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Vol. 68, No. 1, 2009
Issue release date: April 2009
Section title: Original Paper
Free Access
Hum Hered 2009;68:1–22

Markov Models for Inferring Copy Number Variations from Genotype Data on Illumina Platforms

Wang H.a · Veldink J.H.e · Blauw H.e · van den Berg L.H.e · Ophoff R.A.b, c, f · Sabatti C.b, d
aDepartment of Biostatistics, University of California at Berkeley, Berkeley, bDepartment of Human Genetics, cSemel Institute, and dDepartment of Statistics, UCLA, Los Angeles, Calif., USA; Departments of eNeurology and fMedical Genetics, University of Utrecht, Utrecht, The Netherlands
email Corresponding Author

Hui Wang

Department of Biostatistics

101 Havilard Hall, University of California at Berkeley

94720-7358, Berkeley, CA (USA)

Tel. +1 510 642 3241, Fax +1 510 643 5163, E-Mail


  1. Blauw H, Veldink J, van Es M, van Vught P, Saris C, van der Zwaag B, Frank L, Burbach P, Wokke J, Ophoff R, van der Berg L: Copy number variation in sporadic amyotrophic lateral sclerosis: a genome-wide screen. Lancet Neurol 2008;7:319–326.
  2. Colella S, Yau C, Taylor JM, Mirza G, Butler H, Clouston P, Bassett AS, Seller A, Holmes CC, Ragoussis J: QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucleic Acids Res 2007;35:2013–2025.
  3. Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK: A high-resolution survey of deletion polymorphism in the human genome. Nat Genet 2006;38:75–81.
  4. Diskin SJ, Eck T, Greshock J, Mosse YP, Naylor T, Stoeckert CJ Jr, Weber BL, Maris JM, Grant GR: STAC: A method for testing the significance of DNA copy number aberrations across multiple array-CGH experiments. Genome Res 2006;16:1149–1158.
  5. Hehir-Kwa JY, Egmont-Petersen M, Janssen IM, Smeets D, van Kessel AG, Veltman JA: Genome-wide copy number profiling on high-density bacterial artificial chromosomes, single-nucleotide polymorphisms, and oligonucleotide microarrays: A platform comparison based on statistical power analysis. DNA Res 2007;14:1–11.
  6. Iafrate AJ, Feuk L, Rivera MN, Listewnik ML, Donahoe PK, Qi Y, Scherer SW, Lee C: Detection of large-scale variation in the human genome. Nat Genet 2004;36:949–951.
  7. Lange K: Applied Probability. Springer, New York, 2004.
  8. Lange K: Optimization. Springer, New York, 2004.
  9. Newton M, Gould M, Reznikoff C, Haag J: On the statistical analysis of allelic-loss data. Stat Med 1998;17:1425–1445.
  10. Newton M, Lee Y: Inferring the location and effect of tumor suppressor genes by instability-selection modeling of allelic-loss data. Biometrics 2000;56:1088–1097.
  11. Newton MA: Discovering combinations of genomic alterations associated with cancer. J Am Stat Ass 2002;97:931–942.
    External Resources
  12. Peiffer D, Le J, Steemers F, Chang W, Jenniges T, Garcia F, Haden K, Li J, Shaw C, Belmont J, Cheung S, Shen R, Barker D, Gunderson K: High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping. Genome Res 2006;16:1136–1148.
  13. Perry GH, Tchinda J, McGrath SD, Zhang J, Picker SR, Caceres AM, Iafrate AJ, Tyler-Smith C, Scherer SW, Eichler EE, Stone AC, Lee C: Hotspots for copy number variation in chimpanzees and humans. Proc Natl Acad Sci 2006;103:8006–8011.
  14. Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, Gonzalez JR, Gratacos M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A, Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW, Hurles ME: Global variation in copy number in the human genome. Nature 2006;444:444–454.
  15. Sabatti C, Lange K: Bayesian Gaussian mixture models for high density genotyping arrays. JASA 2007;103:89–100.
    External Resources
  16. Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P, Maner S, Massa H, Walker M, Chi M, Navin N, Lucito R, Healy J, Hicks J, Ye K, Reiner A, Gilliam TC, Trask B, Patterson N, Zetterberg A, Wigler M: Large-scale copy number polymorphism in the human genome. Science 2004;305:525–528.
  17. Stefansson H, et al: Large recurrent microdeletions associated with schizophrenia. Nature 2008;455:232–236.
  18. Tang H, Coram M, Wang P, Zhu X, Risch N: Reconstructing genetic ancestry blocks in admixed individuals. Am J Hum Genet 2006;79:1–12.
  19. Tibshirani HR, Wang P: Spatial smoothing and hot spot detection for CGH data using the Fused Lasso. Biostatistics 2008;9:18–29.
  20. van Es MA, Van Vught PW, Blauw HM, Franke L, Saris CG, Andersen PM, Van Den Bosch L, de Jong SW, van’t Slot R, Birve A, Lemmens R, de Jong V, Baas F, Schelhaas HJ, Sleegers K, Van Broeckhoven C, Wokke JH, Wijmenga C, Robberecht W, Veldink JH, Ophoff RA, van den Berg LH: ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol 2007;6:869–877.
  21. van Es MA, van Vught PW, Blauw HM, Franke L, Saris CG, Van den Bosch L, de Jong SW, de Jong V, Baas F, van’t Slot R, Lemmens R, Schelhaas HJ, Birve A, Sleegers K, Van Broeckhoven C, Schymick JC, Traynor BJ, Wokke JH, Wijmenga C, Robberecht W, Andersen PM, Veldink JH, Ophoff RA, van den Berg LH: Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. Nat Genet 2008;40:29–31.
  22. Wang H, Lee Y, Nelson S, Sabatti C: Inferring genomic loss and location of tumor suppressor genes from high density genotypes. J French Stat Soc 2005;146:153–171.
  23. Wang H, Lin C, Service S, The international collaborative group on isolated populations, Chen Y, Freimer N, Sabatti C: Linkage disequilibrium and haplotype homozygosity in population samples genotyped at a high marker density. Hum Hered 2006;62:175–189.
  24. Wang K, Li M, Hadley D, Liu R, Glessner J, Grant S, Hakonarson H, Bucan M: PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res 2007;17:1665–1674.
  25. Diskin SJ, Li M, Hou C, Yang S, Glessner J, Hakonarson H, Bucan M, Maris JM, Wang K: Adjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms. Nucleic Acids Res 2008;36:e126. Epub 2008 Sept 10.