GSTDTAP  > 地球科学
DOI10.1126/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
ISSN0036-8075
EISSN1095-9203
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
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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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