Recent advances in array comparative genomic hybridization technologies and their applications in human genetics

Abstract

Array comparative genomic hybridization (array CGH) is a method used to detect segmental DNA copy number alterations. Recently, advances in this technology have enabled high-resolution examination for identifying genetic alterations and copy number variations on a genome-wide scale. This review describes the current genomic array platforms and CGH methodologies, highlights their applications for studying cancer genetics, constitutional disease and human variation, and discusses visualization and analytical software programs for computational interpretation of array CGH data.

A genomic analysis of adult T-cell leukemia

“…Comparative genomic hybridization (CGH) has thus revealed recurrent gains in chromosomes 2p, 3p, 7q and 14q as well as losses in 6q in ATL cells (Ariyama et al, 1999;Tsukasaki et al, 2001). However, CGH or its successor, bacterial artificial chromosome (BAC) arraybased CGH, is able to analyse chromosome copy number alterations (CNAs) at a resolution of only several hundred kilobase pairs (Lockwood et al, 2005). High-density oligonucleotide microarrays originally designed for genotyping of single nucleotide polymorphisms (SNPs) have recently been adapted for CNA analysis (Lin et al, 2004;Nannya et al, 2005).…”

Analysis of chromosome copy number in leukemic cells by different microarray platforms

“…1 In these studies, most of these mutations were heterozygous mutation and homozygous mutation was only detected in 30% of patients with JAK2 mutation using DNA samples. 2 Thus, the prevalence of the expression of JAK2 V617F in myeloid malignancies remains unclear.…”

“…1 Such CNAs range in size from an entire chromosome to several kilobase pairs, with many of the smaller changes being undetectable by conventional bacterial artificial chromosome-based comparative genomic hybridization (CGH), which has a resolution of several hundred kilobase pairs. 2 This limitation has recently been overcome by the adaptation of high-density oligonucleotide microarrays that were originally developed for typing of single nucleotide polymorphisms (SNPs) to the evaluation of CNAs. 3 Sophisticated software for such analysis, including dChip (http://biosun1.harvard.edu/complab/dchip) and CNAG (http://www.genome.umin.jp/CNAG.html), is now available online.…”

Getting it right: designing microarray (and not ‘microawry') comparative genomic hybridization studies for cancer research

“…3,10,12 BAC probes vary in length from 100 to 200 kb and the resolution (ie the distance between each DNA target represented on the array) of each BAC array is defined by the number of unique probes it contains. The probe content of genome-wide BAC arrays range from 2400 to B32 000 unique elements (tiling path array).…”

“…11 Hence, numerous methodological issues need to be addressed before its impact on translational research can be fully realized. Although there have been several excellent reviews 10,12,13 on the current status of this technology, there is currently very little guidance available regarding the appropriate design of experiments incorporating aCGH, and how best to integrate the results obtained from aCGH with other 'omic' technologies including gene-expression arrays. The 'omic' field is plagued with acronyms and jargons, some of which are summarized in Table 1.…”