Review article

You have full text access to this OnlineOpen article

The impact of human copy number variation on a new era of genetic testing

  1. KW Choy1,2,
  2. SR Setlur3,
  3. C Lee3,
  4. TK Lau2

Article first published online: 26 JAN 2010

DOI: 10.1111/j.1471-0528.2009.02470.x

Issue

BJOG: An International Journal of Obstetrics & Gynaecology

BJOG: An International Journal of Obstetrics & Gynaecology

Volume 117, Issue 4, pages 391–398, March 2010

Additional Information

How to Cite

Choy, K., Setlur, S., Lee, C. and Lau, T. (2010), The impact of human copy number variation on a new era of genetic testing. BJOG: An International Journal of Obstetrics & Gynaecology, 117: 391–398. doi: 10.1111/j.1471-0528.2009.02470.x

Author Information

  1. 1

    Department of Obstetrics & Gynaecology,

  2. 2

    Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China

  3. 3

    Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

*Dr KW Choy, 1E, Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. Email richardchoy@cuhk.edu.hk

Publication History

  1. Issue published online: 8 FEB 2010
  2. Article first published online: 26 JAN 2010
  3. Accepted 15 November 2009. Published Online 26 January 2010.

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (175K)

References

  • 1
    Scherer SW, Lee C, Birney E, Altshuler DM, Eichler EE, Carter NP, et al. Challenges and standards in integrating surveys of structural variation. Nat Genet 2007;39:S7–15.
  • 2
    Tepperberg J, Pettenati MJ, Rao PN, Lese CM, Rita D, Wyandt H, et al. Prenatal diagnosis using interphase fluorescence in situ hybridization (FISH):2-year multi-center retrospective study and review of the literature. Prenat Diagn 2001;21:293–301.
    Direct Link:
  • 3
    Evans MI, Henry GP, Miller WA, Bui TH, Sniders RJ, Wapner RJ, et al. International, collaborative assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used. Hum Reprod 1999;14:1213–6.
  • 4
    Choy KW, Tsang PT, Leung TY, Wang CC, Lau TK. The application of microarray based comparative genomic hybridization in prenatal diagnosis. Fetal Matern Med Rev 2008;19:119–33.
  • 5
    Hulten MADS, Pertl B. Rapid and simple prenatal diagnosis of common chromosome disorders: advantages and disadvantages of the molecular methods FISH and QF-PCR. Reproduction 2003;126:279–97.
  • 6
    McCarroll SA, Altshuler DM. Copy-number variation and association studies of human disease. Nat Genet 2007;39:S37–42.
  • 7
    Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, et al. Detection of large-scale variation in the human genome. Nat Genet 2004;36:949–51.
  • 8
    Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, et al. Large-scale copy number polymorphism in the human genome. Science 2004;305:525–8.
  • 9
    Tuzun E, Sharp AJ, Bailey JA, Kaul R, Morrison VA, Pertz LM, et al. Fine-scale structural variation of the human genome. Nat Genet 2005;37:727–32.
  • 10
    Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK. A highresolution survey of deletion polymorphism in the human genome. Nat Genet 2005;38:75–81.
  • 11
    McCarroll SA, Hadnott TN, Perry GH, Sabeti PC, Zody MC, Barrett J, et al. Common deletion variants in the human genome. Nat Genet 2006;38:86–92.
  • 12
    Redon R, Ishikawa S, Fitch KR, Feuk L, Perry G, Andrews TD, et al. Global variation in copy number in the human genome. Nature 2006;444:444–54.
  • 13
    Lu X, Shaw CA, Patel A, Li J, Cooper ML, Wells WR, et al. Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases. PLoS ONE 2007;2:e327.
  • 14
    Edelmann L, Hirschhorn K. Clinical utility of array CGH for the detection of chromosomal imbalances associated with mental retardation and multiple congenital anomalies. Ann N Y Acad Sci 2009;1151:157–66.
    Direct Link:
  • 15
    Bi W, Breman AM, Venable SF, Eng PA, Sahoo T, Lu XY, et al. Rapid prenatal diagnosis using uncultured amniocytes and oligonucleotide array CGH. Prenat Diagn 2008;28:943–9.
    Direct Link:
  • 16
    Law LW, Lau TK, Fung TY, Leung TY, Wang CC, Choy KW. De novo 16p13.11 microdeletion identified by high resolution array CGH in a fetus with increased nuchal translucency. BJOG 2009;116:339–43.
    Direct Link:
  • 17
    Rickman L, Fiegler H, Shaw-Smith C, Nash R, Cirigliano V, Voglino G, et al. Prenatal detection of unbalanced chromosomal rearrangements by array CGH. J Med Genet 2006;43:353–61.
  • 18
    Roa BB, Pulliam J, Eng CM, Cheung SW. Evolution of prenatal genetics: from point mutation testing to chromosomal microarray analysis. Expert Rev Mol Diagn 2005;5:883–92.
  • 19
    Sahoo T, Cheung SW, Ward P, Darilek S, Patel A, del Gaudio D, et al. Prenatal diagnosis of chromosomal abnormalities using array-based comparative genomic hybridization. Genet Med 2006;8:719–27.
  • 20
    Van den Veyver IB, Patel A, Shaw CA, Pursley AN, Kang SH, Simovich MJ, et al. Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300 cases. Prenat Diagn 2009;29:29–39.
    Direct Link:
  • 21
    Feuk L, Marshall CR, Wintle RF, Scherer SW. Structural variants: changing the landscape of chromosomes and design of disease studies. Hum Mol Genet 2006;1:R57–66.
  • 22
    Freeman JL, Perry GH, Feuk L, Redon R, McCarroll SA, Altshuler DM, et al. Copy number variation: new insights in genome diversity. Genome Res 2006;16:949–61.
  • 23
    McCarroll SA, Kuruvilla FG, Korn JM, Cawley S, Nemesh J, Wysoker A, et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat Genet 2008;40:1166–74.
  • 24
    Perry GH, Ben-Dor A, Tsalenko A, Sampas N, Rodriguez-Revenga L, Tran CW, et al. The fine-scale and complex architecture of human copy-number variation. Am J Hum Genet 2008;82:685–95.
  • 25
    Zogopoulos G, Ha KC, Naqib F, Moore S, Kim H, Montpetit A, et al. Germ-line DNA copy number variation frequencies in a large North American population. Hum Genet 2007;122:345–53.
  • 26
    Henrichsen CN, Chaignat E, Reymond A. Copy number variants, diseases and gene expression. Hum Mol Genet 2009;18(R1):R1-8.
  • 27
    Shaw CJ, Lupski JR. Implications of human genome architecture for rearrangement-based disorders: the genomic basis of disease. Hum Mol Genet 2004;13:R57–64.
  • 28
    Shaffer LG, Lupski JR. Molecular mechanisms for constitutional chromosomal rearrangements in humans. Annu Rev Genet 2000;34:297–329.
  • 29
    Hastings PJ, Ira G, Lupski JR. A microhomology-mediated break-induced replication model for the origin of human copy number variation. PLoS Genet. 2009;5:e1000327.
  • 30
    Hastings PJ, Lupski JR, Rosenberg SM, Ira G. Mechanisms of change in gene copy number. Nat Rev Genet 2009;10:551–64.
  • 31
    Lee JA, Carvalho CM, Lupski JR. A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders. Cell 2007;131:1235–47.
  • 32
    Liu G, Van Tassell CP, Sonstegard TS, Li RW, Alexander LJ, Keele JW, et al. Detection of germline and somatic copy number variations in cattle. Dev Biol (Basel) 2008;132:231–7.
  • 33
    Piotrowski A, Bruder CE, Andersson R, de Ståhl TD, Menzel U, Sandgren J, et al. Somatic mosaicism for copy number variation in differentiated human tissues. Hum Mutat 2008;29:1118–24.
    Direct Link:
  • 34
    Bruder CE, Piotrowski A, Gijsbers AA, Andersson R, Erickson S, de Ståhl TD, et al. Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 2008;82:763–71.
  • 35
    Sebat J. Major changes in our DNA lead to major changes in our thinking. Nat Genet 2007;39:S3–5.
  • 36
    Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J, Benner A, Döhner H, et al. Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 1997;20:399–407.
    Direct Link:
  • 37
    Cooper GM, Zerr T, Kidd JM, Eichler EE, Nickerson DA. Systematic assessment of copy number variant detection via genome-wide SNP genotyping. Nat Genet 2008;40:1199–203.
  • 38
    Pinto D, Marshall C, Feuk L, Scherer SW. Copy-number variation in control population cohorts. Hum Mol Genet 2007;16 Spec No 2:R168–73.
  • 39
    Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 2005;77:442–53.
  • 40
    Aitman TJ, Dong R, Vyse TJ, Norsworthy PJ, Johnson MD, Smith J, et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 2006;439:851–5.
  • 41
    Fanciulli M, Norsworthy PJ, Petretto E, Dong R, Harper L, Kamesh L, et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat Genet 2007;39:721–3.
  • 42
    Mamtani M, Rovin B, Brey R, Camargo JF, Kulkarni H, Herrera M, et al. CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Ann Rheum Dis 2008;67:1076–83.
  • 43
    Yang Y, Chung EK, Wu YL, Savelli SL, Nagaraja HN, Zhou B, et al. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. Am J Hum Genet 2007;80:1037–54.
  • 44
    Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al. alpha-Synuclein locus triplication causes Parkinson’s disease. Science 2003;302:841.
  • 45
    Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S, et al. Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet 2004;364:1167–9.
  • 46
    Ibanez P, Bonnet AM, Debarges B, Lohmann E, Tison F, Pollak P, et al. Causal relation between alpha-synuclein gene duplication and familial Parkinson’s disease. Lancet 2004;364:1169–71.
  • 47
    Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 2006;79:439–48.
  • 48
    Hollox EJ, Huffmeier U, Zeeuwen PL, Palla R, Lascorz J, Rodijk-Olthuis D, et al. Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 2008;40:23–5.
  • 49
    Lachman HM, Pedrosa E, Petruolo OA, Cockerham M, Papolos A, Novak T, et al. Increase in GSK3beta gene copy number variation in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 2007;144B:259–65.
    Direct Link:
  • 50
    Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, et al. Strong association of de novo copy number mutations with autism. Science 2007;316:445–9.
  • 51
    International Schizophrenia Consortium. Collaborators Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 2008;455:237.
  • 52
    Stefansson H, Rujescu D, Cichon S, Pietiläinen OP, Ingason A, Steinberg S. Large recurrent microdeletions associated with schizophrenia. Nature 2008;455:232–6.
  • 53
    Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 2005;307:1434–40.
  • 54
    Borozdin W, Graham JM Jr, Bohm D, Bamshad MJ, Spranger S, Burke L, et al. Multigene deletions on chromosome 20q13.13-q13.2 including SALL4 result in an expanded phenotype of Okihiro syndrome plus developmental delay. Hum Mutat 2007;28:830.
    Direct Link:
  • 55
    Svensson AM, Curry CJ, South ST, Whitby H, Maxwell TM, Aston E, et al. Detection of a de novo interstitial 2q microdeletion by CGH microarray analysis in a patient with limb malformations, microcephaly and mental retardation. Am J Med Genet A 2007;143:1348–53.
  • 56
    Balikova I, Martens K, Melotte C, Amyere M, Van Vooren S, Moreau Y, et al. Autosomal-dominant microtia linked to five tandem copies of a copy-number-variable region at chromosome 4p16. Am J Hum Genet 2008;82:181–7.
  • 57
    Lee JA, Lupski JR. Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders. Neuron 2006;52:103–21. Review.
  • 58
    Diskin SJ, Hou C, Glessner JT, Attiyeh EF, Laudenslager M, Bosse K, et al. Copy number variation at 1q21.1 associated with neuroblastoma. Nature 2009;459:987–91.
  • 59
    Frank B, Bermejo JL, Hemminki K, Sutter C, Wappenschmidt B, Meindl A, et al. Copy number variant in the candidate tumor suppressor gene MTUS1 and familial breast cancer risk. Carcinogenesis 2007;28:1442–5.
  • 60
    Karypidis AH, Olsson M, Andersson SO, Rane A, Ekstrom L. Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate. Pharmacogenomics J 2008;8:147–51.
  • 61
    Park J, Chen L, Ratnashinge L, Sellers TA, Tanner JP, Lee JH, et al. Deletion polymorphism of UDP-glucuronosyltransferase 2B17 and risk of prostate cancer in African American and Caucasian men. Cancer Epidemiol Biomarkers Prev 2006;15:1473–8.
  • 62
    Gallagher CJ, Kadlubar FF, Muscat JE, Ambrosone CB, Lang NP, Lazarus P. The UGT2B17 gene deletion polymorphism and risk of prostate cancer. A case–control study in Caucasians. Cancer Detect Prev 2007;31:310–5.
  • 63
    Lee C, Iafrate AJ, Brothman AR. Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet 2007;39:S48–54.
  • 64
    Saifi GM, Szigeti K, Snipes GJ, Garcia CA, Lupski JR. Molecular mechanisms, diagnosis, and rational approaches to management of and therapy for Charcot-Marie-Tooth disease and related peripheral neuropathies. J Investig Med 2003;51:261–83.
  • 65
    De Gregori M, Ciccone R, Magini P, Pramparo T, Gimelli S, Messa J, et al. Cryptic deletions are a common finding in “balanced” reciprocal and complex chromosome rearrangements: a study of 59 patients. J Med Genet 2007;44:750–62.
  • 66
    Shaffer LG, Coppinger J, Alliman S, Torchia BA, Theisen A, Ballif BC, Bejjani BA. Comparison of microarray-based detection rates for cytogenetic abnormalities in prenatal and neonatal specimens. Prenat Diagn 2008;28:789.
    Direct Link:
  • 67
    Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Redon R, et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 2007;315:848–53.
  • 68
    Knight SJ, Regan R, Nicod A, Horsley SW, Kearney L, Homfray T, et al. Subtle chromasomal rearrangements in children with unexplained mental retardation. Lancet 1999;354:1676–81.
  • 69
    Bejjani BA, Saleki R, Ballif BC, Rorem EA, Sundin K, Theisen A, et al. Use of targeted array-based CGH for the clinical diagnosis of chromosomal imbalance: is less more? Am J Med Genet A 2005;134:259–67.
  • 70
    Wordsworth S, Buchanan J, Regan R, Smith K, Dyer S, Campbell C, et al. Diagnosing idiopathic learning disability: a cost-effectiveness analysis of microarray technology in the National Health Service of the United Kingdom. Genomic Med 2007;1:35–45.
View Full Article (HTML) Get PDF (175K)