title: Interpretation of genetic variants.
abstract: Sequencing of the human genome and introduction of clinical next-generation sequencing enable discovery of all DNA variants carried by an individual. Variants may be solely responsible for disease, may contribute to disease, or may have no influence on the development of disease. Interpreting the effect of these variants upon disease is a major challenge for medicine. Although the process is still evolving, certain methods are useful in discriminating the effect of variants upon phenotype. These methods have been employed to the greatest extent in Mendelian disorders where deleterious changes in one gene can cause disease. Here, we briefly review the relative merits of these methods, with emphasis on using a comprehensive approach modelled after the analysis of variants that causes cystic fibrosis.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Sosnay
authors.forename: Garry R
authors.initials: GR
authors.lastname: Cutting
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Genetic Variation; Genotype; Mutation Analysis; Phenotype; Population Genetics