Imperial College London
Alternate

Dr Peter Kelleher

Faculty of Medicine, Department of Infectious Disease

Reader in Immunology
 
 
 
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Contact

 

+44 (0)20 3315 8251p.kelleher

 
 
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Location

 

J.2.10Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Turro:2020:10.1038/s41586-020-2434-2,
author = {Turro, E and Astle, WJ and Megy, K and Graef, S and Greene, D and Shamardina, O and Allen, HL and Sanchis-Juan, A and Frontini, M and Thys, C and Stephens, J and Mapeta, R and Burren, OS and Downes, K and Haimel, M and Tuna, S and Deevi, SVV and Aitman, TJ and Bennett, DL and Calleja, P and Carss, K and Caulfield, MJ and Chinnery, PF and Dixon, PH and Gale, DP and James, R and Koziell, A and Laffan, MA and Levine, AP and Maher, ER and Markus, HS and Morales, J and Morrell, NW and Mumford, AD and Ormondroyd, E and Rankin, S and Rendon, A and Richardson, S and Roberts, I and Roy, NBA and Saleem, MA and Smith, KGC and Stark, H and Tan, RYY and Themistocleous, AC and Thrasher, AJ and Watkins, H and Webster, AR and Wilkins, MR and Williamson, C and Whitworth, J and Humphray, S and Bentley, DR and Kingston, N and Walker, N and Bradley, JR and Ashford, S and Penkett, CJ and Freson, K and Stirrups, KE and Raymond, FL and Ouwehand, WH},
doi = {10.1038/s41586-020-2434-2},
journal = {Nature},
pages = {96--102},
title = {Whole-genome sequencing of patients with rare diseases in a national health system},
url = {http://dx.doi.org/10.1038/s41586-020-2434-2},
volume = {583},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
AU  - Turro,E
AU  - Astle,WJ
AU  - Megy,K
AU  - Graef,S
AU  - Greene,D
AU  - Shamardina,O
AU  - Allen,HL
AU  - Sanchis-Juan,A
AU  - Frontini,M
AU  - Thys,C
AU  - Stephens,J
AU  - Mapeta,R
AU  - Burren,OS
AU  - Downes,K
AU  - Haimel,M
AU  - Tuna,S
AU  - Deevi,SVV
AU  - Aitman,TJ
AU  - Bennett,DL
AU  - Calleja,P
AU  - Carss,K
AU  - Caulfield,MJ
AU  - Chinnery,PF
AU  - Dixon,PH
AU  - Gale,DP
AU  - James,R
AU  - Koziell,A
AU  - Laffan,MA
AU  - Levine,AP
AU  - Maher,ER
AU  - Markus,HS
AU  - Morales,J
AU  - Morrell,NW
AU  - Mumford,AD
AU  - Ormondroyd,E
AU  - Rankin,S
AU  - Rendon,A
AU  - Richardson,S
AU  - Roberts,I
AU  - Roy,NBA
AU  - Saleem,MA
AU  - Smith,KGC
AU  - Stark,H
AU  - Tan,RYY
AU  - Themistocleous,AC
AU  - Thrasher,AJ
AU  - Watkins,H
AU  - Webster,AR
AU  - Wilkins,MR
AU  - Williamson,C
AU  - Whitworth,J
AU  - Humphray,S
AU  - Bentley,DR
AU  - Kingston,N
AU  - Walker,N
AU  - Bradley,JR
AU  - Ashford,S
AU  - Penkett,CJ
AU  - Freson,K
AU  - Stirrups,KE
AU  - Raymond,FL
AU  - Ouwehand,WH
DO  - 10.1038/s41586-020-2434-2
EP  - 102
PY  - 2020///
SN  - 0028-0836
SP  - 96
TI  - Whole-genome sequencing of patients with rare diseases in a national health system
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-020-2434-2
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000556405300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41586-020-2434-2
UR  - http://hdl.handle.net/10044/1/84701
VL  - 583
ER  -
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