ArrayCGH

ArrayCGH, or array comparative genomic hybridization, is a molecular cytogenetic technique for genome-wide detection of copy number variations (CNVs) by comparing a test DNA sample to a reference. It uses microarray slides with thousands of DNA probes spanning the genome.

Test and reference DNAs are labeled with different fluorescent dyes and co-hybridized to the array. After hybridization and washing, the slide is scanned to measure fluorescence intensities at each probe; the log2 ratio of test to reference signal reflects copy number. Segmentation algorithms identify regions of consistent copy number, producing a genome-wide map of gains and losses.

Variants detected include deletions and duplications ordered by size; resolution depends on array design: BAC arrays offer lower resolution, oligonucleotide arrays provide higher resolution (tens of kilobases to kilobases). Array CGH detects copy-number changes but not balanced rearrangements or copy-neutral events; to detect copy-neutral events, SNP arrays or sequencing are needed.

Applications include clinical genetics for developmental delay, intellectual disability, and multiple congenital anomalies; cancer genomics for profiling tumor copy-number landscapes; and research into CNVs, genome structure, and evolutionary studies.

Limitations encompass the inability to detect balanced rearrangements; mosaicism may be underestimated; DNA quality and tumor purity affect results; array design bias and repeat-rich regions may affect accuracy. Data interpretation often requires matched normal controls for somatic analyses and careful consideration of clinical context.

History: Conceptual roots lie in comparative genomic hybridization developed in the 1990s, evolving from metaphase-CGH to high-resolution array-based methods. Early demonstrations established the method's utility in both cancer and developmental disorders, leading to widespread clinical and research use.