dc.contributor.author | Gallone, G | |
dc.contributor.author | Bruntraeger, M | |
dc.contributor.author | McRae, JF | |
dc.contributor.author | Prigmore, E | |
dc.contributor.author | Short, P | |
dc.contributor.author | Niemi, M | |
dc.contributor.author | Kaplanis, J | |
dc.contributor.author | Radford, EJ | |
dc.contributor.author | Akawi, N | |
dc.contributor.author | Balasubramanian, M | |
dc.contributor.author | Dean, J | |
dc.contributor.author | Horton, R | |
dc.contributor.author | Hulbert, A | |
dc.contributor.author | Johnson, DS | |
dc.contributor.author | Johnson, K | |
dc.contributor.author | Kumar, D | |
dc.contributor.author | Lynch, SA | |
dc.contributor.author | Mehta, SG | |
dc.contributor.author | Morton, J | |
dc.contributor.author | Parker, MJ | |
dc.contributor.author | Splitt, M | |
dc.contributor.author | Turnpenny, PD | |
dc.contributor.author | Vasudevan, PC | |
dc.contributor.author | Wright, M | |
dc.contributor.author | Bassett, A | |
dc.contributor.author | Gerety, SS | |
dc.contributor.author | Wright, CF | |
dc.contributor.author | FitzPatrick, DR | |
dc.contributor.author | Firth, HV | |
dc.contributor.author | Hurles, ME | |
dc.contributor.author | Barrett, JC | |
dc.date.accessioned | 2019-01-30T16:06:30Z | |
dc.date.issued | 2018-12-07 | |
dc.description.abstract | 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. | en_GB |
dc.description.sponsorship | Health Innovation Challenge Fund | en_GB |
dc.description.sponsorship | St John’s College, Cambridge | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.identifier.citation | Vol. 362, pp. 1161 - 1164 | en_GB |
dc.identifier.doi | 10.1126/science.aar6731 | |
dc.identifier.grantnumber | HICF-1009-003 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/35672 | |
dc.language.iso | en | en_GB |
dc.publisher | American Association for the Advancement of Science | en_GB |
dc.rights | © 2017 The Authors, some rights reserved. | en_GB |
dc.title | Quantifying the contribution of recessive coding variation to developmental disorders | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-01-30T16:06:30Z | |
dc.identifier.issn | 0036-8075 | |
dc.description | This is the author accepted manuscript. The final version is available from AAAS via the DOI in this record | en_GB |
dc.identifier.journal | Science | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2018-10-29 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2018-12-07 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.technicalException | technicalFailure | |
refterms.technicalExceptionExplanation | Deposits for the Institute of Medical Education were not being sent to the general review taskpool but to the taskpool of an individual who at the time was not reviewing deposits. We were therefore unaware of the issue until alerted by Atmire (repository developer) on 30/1/19. At this point we rectified the issue. | |
refterms.dateFCD | 2019-01-30T16:02:50Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-01-30T16:06:32Z | |
refterms.panel | A | en_GB |