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Single‐nucleotide polymorphism array coupled with multiple displacement amplification: Accuracy and spatial resolution for analysis of chromosome copy numbers in few cells
Author(s) -
Ling Jiawei,
Deng Yu,
Long Xiaolin,
Liu Jianqiao,
Du Hongzi,
Cao Baoqiang,
Xu Kangpu
Publication year - 2011
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1002/bab.64
Subject(s) - copy number variation , single nucleotide polymorphism , multiple displacement amplification , biology , snp array , snp , molecular inversion probe , genetics , microbiology and biotechnology , chromosome , gene duplication , copy number analysis , computational biology , polymerase chain reaction , gene , genome , dna extraction , genotype
When coupled with multiple displacement amplification (MDA), microarray‐based comparative genomic intensity allows detection of chromosome copy number aberrations even in single or few cells, but the actual performance of the system and their influencing factors have not been well defined. Here, using single‐nucleotide polymorphism (SNP) array, we analyzed copy number profiles from DNA amplified by MDA in 1–10 cells and estimated the accuracy and spatial resolution of the analysis. Based on the concordance of SNP copy numbers for DNA with and without MDA, the accuracy of the system can be significantly enhanced by using MDA‐amplified DNA as reference and also by increasing the cell numbers. Analyses under different smoothing treatments revealed a practical resolution of 2 Mb for 10 cells and 10 Mb for a single cell. When both cells with known chromosomal duplication and deletion were analyzed, this platform detected a copy number “loss” more accurately than a “gain” ( P < 0.01), particularly in single‐cell MDA products. Together, we demonstrated that SNP array coupled with MDA is reliable and efficient for detection of copy number aberrations in a small number of cells, and its accuracy and resolution can both be significantly enhanced with increasing the number of cells as MDA template.