Mathematical Analysis of Copy Number Variation in a DNA Sample Using Digital PCR on a Nanofluidic Device

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Aug 7

PMID 18682853

Citations 120

Authors

Simant Dube

Jian Qin

Ramesh Ramakrishnan

Affiliations

Soon will be listed here.

Abstract

Copy Number Variations (CNVs) of regions of the human genome have been associated with multiple diseases. We present an algorithm which is mathematically sound and computationally efficient to accurately analyze CNV in a DNA sample utilizing a nanofluidic device, known as the digital array. This numerical algorithm is utilized to compute copy number variation and the associated statistical confidence interval and is based on results from probability theory and statistics. We also provide formulas which can be used as close approximations.

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References

Emery S, Erdman D, Bowen M, Newton B, Winchell J, Meyer R . Real-time reverse transcription-polymerase chain reaction assay for SARS-associated coronavirus. Emerg Infect Dis. 2004; 10(2):311-6. PMC: 3322901. DOI: 10.3201/eid1002.030759. View

Lupski J . Genomic rearrangements and sporadic disease. Nat Genet. 2007; 39(7 Suppl):S43-7. DOI: 10.1038/ng2084. View

Vogelstein B, Kinzler K . Digital PCR. Proc Natl Acad Sci U S A. 1999; 96(16):9236-41. PMC: 17763. DOI: 10.1073/pnas.96.16.9236. View

Wong K, deLeeuw R, Dosanjh N, Kimm L, Cheng Z, Horsman D . A comprehensive analysis of common copy-number variations in the human genome. Am J Hum Genet. 2006; 80(1):91-104. PMC: 1785303. DOI: 10.1086/510560. View

Sindelka R, Jonak J, Hands R, Bustin S, Kubista M . Intracellular expression profiles measured by real-time PCR tomography in the Xenopus laevis oocyte. Nucleic Acids Res. 2007; 36(2):387-92. PMC: 2241880. DOI: 10.1093/nar/gkm1024. View

Sebat J, Lakshmi B, Troge J, Alexander J, Young J, Lundin P . Large-scale copy number polymorphism in the human genome. Science. 2004; 305(5683):525-8. DOI: 10.1126/science.1098918. View

Spurgeon S, Jones R, Ramakrishnan R . High throughput gene expression measurement with real time PCR in a microfluidic dynamic array. PLoS One. 2008; 3(2):e1662. PMC: 2244704. DOI: 10.1371/journal.pone.0001662. View

Carter N . Methods and strategies for analyzing copy number variation using DNA microarrays. Nat Genet. 2007; 39(7 Suppl):S16-21. PMC: 2697494. DOI: 10.1038/ng2028. View

Ropers H . New perspectives for the elucidation of genetic disorders. Am J Hum Genet. 2007; 81(2):199-207. PMC: 1950818. DOI: 10.1086/520679. View

10.

Baer M, Nilsen T, Costigan C, Altman S . Structure and transcription of a human gene for H1 RNA, the RNA component of human RNase P. Nucleic Acids Res. 1990; 18(1):97-103. PMC: 330208. DOI: 10.1093/nar/18.1.97. View

11.

Iafrate A, Feuk L, Rivera M, Listewnik M, Donahoe P, Qi Y . Detection of large-scale variation in the human genome. Nat Genet. 2004; 36(9):949-51. DOI: 10.1038/ng1416. View

12.

Lo Y, Lun F, Chan K, Tsui N, Chong K, Lau T . Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proc Natl Acad Sci U S A. 2007; 104(32):13116-21. PMC: 1934923. DOI: 10.1073/pnas.0705765104. View

13.

Redon R, Ishikawa S, Fitch K, Feuk L, Perry G, Andrews T . Global variation in copy number in the human genome. Nature. 2006; 444(7118):444-54. PMC: 2669898. DOI: 10.1038/nature05329. View