Gene copy number

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Gene copy number (also called "copy number variants"(CNVs), or "copy number polymorphisms"(CNPs)) refers to the genetic trait of differences in the number of copies of a particular gene present in the genome of an individual. The fact that differences in the number of copies of certain genes contributes to genetic variability within humans was uncovered following the completion of the human genome project. Some people have deletions of some genes on only one chromosome while other people have multiple copies of some genes. Out of about 20,000 human genes, unrelated people typically have different copy numbers at about 12 sites, and the size of large-scale differences ranges from a few kilobases to 2 megabases.^[1]^[2]

Like other types of genetic variation, some gene copy number variants have been identified as carrying susceptibility or resistance to disease. Gene copy number can be elevated in cancer cells. For instance, the EGFR copy number can be higher than normal in Non-small cell lung cancer.^[3] In addition, higher copy number of CCL3L1 has been associated with lower susceptibility to human HIV infection^[4], and low copy number of FCGR3B (the CD16 cell surface immunoglobulin receptor) can increase susceptibility to Systemic Lupus Erythematosus and similar inflammatory immune system disorders.^[5] In man, these large-scale copy number variants encompass as much DNA as the many single nucleotide polymorphisms (SNPs) and may be responsible for a similar amount of phenotypic variability and disease susceptibility. ^[6]

In certain cases, such as rapidly growing Escherichia coli cells, the gene copy number can be 4-fold greater for genes located near the origin of DNA replication, rather than at the terminus of DNA replication. Elevating the gene copy number of a particular gene can increase the expression of the protein that it encodes.^[7]

[edit] Sources and notes

^ Sebat J, et al. (2004). "Large-scale copy number polymorphism in the human genome". Science 305: 525–528. doi:10.1126/science.1098918. PMID 15273396.
^ Iafrate A, et al. (2004). "Detection of large-scale variation in the human genome.". Nature Genetics 36: 949-51. doi:10.1038/ng1416. PMID 15286789.
^ Cappuzzo F, Hirsch, et al. (2005). "Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer". Journal of the National Cancer Institute 97: 643–655. doi:10.1093/jnci/dji112.
^ Gonzalez, E. et al. (2005). "The Influence of CCL3L1 Gene-Containing Segmental Duplications on HIV-1/AIDS Susceptibility". Science 307: 1434–1440. doi:10.1126/science.1101160. PMID 15637236.
^ Aitman T. J. et al. (2006). "Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans". Nature 439: 851–855. doi:10.1038/nature04489. PMID 16482158.
^ Redon, J. et al (2006). "Global variation in copy number in the human genome". Nature 444: 444–454. doi:10.1038/nature05329. PMID 17122850.
^ Atkinson M, Savageau M, Myers JT, Ninfa A (2003). "Development of Genetic Circuitry Exhibiting Toggle Switch Behavior in Escherichia Coli". Cell 113: 597. doi:10.1016/S0092-8674(03)00346-5. PMID 12787501.

Freeman, JL, et al (2006). "Copy number variation: New insights into genome diversity". Genome Research 16: 949–61. doi:10.1101/gr.3677206. PMID 16809666.

[edit] Further reading

Genome-wide analysis of DNA copy-number changes using cDNA microarrays "Gene amplifications and deletions frequently contribute to tumorigenesis. Characterization of these DNA copy-number changes is important for both the basic understanding of cancer and its diagnosis."
Gene duplications may define who you are. New Scientist (November 22, 2006).

Two separate studies of the human genome have revealed an unsuspected amount of variation between people in the number of copies of genes they have. [...] They discovered that nearly 24 million nucleotides are involved in such copy number variants (CNVs). [...] They found 1447 CNVs, covering about 12% of the human genome."