Copy Number Variation and Human Health

Publisher Summary Development of high-resolution assays capable of detecting small segmental genetic alterations in a genome-wide fashion have led to the detection of widespread copy number variation (CNV) among the genomes of healthy individuals. This chapter identifies the extent of genetic variation in human populations and its impact on human health. CNVs are genomic gains and losses of 1 kb or larger, differentiating it from other forms of polymorphism and/or repeated DNAs in the human genome. This includes indels, microsatellites, minisatellites, simple repeats, telomeric and centromeric repetitive DNAs, and most interspersed repetitive elements. Since CNVs are considered subchromosomal imbalances, they are differentiated from whole chromosomal aneuploidies. CNVs are categorized into biallelic or multiallelic states. Biallelic CNVs have only two alleles and produce three different genotypes. CNVs with greater than two alleles are considered multiallelic and result in more than three different genotypes. Genomic imbalances, including CNVs, contribute to human diseases and are usually de novo in nature. Specific genomic imbalances are associated with as many as 50 genetic syndromes. Most of the remaining known genomic imbalances, considered benign CNVs because of their identification in healthy individuals, have more subtle consequences on human health.