Delineation of New Disorders and Phenotypic Expansion of Known Disorders Through Whole Exome Sequencing

Abstract Whole-exome sequencing (WES) has revolutionized gene discovery in human disease, drastically improving detection of pathogenic variation, expanding the delineation of molecular networks, enriching characterization of genomic architecture and refining the genotype–endophenotype distinctions in heterogeneous phenotypes. WES studies, often aided by collaborative consortia, have proven particularly effective in identifying the genetic etiology of autism, epilepsy, neurodevelopmental disabilities, brain malformations, congenital heart disease, congenital diaphragmatic hernia, multiple congenital anomalies, rare diseases, and the extreme phenotypes of common diseases. Analysis of proband and parents with a trio design has proven effective in the identification of de novo events and their contribution to disease, extending analysis of sporadic conditions beyond prior studies using comparative genomic hybridization and chromosome microarrays. WES has demonstrable utility in the clinical setting with impactful diagnostic yield across many diseases and is increasingly being adopted for its unbiased, efficient, and accurate ability to investigate the basis of human disease.
Source: Current Genetic Medicine Reports - Category: Genetics & Stem Cells Source Type: research