Advertisement

Copy Number Variants

  • Herman E. Wyandt
  • Vijay S. Tonk
Chapter

Abstract

The progression of cytogenetics from banded chromosomes to DNA segment dosage as detected by comparative genomic hybridization-microarray analysis (aCGH, also abbreviated as CMA) has greatly increased the frequency of positive findings and difficulties of interpretation. The technique of aCGH (Fig. 32.1) involves labeling patient and control DNA with different fluorochromes, hybridizing them to 40,000–1 million DNA segments arrayed on a glass slide or “DNA chip,” and comparing the extent of patient and control DNA hybridization signal amplitudes for each segment (Lee et al., Nature Genet suppl 39:S48–S54, 2007; Carter, Nature Genet suppl 39:S16–S21, 2007;Feuk et al., Hum Molec Genet 15:R57–R66, 1998). The DNA segments serving as probes are chosen to represent the entire genome extending through chromosomes 1–22, X, and Y, allowing graphing of hybridization signals according to chromosome band and base pair coordinates (see examples in patient discussions below). Departures of hybridization ratios from equivalency indicate duplication (patient signal greater than control) or deletion (patient signal less than control), and the number of contiguous DNA segments showing signal alterations define the extent of duplication or deletion by reference to their coordinates in the human genome sequence.

Keywords

Intellectual Disability Williams Syndrome Autism Disorder Angelman Syndrome Mental Disability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Lee C, Iafrate A, Brothman AR (2007) Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nature Genet suppl 39:S48–S54CrossRefGoogle Scholar
  2. 2.
    Carter NP (2007) Methods and strategies for analyzing copy number variation using DNA microarrays. Nature Genet suppl 39:S16–S21CrossRefGoogle Scholar
  3. 3.
    Feuk L, Marshall CR, Wintle RF, Scherer SW (2006) Structural variants: changing the landscape of chromosomes and the design of disease studies. Hum Molec Genet 15:R57–R66PubMedCrossRefGoogle Scholar
  4. 4.
    Lupski JR (1998) Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet 14:417–422PubMedCrossRefGoogle Scholar
  5. 5.
    Sebat J, Lakshmi B, Troge J et al (2004) Large—scale copy number polymorphisms in the human genome. Science 305:525–528PubMedCrossRefGoogle Scholar
  6. 6.
    Freeman JL, Perry GH, Feuk L et al (2006) Copy number variation: new insights in genome diversity. Genome Research 16:949–961PubMedCrossRefGoogle Scholar
  7. 7.
    Kaiser-Rogers K, Rao K (2009) Structural chromosome rearrangements. In: Gersen SL, Keagle MB (eds) Principles of clinical cytogenetics, 2nd edn. Human, Totowa, pp 165–206Google Scholar
  8. 8.
    Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JPT, Burton H (2009) Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13926 subjects. Genet Med 11:139–146PubMedCrossRefGoogle Scholar
  9. 9.
    Miller DT, Adam MP, Aradhya S et al (2010) Consensus Statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86:749–764PubMedCrossRefGoogle Scholar
  10. 10.
    Web Resources: http://cibex.nig.ac.jp/index.jsp, UC Santa Clara genome browser: http://genome.ucsc.edu/, Decipher: https://decipher.sanger.ac.uk/application/, http://projects.tcag.ca/variation/, http://www.ncbi.nlm.nih.gov/projects/SNP/, http://humanparalogy.gs.washington.edu/structuralvariation/, http://uswest.ensembl.org/index.html, http://www.ncbi.nlm.nih.gov/geo/, http://www.genenames.org/ http://humanparalogy.gs.washington.edu/; http://ccr.coriell.org/Sections/Collections/NIGMS/?SsId =8; http://projects.tcag.ca/humandup/, http://www.ncbi.nlm.nih.gov/unigeneGoogle Scholar
  11. 11.
    Scambler PJ (2010) 22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development. Pediatr Cardiol 31:373–390CrossRefGoogle Scholar
  12. 12.
    Gothelf D, Schaer M, Eliez S (2008) Genes, brain development and psychiatric phenotypes in velo-cardio-facial syndrome. Dev Disabil Res Rev 14:59–68PubMedCrossRefGoogle Scholar
  13. 13.
    Brunetti-Pierri MG, Micale L, Fusco C (2010) Copy number variants at Williams-Beuren syndrome 7q11.23 region. Hum Genet 128:3–26PubMedCrossRefGoogle Scholar
  14. 14.
    Tatton-Brown K, Cole TRP, Rahman N (2009) Sotos syndrome In: Pagon RA, Bird TC, Dolan CR, Stephens K, eds. Gene Reviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2004 Dec 17 (Updated 2009 Dec 10)Google Scholar
  15. 15.
    Weiss LA, Shen Y, Korn JM et al (2008) Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 358:667–675PubMedCrossRefGoogle Scholar
  16. 16.
    Ben-Schachar S, Lanpher B, German JR et al (2009) Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J Med Genet 46:382–88CrossRefGoogle Scholar
  17. 17.
    Van Esch H, Hollanders K, Badisco L, Melotte C, Van Hummelen P, Vermeesch JR, Devriendt K, Fryns JP, Marynen P, Froyen G (2005) Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis. Hum Mol Genet 14:1795–1803PubMedCrossRefGoogle Scholar
  18. 18.
    Stevens CA (2009) Rubinstein-Taybe syndrome In: Pagon RA, Bird TC, Dolan CR, Stephens K, (eds) Gene Reviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2002 Aug 30 (Updated 2009 Aug 20)Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Boston University School of Medicine Center for Human GeneticsBostonUSA
  2. 2.Acupath Laboratories, Inc.PlainviewUSA
  3. 3.Department of PediatricsTexas Tech University Health Science CenterLubbockUSA

Personalised recommendations