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

 goto top of outline Key Words

  • Linkage
  • Disequilibrium association

 goto top of outline Abstract

Background/Aims: Illumina genotyping arrays provide information on DNA copy number. Current methodology for their analysis assumes linkage equilibrium across adjacent markers. This is unrealistic, given the markers high density, and can result in reduced specificity. Another limitation of current methods is that they cannot be directly applied to the analysis of multiple samples with the goal of detecting copy number polymorphisms and their association with traits of interest. Methods: We propose a new Hidden Markov Model for Illumina genotype data, that takes into account linkage disequilibrium between adjacent loci. Our framework also allows for location specific deletion/duplication rates. When multiple samples are available, we describe a methodology for their analysis that simultaneously reconstructs the copy number states in each sample and identifies genomic locations with increased variability in copy number in the population. This approach can be extended to test association between copy number variants and a disease trait. Results and Conclusions: We show that taking into account linkage disequilibrium between adjacent markers can increase the specificity of a HMM in reconstructing copy number variants, especially single copy deletions. Our multisample approach is computationally practical and can increase the power of association studies.

Copyright © 2009 S. Karger AG, Basel

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 goto top of outline Author Contacts

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 hwangui@berkeley.edu

 goto top of outline Article Information

Received: February 28, 2008
Accepted after revision: October 13, 2008
Published online: April 1, 2009
Number of Print Pages : 22
Number of Figures : 12, Number of Tables : 6, Number of References : 25

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 68, No. 1, Year 2009 (Cover Date: April 2009)

Journal Editor: Devoto M. (Philadelphia, Pa.)
ISSN: 0001-5652 (Print), eISSN: 1423-0062 (Online)

For additional information: http://www.karger.com/HHE

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