@article{4e8403ff93cb4518b826e688149a0828,
title = "Whole-genome sequencing of patients with rare diseases in a national health system",
abstract = "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.",
author = "{NIHR BioResource for the 100,000 Genomes Project} and Ernest Turro and Astle, {William J.} and Karyn Megy and Stefan Gr{\"a}f and Daniel Greene and Olga Shamardina and Allen, {Hana Lango} and Alba Sanchis-Juan and Mattia Frontini and Chantal Thys and Jonathan Stephens and Rutendo Mapeta and Burren, {Oliver S.} and Kate Downes and Matthias Haimel and Salih Tuna and Deevi, {Sri V.V.} and Aitman, {Timothy J.} and Bennett, {David L.} and Paul Calleja and Keren Carss and Caulfield, {Mark J.} and Chinnery, {Patrick F.} and Dixon, {Peter H.} and Gale, {Daniel P.} and Roger James and Ania Koziell and Laffan, {Michael A.} and Levine, {Adam P.} and Maher, {Eamonn R.} and Markus, {Hugh S.} and Joannella Morales and Morrell, {Nicholas W.} and Mumford, {Andrew D.} and Elizabeth Ormondroyd and Stuart Rankin and Augusto Rendon and Sylvia Richardson and Irene Roberts and Roy, {Noemi B.A.} and Saleem, {Moin A.} and Smith, {Kenneth G.C.} and Hannah Stark and Tan, {Rhea Y.Y.} and Themistocleous, {Andreas C.} and Thrasher, {Adrian J.} and Hugh Watkins and Gharavi, {Ali G.} and Daniel Greene and Ernest Turro",
note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2020",
month = jul,
day = "2",
doi = "10.1038/s41586-020-2434-2",
language = "English",
volume = "583",
pages = "96--102",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7814",
}