Disorders caused by chromosome abnormalities

Abstract

Many human genetic disorders result from unbalanced chromosome abnormalities, in which there is a net gain or loss of genetic material. Such imbalances often disrupt large numbers of dosage-sensitive, developmentally important genes and result in specific and complex phenotypes. Alternately, some chromosomal syndromes may be caused by a deletion or duplication of a single gene with pleiotropic effects. Traditionally, chromosome abnormalities were identified by visual inspection of the chromosomes under a microscope. The use of molecular cytogenetic technologies, such as fluorescence in situ hybridization and microarrays, has allowed for the identification of cryptic or submicroscopic imbalances, which are not visible under the light microscope. Microarrays have allowed for the identification of numerous new syndromes through a genotype-first approach in which patients with the same or overlapping genomic alterations are identified and then the phenotypes are described. Because many chromosomal alterations are large and encompass numerous genes, the ascertainment of individuals with overlapping deletions and varying clinical features may allow researchers to narrow the region in which to search for candidate genes.