. Perry, Lars Feuk, Richard Redon, Steven A. McCarroll, David M. Altshuler, Hiroyuki Aburatani, Keith W. Jones, Chris Tyler-Smith, Matthew E. Hurles, Nigel P. Carter, Stephen W. Scherer, and Charles Lee
Genome Research (2006) 16:949–961

Real-Time Quantitative PCR as an Alternative to Southern Blot or Fluorescence In Situ Hybridization for Detection of Gene Copy Number Changes.
Jasmien Hoebeeck, Frank Speleman, and Jo Vandesompele
Methods in Molecular Biology, vol. 353: 205-226
Protocols for Nucleic Acid Analysis by Nonradioactive Probes, Second Edition Edited by: E. Hilario and J. Mackay

Robust quantification of the SMN gene copy number by real-time TaqMan PCR.
Ilsa Gómez-Curet & Karyn G. Robinson & Vicky L. Funanage & Thomas O. Crawford & Mena Scavina & Wenlan Wang
Neurogenetics (2007) 8:271–278

An accurate method for quantifying and analyzing copy number variation in porcine KIT by an oligonucleotide ligation assay.
Bo-Young Seo, Eung-Woo Park, Sung-Jin Ahn, Sang-Ho, Jae-Hwan Kim, Hyun-Tae Im, Jun-Heon Lee, In-Cheol Cho, Il-Keun Kong and Jin-Tae Jeon
BMC Genetics (2007) 8:81

Large-Scale Copy Number Polymorphism in the Human Genome.
Jonathan Sebat, B. Lakshmi, Jennifer Troge, Joan Alexander, Janet Young, Par Lundin, Susanne Maner, Hillary Massa, Megan Walker, Maoyen Chi, Nicholas Navin, Robert Lucito, John Healy, James Hicks, Kenny Ye, Andrew Reiner, T. Conrad Gilliam, Barbara Trask, Nick Patterson, Anders Zetterberg, Michael Wigler
SCIENCE (2004) VOL 305 525-528

Major changes in our DNA lead to major changes in our thinking.
Jonathan Sebat

Accurate and reliable high-throughput detection of copy number variation in the human genome.
Heike Fiegler, Richard Redon, Dan Andrews, Carol Scott, Robert Andrews, Carol Carder, Richard Clark, Oliver Dovey, Peter Ellis, Lars Feuk, Lisa French, Paul Hunt,1 Dimitrios Kalaitzopoulos, James Larkin, Lyndal Montgomery, George H. Perry, Bob W. Plumb, Keith Porter, Rachel E. Rigby, Diane Rigler, Armand Valsesia, Cordelia Langford, Sean J. Humphray, Stephen W. Scherer, Charles Lee, Matthew E. Hurles, and Nigel P. Carter
Genome Research (2006) 16:1566–1574

Relevance of BAC transgene copy number in mice: transgene copy number variation across multiple transgenic lines and correlations with transgene integrity and expression.
Kelly J. Chandler Ronald L. Chandler Eva M. Broeckelmann Yue Hou E. Michelle Southard-Smith Douglas P. Mortlock
Mamm Genome (2007) 18: 693–708

Detection of large-scale variation in the human genome.
A John Iafrate, Lars Feuk, Miguel N Rivera, Marc L Listewnik, Patricia K Donahoe, Ying Qi, Stephen W Scherer & Charles Lee

Multiplex PCR-Based Real-Time Invader Assay (mPCR-RETINA): A Novel SNP-Based Method for Detecting Allelic Asymmetries Within Copy Number Variation Regions.
Naoya Hosono, Michiaki Kubo, Yumiko Tsuchiya, Hiroko Sato, Takuya Kitamoto, Susumu Saito, Yozo Ohnishi, and Yusuke Nakamura
HUMAN MUTATION (2007) 0,1-8

Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue.
M. Kaaman & L. M. Sparks & V. van Harmelen & S. R. Smith & E. Sjölin & I. Dahlman & P. Arner
Diabetologia (2007) 50: 2526–2533

Genome assembly comparison identifies structural variants in the human genome.
Razi Khaja, Junjun Zhang, Jeffrey R MacDonald, Yongshu He, Ann M Joseph-George, John Wei, Muhammad A Rafiq, Cheng Qian, Mary Shago, Lorena Pantano, Hiroyuki Aburatani, Keith Jones, Richard Redon, Matthew Hurles, Lluis Armengol, Xavier Estivill, Richard J Mural, Charles Lee, Stephen W Scherer & Lars Feuk
NATURE GENETICS (2006) VOLUME 38 NUMBER 12 1413-1418

Estrogen receptor alpha mRNA copy numbers in immunohistochemically ERα-positive-, and negative breast cancer tissues.
Indira Poola and Qingqi Yue
BMC Cancer 2007, 7: 56-66

Genome wide measurement of DNA copy number changes in neuroblastoma: dissecting amplicons and mapping losses, gains and breakpoints.
E. Michels, J. Vandesompele, J. Hoebeeck, B. Menten, K. De Preter, G. Laureys, N. Van Roy, F. Speleman
Cytogenet Genome Res (2006) 115: 273–282

Stochastic mRNA Synthesis in Mammalian Cells.
Arjun Raj, Charles S. Peskin, Daniel Tranchina, Diana Y. Vargas, Sanjay Tyagi
PLOS (2006) Volume 4 Issue 10 e309

Sensitive and Specific Real-Time Polymerase Chain Reaction Assays to Accurately Determine Copy Number Variations (CNVs) of Human Complement C4A, C4B, C4-Long, C4-Short, and RCCX Modules: Elucidation of C4 CNVs in 50 Consanguineous Subjects with Defined HLA Genotypes1.
Yee Ling Wu, Stephanie L. Savelli, Yan Yang, Bi Zhou, Brad H. Rovin, Daniel J. Birmingham, Haikady N. Nagaraja, Lee A. Hebert, and C. Yung Yu
The Journal of Immunology (2007) 179: 3012–3025

Development of bioinformatics resources for display and analysis of copy number and other structural variants in the human genome.
J. Zhang, L. Feuk, G.E. Duggan, R. Khaja, S.W. Scherer
Cytogenet Genome Res (2006) 115:205–214

Absolute and relative QPCR quantification of plasmid copy number in Escherichia coli.
Changsoo Lee, Jaai Kim, Seung Gu Shin, Seokhwan Hwang
Journal of Biotechnology (2006) 123: 273–280