title: Genotype to phenotype-discovery and characterization of novel genomic disorders in a "genotype-first" era.
abstract: Recent advances in technology for detecting copy number changes have enabled genome-wide detection of submicroscopic deletions and duplications. As these technologies are applied to large cohorts of patients with diverse phenotypes, novel genomic disorders are defined by a common genotype (deletion or duplication) rather than a common phenotype. The discovery of new genomic disorders using this "genotype-first" approach has increased dramatically, and several recently described recurrent rearrangements are associated with a surprisingly wide range of phenotypes. This review will discuss the importance of genomic architecture for generating recurrent rearrangements, implications of the genotype-first approach for medical genetics, and features of several new genomic disorders with highly variable phenotypes.
authors.affiliation: Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, USA. hmefford@u.washington.edu
authors.forename: Heather C
authors.initials: HC
authors.lastname: Mefford
mesh_terms: D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D020440:Gene Duplication; D015321:Gene Rearrangement; D015894:Genome, Human / Q000235:genetics*; D023281:Genomics / Q000379:methods* / Q000639:trends; D005838:Genotype; D006801:Humans; D010641:Phenotype