Counting Chromosomes to Exons: Advances in Copy Number Detection

Abstract

Abnormal copy number of chromosomes, genes, or individual exons can have deleterious effects that lead to recognizable genetic disorders. Until recently, the traditional methods of karyotyping, fluorescence in situ hybridization, and rudimentary PCR-based assays were the only choices available to detect copy number abnormalities. The advent of chromosomal microarrays and next-generation sequencing has now dramatically improved our ability to detect deletions or duplications with superior resolution compared to that possible with previous methods. Each method has inherent properties and variations that provide advantages in detecting mutations in specific genomic environments, but those same properties can be limiting in other regions as well as in scalability. Improvements in bioinformatics algorithms predict a complete shift toward next-generation sequencing for detecting the entire range of copy number abnormalities, although microarray and other technologies will continue to be useful as confirmatory tests and for investigating complex structural rearrangements and non-unique sequences.