Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aar6731 |
Quantifying the contribution of recessive coding variation to developmental disorders | |
Martin, Hilary C.1; Jones, Wendy D.1,2; McIntyre, Rebecca1; Sanchez-Andrade, Gabriela1; Sanderson, Mark1; Stephenson, James D.1,3; Jones, Carla P.1; Handsaker, Juliet1; Gallone, Giuseppe1; Bruntraeger, Michaela1; McRae, Jeremy F.1; Prigmore, Elena1; Short, Patrick1; Niemi, Mari1; Kaplanis, Joanna1; Radford, Elizabeth J.1,4; Akavvi, Nadia5; Balasubramanian, Meena6; Dean, John7; Horton, Rachel8; Hulbert, Alice9; Johnson, Diana S.6; Johnson, Katie10; Kumar, Dhavendra11; Lynch, Sally Ann12; Mehta, Sarju G.13; Morton, Jenny14; Parker, Michael J.15; Splitt, Miranda16; Turnpenny, Peter D.17; Vasudevan, Pradeep C.18; Wright, Michael16; Bassett, Andrew1; Gerety, Sebastian S.1; Wright, Caroline F.19; FitzPatrick, David R.20; Firth, Helen, V1,13; Hurles, Matthew E.1; Barrett, Jeffrey C.1 | |
2018-12-07 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6419页码:1161-+ |
文章类型 | Article |
语种 | 英语 |
国家 | England; Scotland; Wales; Ireland |
英文摘要 | We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, owing to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000452506300058 |
WOS关键词 | DE-NOVO MUTATIONS ; INTELLECTUAL DISABILITY ; GENETIC-VARIATION ; NALCN CAUSE ; SPECTRUM ; PREVALENCE ; HYPOTONIA ; ALIGNMENT ; VARIANTS ; GENOTYPE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200249 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England; 2.Natl Hlth Serv NHS Fdn Trust, Great Ormond St Hosp Children, Great Ormond St Hosp, Great Ormond St, London WC1N 3JH, England; 3.European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Hinxton CB10 1SD, Cambs, England; 4.Campridge Univ Hosp NHS Fdn Trust, Dept Paediat, Cambridge, England; 5.Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England; 6.Sheffield Childrens NHS Fdn Trust, Sheffield Clin Genet Serv, OPD2, Northern Gen Hosp, Herries Rd, Sheffield S5 7AU, S Yorkshire, England; 7.Aberdeen Royal Infirm, Dept Genet, Aberdeen, Scotland; 8.Princess Anne Hosp, Wessex Clin Genet Serv, G Level,Coxford Rd, Southampton SO16 5YA, Hants, England; 9.Liverpool Womens NHS Fdn Trust, Cheshlre & Merseyside Clin Genet Serv, Crown St, Liverpool L8 7SS, Merseyside, England; 10.Dept Clin Genet, City Hosp Campus,Hucknall Rd, Nottingham NG5 1PB, England; 11.Univ Hosp Wales, Inst Canc & Genet, Cardiff, S Glam, Wales; 12.Temple St Childrens Hosp, Dublin, Ireland; 13.Cambridge Univ Hosp NHS Fdn Trust, Dept Clin Genet, Cambridge, England; 14.Birmingham Womens Hosp, Clin Genet Unit, Birmingham B15 2TG, W Midlands, England; 15.Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Western Bank, Sheffield S10 2TH, S Yorkshire, England; 16.Newcastle Upon Tyne Hosp NHS Fdn Trust, Northern Genet Serv, Newcastle Upon Tyne, Tyne & Wear, England; 17.Royal Devon & Exeter NHS Fdn Trust, Clin Genet, Exeter, Devon, England; 18.Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Dept Clin Genet, Leicester LE1 5WW, Leics, England; 19.Univ Exeter, RILD, Inst Biomed & Clin Sci, Med Sch,Royal Devon & Exeter Hosp, Barrack Rd, Exeter EX2 5DH, Devon, England; 20.Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC,Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland |
推荐引用方式 GB/T 7714 | Martin, Hilary C.,Jones, Wendy D.,McIntyre, Rebecca,et al. Quantifying the contribution of recessive coding variation to developmental disorders[J]. SCIENCE,2018,362(6419):1161-+. |
APA | Martin, Hilary C..,Jones, Wendy D..,McIntyre, Rebecca.,Sanchez-Andrade, Gabriela.,Sanderson, Mark.,...&Barrett, Jeffrey C..(2018).Quantifying the contribution of recessive coding variation to developmental disorders.SCIENCE,362(6419),1161-+. |
MLA | Martin, Hilary C.,et al."Quantifying the contribution of recessive coding variation to developmental disorders".SCIENCE 362.6419(2018):1161-+. |
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