CNVs have also been identified as one of the most common causes of human disease. In fact, one of the earliest and most significant clinical benefits of the Human Genome Project has been the application of whole-genome CNV analysis to evaluate individuals with developmental disabilities, including developmental delay, intellectual disability, autism, epilepsy, and/or birth defects, a group of disorders representing up to 14% of the population 4. Commonly referred to as cytogenetic or chromosomal microarrays (CMA), these technologies have quickly replaced the standard G-banded karyotype as the first-tier genetic test for the evaluation of this patient population.5,6 There are many technology platforms available for whole-genome copy number analysis at resolutions of 100–500 kb (compared to ~5–10 Mb for karyotype), with even higher resolution at “clinical targets,” such as individual genes in which haploinsufficiency leads to dominant Mendelian disorders. From numerous published studies, the yield of clinically significant or pathogenic CNVs by CMA is 15–20%, compared with a yield of ~3–5% by standard cytogenetic analysis in the same patient population.5
