التفاصيل البيبلوغرافية
العنوان:
Prevalence and architecture of de novo mutations in developmental disorders
المؤلفون:
McRae, JF , Clayton, S , Fitzgerald, TW , Kaplanis, J , Prigmore, E , Rajan, D , Sifrim, A , Aitken, S , Akawi, N , Alvi, M , Ambridge, K , Barrett, DM , Bayzetinova, T , Jones, P , Jones, WD , King, D , Krishnappa, N , Mason, LE , Singh, T , Tivey, AR , Ahmed, M , Anjum, U , Archer, H , Armstrong, R , Awada, J , Balasubramanian, M , Banka, S , Baralle, D , Barnicoat, A , Batstone, P , Baty, D , Bennett, C , Berg, J , Bernhard, B , Bevan, AP , Bitner-Glindzicz, M , Blair, E , Blyth, M , Bohanna, D , Bourdon, L , Bourn, D , Bradley, L , Brady, A , Brent, S , Brewer, C , Brunstrom, K , Bunyan, DJ , Burn, J , Canham, N , Castle, B , Chandler, K , Chatzimichali, E , Cilliers, D , Clarke, A , Clasper, S , Clayton-Smith, J , Clowes, V , Coates, A , Cole, T , Colgiu, I , Collins, A , Collinson, MN , Connell, F , Cooper, N , Cox, H , Cresswell, L , Cross, G , Crow, Y , D’Alessandro, M , Dabir, T , Davidson, R , Davies, S , de Vries, D , Dean, J , Deshpande, C , Devlin, G , Dixit, A , Dobbie, A , Donaldson, A , Donnai, D , Donnelly, D , Donnelly, C , Douglas, A , Douzgou, S , Duncan, A , Eason, J , Ellard, S , Ellis, I , Elmslie, F , Evans, K , Everest, S , Fendick, T , Fisher, R , Flinter, F , Foulds, N , Fry, A , Fryer, A , Gardiner, C , Gaunt, L , Ghali, N , Gibbons, R , Gill, H , Goodship, J , Goudie, D , Gray, E , Green, A , Greene, P , Greenhalgh, L , Gribble, S , Harrison, R , Harrison, L , Harrison, V , Hawkins, R , He, L , Hellens, S , Henderson, A , Hewitt, S , Hildyard, L , Hobson, E , Holden, S , Holder, M , Holder, S , Hollingsworth, G , Homfray, T , Humphreys, M , Hurst, J , Hutton, B , Ingram, S , Irving, M , Islam, L , Jackson, A , Jarvis, J , Jenkins, L , Johnson, D , Jones, E , Josifova, D , Joss, S , Kaemba, B , Kazembe, S , Kelsell, R , Kerr, B , Kingston, H , Kini, U , Kinning, E , Kirby, G , Kirk, C , Kivuva, E , Kraus, A , Kumar, D , Kumar, VKA , Lachlan, K , Lam, W , Lampe, A , Langman, C , Lees, M , Lim, D , Longman, C , Lowther, G , Lynch, SA , Magee, A , Maher, E , Male, A , Mansour, S , Marks, K , Martin, K , Maye, U , McCann, E , McConnell, V , McEntagart, M , McGowan, R , McKay, K , McKee, S , McMullan, DJ , McNerlan, S , McWilliam, C , Mehta, S , Metcalfe, K , Middleton, A , Miedzybrodzka, Z , Miles, E , Mohammed, S , Montgomery, T , Moore, D , Morgan, S , Morton, J , Mugalaasi, H , Murday, V , Murphy, H , Naik, S , Nemeth, A , Nevitt, L , Newbury-Ecob, R , Norman, A , O’Shea, R , Ogilvie, C , Ong, K-R , Park, S-M , Parker, MJ , Patel, C , Paterson, J , Payne, S , Perrett, D , Phipps, J , Pilz, DT , Pollard, M , Pottinger, C , Poulton, J , Pratt, N , Prescott, K , Price, S , Pridham, A , Procter, A , Purnell, H , Quarrell, O , Ragge, N , Rahbari, R , Randall, J , Rankin, J , Raymond, L , Rice, D , Robert, L , Roberts, E , Roberts, J , Roberts, P , Roberts, G , Ross, A , Rosser, E , Saggar, A , Samant, S , Sampson, J , Sandford, R , Sarkar, A , Schweiger, S , Scott, R , Scurr, I , Selby, A , Seller, A , Sequeira, C , Shannon, N , Sharif, S , Shaw-Smith, C , Shearing, E , Shears, D , Sheridan, E , Simonic, I , Singzon, R , Skitt, Z , Smith, A , Smith, K , Smithson, S , Sneddon, L , Splitt, M , Squires, M , Stewart, F , Stewart, H , Straub, V , Suri, M , Sutton, V , Swaminathan, GJ , Sweeney, E , Tatton-Brown, K , Taylor, C , Taylor, R , Tein, M , Temple, IK , Thomson, J , Tischkowitz, M , Tomkins, S , Torokwa, A , Treacy, B , Turner, C , Turnpenny, P , Tysoe, C , Vandersteen, A , Varghese, V , Vasudevan, P , Vijayarangakannan, P , Vogt, J , Wakeling, E , Wallwark, S , Waters, J , Weber, A , Wellesley, D , Whiteford, M , Widaa, S , Wilcox, S , Wilkinson, E , Williams, D , Williams, N , Wilson, L , Woods, G , Wragg, C , Wright, M , Yates, L , Yau, M , Nellåker, C , Parker, M , Firth, HV , Wright, CF , FitzPatrick, DR , Barrett, JC , Hurles, ME
المصدر:
2017, ' Prevalence and architecture of de novo mutations in developmental disorders ', Nature, vol. 542, no. 7642, pp. 433-438 . https://doi.org/10.1038/nature21062Test https://doi.org/10.1038/nature21062Test
بيانات النشر:
Nature, 2017.
سنة النشر:
2017
مصطلحات موضوعية:
Male , Parents , Heredity , Developmental Disabilities , GRIN2B , POGZ , Autoantigens , SMAD4 , CASK , GATAD2B , 0302 clinical medicine , TRIO , SMARCA2 , KCNH1 , Average Faces , CTNNB1 , SCN1A , Young adult , Casein Kinase II , Child , AUTS2 , MEF2C , Exome , ADNP , Exome sequencing , EP300 , KCNQ2 , KCNQ3 , EHMT1 , CNKSR2 , CREBBP , MYT1L , MED13L , CSNK2A1 , Protein Phosphatase 2C , PPP2R1A , ZBTB18 , CDKL5 , WAC , HNRNPU , Cohort , STXBP1 , Medical genetics , SYNGAP1 , Mi-2 Nucleosome Remodeling and Deacetylase Complex , Sex characteristics , AHDC1 , SCN8A , medicine.medical_specialty , SLC6A1 , FOXP1 , USP9X , Article , ANKRD11 , PUF60 , BRAF , 03 medical and health sciences , SATB2 , SMC1A , Intellectual Disability , BCL11A , GABRB3 , IQSEC2 , Humans , TBL1XR1 , TCF4 , MSL3 , TCF20 , DNM1 , EEF1A2 , SUV420H1 , DYRK1A , SETD5 , COL4A3BP , CTCF , CHD2 , R1 , CHD4 , 030104 developmental biology , NAA10 , HDAC8 , Mutation , KDM5B , CHAMP1 , PhenIcons , 030217 neurology & neurosurgery , Transcription Factors , 0301 basic medicine , ZMYND11 , PTEN , De novo mutation , Chromosomal Proteins, Non-Histone , PTPN11 , ASXL1 , Bioinformatics , medicine.disease_cause , ASXL3 , Cohort Studies , DEAD-box RNA Helicases , CHD8 , Prevalence , QRICH1 , KIF1A , Genetics , Sex Characteristics , GNAI1 , Multidisciplinary , WDR45 , Middle Aged , KMT2A , PPM1D , MECP2 , DNA-Binding Proteins , PPP2R5D , Phenotype , PACS1 , ras GTPase-Activating Proteins , DDX3X , Female , FOXG1 , SET , Myeloid-Lymphoid Leukemia Protein , Developmental Disease , Adult , KANSL1 , Adolescent , NFIX , Nerve Tissue Proteins , PURA , Biology , KAT6B , KAT6A , NSD1 , PDHA1 , ALG13 , Young Adult , Seizures , CDC2 Protein Kinase , medicine , Journal Article , QH426 , Homeodomain Proteins , ITPR1 , DYNC1H1 , GNAO1 , Histone-Lysine N-Methyltransferase , Sequence Analysis, DNA , ZC4H2 , ARID1B , Repressor Proteins , CNOT3 , SCN2A , SLC35A2 , CDK13
الوصف:
Children with severe, undiagnosed developmental disorders (DDs) are enriched for damaging de novo mutations (DNMs) in developmentally important genes. We exome sequenced 4,294 families with children with DDs, and meta-analysed these data with published data on 3,287 children with similar disorders. We show that the most significant factors influencing the diagnostic yield of de novo mutations are the sex of the child, the relatedness of their parents and the age of both father and mother. We identified 95 genes enriched for damaging de novo mutation at genome-wide significance (P < 5 x 10-7), including fourteen genes for which compelling data for causation was previously lacking. The large number of genome-wide significant findings allow us to demonstrate that, at current cost differentials, exome sequencing has much greater power than genome sequencing for novel gene discovery in genetically heterogeneous disorders. We estimate that 42.5% of our cohort likely carry pathogenic de novo single nucleotide variants (SNVs) and indels in coding sequences, with approximately half operating by a loss-of-function mechanism, and the remainder being gain-of-function. We established that most haploinsufficient developmental disorders have already been identified, but that many gain-of-function disorders remain to be discovered. Extrapolating from the DDD cohort to the general population, we estimate that de novo dominant developmental disorders have an average birth prevalence of 1 in 168 to 1 in 377, depending on parental age.
وصف الملف:
application/pdf; text; application/vnd.openxmlformats-officedocument.wordprocessingml.document
اللغة:
English
تدمد:
0028-0836
الوصول الحر:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac7e5d7fcf4831a7f999caac0003a6dfTest
حقوق:
OPEN
رقم الانضمام:
edsair.doi.dedup.....ac7e5d7fcf4831a7f999caac0003a6df
قاعدة البيانات:
OpenAIRE
