Chapter 11 - Clinical Applications of Whole-Genome Chromosomal Microarray Analysis

Abstract

Copy number variants (CNVs) are a class of mutations involving the loss or gain of genomic material, defined here as >1 kb in size but below the level of detection by conventional cytogenetic banding techniques (~5–10 Mb). Whole-genome CNV analysis, referred to here as chromosomal microarray analysis (CMA), has been optimized for clinical use by incorporating design elements that maximize the ability to detect potentially pathogenic CNVs while minimizing the detection of known benign CNVs. This technology has recently been implemented as a routine clinical diagnostic test in the evaluation of individuals with unexplained developmental delay, intellectual disability, autism spectrum disorders, and/or congenital anomalies. The lessons learned through the development and implementation of CMA for clinical testing can be used to guide the development and transition of other genome-wide analysis methods, such as whole-genome sequencing, into the clinical setting.