Interpretation of Genomic Copy Number Variants Using DECIPHER

Manuel Corpas1, Eugene Bragin1, Stephen Clayton1, Paul Bevan1, Helen V. Firth2

1 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom, 2 Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 8.14
DOI:  10.1002/0471142905.hg0814s72
Online Posting Date:  January, 2012
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Many patients suffering from developmental disorders have submicroscopic deletions or duplications affecting the copy number of dosage‐sensitive genes or disrupting normal gene expression. Many of these changes are novel or extremely rare, making clinical interpretation problematic and genotype/phenotype correlations difficult. Identification of patients sharing a genomic rearrangement and having phenotypes in common increases certainty in the diagnosis and allows characterization of new syndromes. The DECIPHER database is an online repository of genotype and phenotype data whose chief objective is to facilitate the association of genomic variation with phenotype to enable the clinical interpretation of copy number variation (CNV). This unit shows how DECIPHER can be used to (1) search for consented patients sharing a defined chromosomal location, (2) navigate regions of interest using in‐house visualization tools and the Ensembl genome browser, (3) analyze affected genes and prioritize them according to their likelihood of haploinsufficiency, (4) upload patient aberrations and phenotypes, and (5) create printouts at different levels of detail. By following this protocol, clinicians and researchers alike will be able to learn how to characterize their patients' chromosomal imbalances using DECIPHER. Curr. Protoc. Hum. Genet. 72:8.14.1‐8.14.17 © 2012 by John Wiley & Sons, Inc.

Keywords: copy number variation; clinical genetics; array CGH; genotype; phenotype; developmental disorders; bioinformatics

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Table of Contents

  • Introduction
  • Basic Protocol 1: Searching DECIPHER by Location as a Public User
  • Basic Protocol 2: Searching DECIPHER for a Phenotype as a Public User
  • Basic Protocol 3: Adding a Patient to DECIPHER as a Registered Member
  • Commentary
  • Literature Cited
  • Figures
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Literature Cited

Literature Cited
   Baraitser, M., Tomiwa, K., Wilson, J., and Winter, R. 1989. A database of genetically determined neurological conditions for clinicians. J. Neurol. Neurosurg. Psychiatry 52:106.
   Bruford, E.A., Lush, M.J., Wright, M.W., Sneddon, T.P., Povey, S., and Birney, E. 2008. The HGNC Database in 2008: A resource for the human genome. Nucleic Acids Res. 36:D445‐D448.
   Conrad, D.F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T.D., Barnes, C., and Campbell, P. 2009. Origins and functional impact of copy number variation in the human genome. Nature 464:704‐712.
   Engels, H., Wohlleber, E., Zink, A., Hoyer, J., Ludwig, K.U., Brockschmidt, F.F., Wieczorek, D., Moog, U., Hellmann‐Mersch, B., and Weber, R.G. 2009. A novel microdeletion syndrome involving 5q14. 3‐q15: Clinical and molecular cytogenetic characterization of three patients. Eur. J. Hum. Genet. 17:1592‐1599.
   Firth, H.V. and Wright, C.F. 2011. The deciphering developmental disorders (DDD) study. Dev. Med. Child Neurol. 53:702‐703.
   Firth, H.V., Richards, S.M., Bevan, A.P., Clayton, S., Corpas, M., Rajan, D., Van Vooren, S., Moreau, Y., Pettett, R.M., and Carter, N.P. 2009. DECIPHER: Database of chromosomal imbalance and phenotype in humans using Ensembl resources. Am. J. Hum. Genet. 84:524‐533.
   Flicek, P., Amode, M., Barrell, D., Beal, K., Brent, S., Chen, Y., Clapham, P., Coates, G., Fairley, S., and Fitzgerald, S. 2010. Ensembl 2011. Nucleic Acids Res. 39:D800‐D806.
   Huang, N., Lee, I., Marcotte, E.M., Hurles, M.E., and Schierup, M.H.2010. Characterising and predicting haploinsufficiency in the human genome. PLoS Genet. 6:e1001154.
   Jaillard, S., Drunat, S., Bendavid, C., Aboura, A., Etcheverry, A., Journel, H., Delahaye, A., Pasquier, L., Bonneau, D., and Toutain, A. 2010. Identification of gene copy number variations in patients with mental retardation using array‐CGH: Novel syndromes in a large French series. Eur. J. Med. Genet. 53:66‐75.
   Le Meur, N., Holder‐Espinasse, M., Jaillard, S., Goldenberg, A., Joriot, S., Amati‐Bonneau, P., Guichet, A., Barth, M., Charollais, A., and Journel, H. 2010. MEF2C haploinsufficiency caused by either microdeletion of the 5q14. 3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations. J. Med. Genet. 47:22.
   Mills, R.E., Walter, K., Stewart, C., Handsaker, R.E., Chen, K., Alkan, C., Abyzov, A., Yoon, S.C., Ye, K., and Cheetham, R.K. 2011. Mapping copy number variation by population‐scale genome sequencing. Nature 470:59‐65.
   Robinson, P.N., Köhler, S., Bauer, S., Seelow, D., Horn, D., and Mundlos, S. 2008. The human phenotype ontology: A tool for annotating and analyzing human hereditary disease. Am. J. Hum. Genet. 83:610‐615.
   Sanborn, J., Benz, S., Craft, B., Szeto, C., Kober, K., Meyer, L., Vaske, C., Goldman, M., Smith, K., and Kuhn, R. 2010. The UCSC cancer genomics browser: Update 2011. Nucleic Acids Research. 39:D951‐D959.
   Stankiewicz, P. and Beaudet, A. 2007. Use of array CGH in the evaluation of dysmorphology, malformations, developmental delay, and idiopathic mental retardation. Curr. Opin. Genet. Dev. 17:182‐192.
   Winter, R.M. and Baraitser, M. 1987. The London Dysmorphology Database. J. Med. Genet. 24:509.
   Zweier, M., Gregor, A., Zweier, C., Engels, H., Sticht, H., Wohlleber, E., Bijlsma, E.K., Holder, S.E., Zenker, M., and Rossier, E. 2010. Mutations in MEF2C from the 5q14. 3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression. Hum. Mutat. 31:722‐733.
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