title: Single-nucleotide polymorphism array coupled with multiple displacement amplification: accuracy and spatial resolution for analysis of chromosome copy numbers in few cells.
abstract: 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.
authors.affiliation: Center for Reproductive Medicine, Guangzhou Institute of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Ling
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Long
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Liu
authors.forename: Hongzi
authors.initials: H
authors.lastname: Du
authors.forename: Baoqiang
authors.initials: B
authors.lastname: Cao
authors.forename: Kangpu
authors.initials: K
authors.lastname: Xu
mesh_terms: D002460:Cell Line; D002869:Chromosome Aberrations; D058674:Chromosome Duplication / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000473:pathology*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*