EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001001386EGAEGA study EGAS00001001386WGS of 8 trios - affected child and both normal parentsEGArestrictedIntellectual Development Disorders, Mental, Intellectual Development Disorder, Retardation, Materials, Mental Retardation, Disorders, Genetic, Disabilities, determination, Mental Deficiencies, MENTAL DEFIC, Disability, Intellectual Disabilities, Deficiencies, Low intelligence, Poor school performance, Dull intelligence, Idiocy, chemical analysis., Gene, Intellectual, whole genome, Cistrons, Development Disorders, Intellectual Disability, primary structure of sequence macromolecule, Psychosocial Mental, Psychosocial, Psychosocial Mental Retardations, Deficiency, Mental Deficiency, Psychosocial Mental Retardation, Material, Disorder, Psychosocial intellectual disability, Development Disorder, sequence, Genetic Materials, Cistron, DEFIC MENTAL, assay, Retardations, Mental Retardations, Intellectual Development, Genetic Material, intellectual disabilityTRIO, Disorders, Ardi1b, Materials, determination, AI836955, M89, Intellectual Disabilities, Poor school performance, composed of, ELD|OSA1, Status, OSIL, Cchb3, diseases, B230217J03Rik, diseases and disorders, synganglion, l(3)S138606, l(3)S036810, IFS2, average, Retardation, human disease, Upf1p, Disabilities, Genomes, upf1, Dull intelligence, composition, Intellectual, suprasegmental levels of nervous system, CG18214, Trio, l(3)S[1386/06], l(3)S[1372/3], 0959/14, Homo sapiens disease, Retardations, STAP, Nucleotide, CG1559, Intellectual Development Disorder, suprasegmental structures, wide/broad, cHILD, pediatric interstitial lung disease, DAN15, OSF-6, ATUPF1, Step Parents, Genome Sequencing, CACNLB3, Validation Studies, Stepparent, Development Disorders, DmUpf1, UPF1, Psychosocial Mental Retardations, Parenthood, 8030481M12, p62B, Complete Genome, Step-Parents, Genetic Materials, RENT1, Genetic Material, nucleotides, child, Intellectual Development Disorders, Parent, ILD specific to childhood, DmelCG1559, content, Encephalon, Parental Age, l(3)036810, Disability, OSA2, HUPF1, Exomes, Parental Ages, common, BFLS, whole genome, Children, Age, l(3)S095914, Dm-Upf1, disease, 1372/03, wide, Osi, Patient, Material, Psychosocial intellectual disability, Development Disorder, microarray, Cistron, mKIAA1235, A170, Mental Retardations, Intellectual Development, CACH3B, the brain, ZIP, PDB3, Mental, other disease, Ca(v)beta3, MQD22.15, HH17, young adult, MENTAL DEFIC, Deficiencies, CAB3, 9330189K18Rik, number, CG9208, Gene, CMA, MQD22_15, broad, presence, pNORF1, WGS., p60, 0368/10, CHILD, p62, Upflp, disease or disorder, CASA, Parenthood Status, smg-2, interstitial lung disease of childhood, Stepparents, intellectual disability, study, ARHGEF23, Complete, Mental Retardation, Whole Genome, BEST:LD36950, Genetic, mKIAA1823, Rent1, SUP113, Low intelligence, Complete Genome Sequencing, STONE14, l(3)S137203, CENP-31, BORJ, paediatric interstitial lung disease, Sequencing, chILD, non-neoplastic, juvenile stage, DmelCG18214, 6A3-5, Ages, Clients, NORF1, Disorder, childhood interstitial lung disease, Whole, DTrio, disorder, 2700007B13Rik, ZIP3, WGS, B430202H16Rik, lumen, ELD/OSA1, P250R, Mental Deficiencies, space, Parental, disorders, Idiocy, 1386/06, medical condition, compositionality, Cistrons, Client, encephalon, UNC-73/Trio, Psychosocial Mental, count in organism, Psychosocial Mental Retardation, chemical analysis, sequence, condition, Step-Parent, LOW-LEVEL BETA-AMYLASE 1, anatomical spaces, BRIGHT, l(3)trio, MRD12, BAF250B, lumen space, tgat, chILD syndrome, 4931428F02Rik, Intellectual Disability, primary structure of sequence macromolecule, Psychosocial, PNORF-1, Deficiency, Mental Deficiency, children's interstitial lung disease, structure, cardinality, l(3)6D104, Beta3, DEFIC MENTAL, MOF4, assayfalseNovel genes for Intellectual Disability identified using whole genome sequence and pathway analysisIntellectual Disability (ID) is one of the most common global disorders. However for ~30% of patients with ID no cause is identified, despite a clinical diagnostic odyssey that includes genome wide clinical microarray (CMA). We carefully selected 8 trios, each composed of a child with ID and brain structural defect, and both normal parents for whole genome sequencing (WGS). We conducted WGS on the trio and filtered out de novo single nucleotide variants (SNVs) and then used a pathway-based refinement to select candidates. We confirmed a de novo pathogenic SNV in ARID1B, and likely pathogenic SNVs in CACNB3, SPRY4, PHF6, SQSTM1 and UPF1 in 5 of the 8 children. All genes except ARID1B and PHF6 are previously unreported for ID. We analysed our WGS data using 4 independent algorthims for copy number and structural variation including using de novo whole genome assembly. We confirmed one likely contributory 165kb de novo CNV (missed by CMA). We conducted a validation study of over 2000 exomes for our novel candidate genes and also present a strategy to analyze the non-coding sequence space. This study provides an extensive analysis of WGS in the context of ID and yielded causative variants in >60% of cases.2017-07-26 15:39:29EGAS000010013869606EGAD00001001467EGAC00000000011