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Cited by 102Microfluidic and Capillary Electrophoresis ApplicationsGenomic variations and chromosomal abnormalitiesNanopore and Nanochannel Transport Studies

Studying copy number variations using a nanofluidic platform

Open access
Qin, Jian, Jones, Robert C., Ramakrishnan, Ramesh·2008·Nucleic Acids Research
DOI 10.1093/nar/gkn518PMC PMC2566873
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Abstract

Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). All these approaches are limited in resolution and can at best distinguish a twofold (or 50%) difference in copy number. We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples. We have evaluated the digital array's performance using a model system, to show that this technology is exquisitely sensitive, capable of differentiating as little as a 15% difference in gene copy number (or between 6 and 7 copies of a target gene). We have also analyzed commercial DNA samples for their CYP2D6 copy numbers and confirmed that our results were consistent with those obtained independently using conventional techniques. In a screening experiment with breast cancer and normal DNA samples, the ERBB2 gene was found to be amplified in about 35% of breast cancer samples. The use of the digital array enables accurate measurement of gene copy numbers and is of significant value in CNV studies.

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  • dPCR has shown promise for improving the limit of detection for nucleic acid quantification, with a number of reports highlighting superior accuracy of dPCR for CNV analysis.

    “One method that has shown promise for improving the limit of detection for nucleic acid quantification is digital PCR (dPCR) with a number of reports highlighting the superior accuracy of dPCR for CNV analysis (20,21).”

    From Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation (2012) · cites this paper as [20]

    The Abstract reports that the digital array distinguished a 15% difference in gene copy number, and the Discussion says it offered greater discrimination than quantitative PCR for CNV analysis. The paper does not establish an improved limit of detection for nucleic acid quantification; distinguishing small copy-number differences is not the same as detecting a lower amount of nucleic acid. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Qin and co-workers suggested that pre-amplification with gene-specific primers can overcome the problem of linked copies before dPCR.

    “Qin and co-workers (20) have suggested that this problem can be overcome by a pre-amplification step using gene-specific primers to separate the linked copies before performing dPCR.”

    From Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation (2012) · cites this paper as [20]

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Research works printed but not linked: 15

  1. [46]Masood S Bui MM Prognostic and predictive value of HER2/neu oncogene in breast cancer Microsc. Res. Tech. 2002 59 102 108 12373720
  2. [48]Eichler EE Recent duplication, domain accretion and the dynamic mutation of the human genome Trends Genet. 2001 17 661 669 11672867
  3. [49]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 15286789
  4. [50]Sebat J Lakshmi B Troge J Alexander J Young J Lundin P Månér S Massa H Walker M Chi M Large-scale copy number polymorphism in the human genome Science 2004 305 525 528 15273396
  5. [51]Sharp AJ Locke DP McGrath SD Cheng Z Bailey JA Vallente RU Pertz LM Clark RA Schwartz SR Segmental duplications and copy-number variation in the human genome Am. J. Hum. Genet 2005 77 78 88 15918152 PMC1226196
  6. [52]Feuk L Carson AR Scherer SW Structural variation in the human genome Nat. Rev. Genet. 2006 7 85 97 16418744
  7. [56]Ropers HH New perspectives for the elucidation of genetic disorders Am. J. Hum. Genet. 2007 81 199 207 17668371 PMC1950818
  8. [57]Lupski JR Genomic rearrangements and sporadic disease Nat. Genet. 2007 39 S43 47 17597781
  9. [58]Redon R Ishikawa S Fitch KR Feuk L Perry GH Andrews TD Fiegler H Shapero MH Carson AR Chen W Global variation in copy number in the human genome Nature 2006 444 444 454 17122850 PMC2669898
  10. [60]Scherer SW Lee C Birney E Altshuler DM Eichler EE Carter NP Hurles ME Feuk L Challenges and standards in integrating surveys of structural variation Nat. Genet. 2007 39 Suppl. 7 S7 S15 17597783 PMC2698291
  11. [61]Schaeffeler E Schwab M Eichelbaum M Zanger UM CYP2D6 genotyping strategy based on gene copy number determination by TaqMan real-time PCR Hum. Mutat. 2003 22 476 485 14635107
  12. [62]Bodin L Beaune PH Loriot MA Determination of cytochrome P450 2D6 (CYP2D6) gene copy number by real-time quantitative PCR J. Biomed. Biotechnol. 2005 2005 248 253 16192683 PMC1224698
  13. [63]Meijerman I Sanderson LM Smits PH Beijnen JH Schellens JH Pharmacogenetic screening of the gene deletion and duplications of CYP2D6 Drug Metab. Rev. 2007 39 45 60 17364880
  14. [66]Lo YM Lun FM Chan KC Tsui NB Chong KC Lau TK Leung TY Zee BC Cantor CR Chiu RW Digital PCR for the molecular detection of fetal chromosomal aneuploidy Proc. Natl Acad. Sci. USA 2007 104 13116 13121 17664418 PMC1934923
  15. [67]Slamon DJ Clark GM Wong SG Levin WJ Ullrich A McGuire WL Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene Science 1987 235 177 182 3798106

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Authors
Qin, J., Jones, R. C., & Ramakrishnan, R.
Affiliations
Standard BioTools (United States) (US)
Corresponding author
Ramakrishnan, Ramesh
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2008-08-18
Volume
36
Issue
18
Pages
e116-e116
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkn518
PMC
PMC2566873
OpenAlex
W2108764754
Cited by
102
References
54
Citations by year
2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 8 · 2014: 9 · 2013: 10 · 2012: 17
FWCI
7.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Physical Sciences › Engineering › Biomedical Engineering › Nanopore and Nanochannel Transport Studies
Keywords
copy number variation, CYP2D6, ERBB2 amplification, breast cancer
MeSH terms
Autoantigens, Breast Neoplasms, Female, Humans, Genetic Variation, Gene Dosage, Genes, erbB-2, Cytochrome P-450 CYP2D6, Oligonucleotide Array Sequence Analysis, Nanotechnology, Ribonuclease P, Microfluidic Analytical Techniques

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