title: DECIPHER: web-based, community resource for clinical interpretation of rare variants in developmental disorders.
abstract: Patients with developmental disorders often harbour sub-microscopic deletions or duplications that lead to a disruption of normal gene expression or perturbation in the copy number of dosage-sensitive genes. Clinical interpretation for such patients in isolation is hindered by the rarity and novelty of such disorders. The DECIPHER project (https://decipher.sanger.ac.uk) was established in 2004 as an accessible online repository of genomic and associated phenotypic data with the primary goal of aiding the clinical interpretation of rare copy-number variants (CNVs). DECIPHER integrates information from a variety of bioinformatics resources and uses visualization tools to identify potential disease genes within a CNV. A two-tier access system permits clinicians and clinical scientists to maintain confidential linked anonymous records of phenotypes and CNVs for their patients that, with informed consent, can subsequently be shared with the wider clinical genetics and research communities. Advances in next-generation sequencing technologies are making it practical and affordable to sequence the whole exome/genome of patients who display features suggestive of a genetic disorder. This approach enables the identification of smaller intragenic mutations including single-nucleotide variants that are not accessible even with high-resolution genomic array analysis. This article briefly summarizes the current status and achievements of the DECIPHER project and looks ahead to the opportunities and challenges of jointly analysing structural and sequence variation in the human genome.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Ganesh J
authors.initials: GJ
authors.lastname: Swaminathan
authors.forename: Eugene
authors.initials: E
authors.lastname: Bragin
authors.forename: Eleni A
authors.initials: EA
authors.lastname: Chatzimichali
authors.forename: Manuel
authors.initials: M
authors.lastname: Corpas
authors.forename: A Paul
authors.initials: AP
authors.lastname: Bevan
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Wright
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Helen V
authors.initials: HV
authors.lastname: Firth
mesh_terms: D019295:Computational Biology; D056915:DNA Copy Number Variations; D030561:Databases, Nucleic Acid; D002658:Developmental Disabilities / Q000235:genetics*; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D033181:Information Dissemination; D020407:Internet; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide