小柯机器人

科学家利用全基因组测序发现多种罕见疾病
2020-06-28 14:48

英国剑桥大学Willem H. Ouwehand、F. Lucy Raymond、Ernest Turro等研究人员利用全基因组测序对罕见疾病进行了挖掘。这一研究成果于2020年6月24日在线发表在《自然》上。

研究人员使用了全基因组测序(WGS)来简化诊断并在基因组的编码和非编码区域发现未知的病因变异。研究人员为13037名参与者生成了WGS数据,其中9802名患有罕见疾病,并为7065个广泛表型参与者中的1138名提供了基因诊断。研究人员确定了基因与稀有疾病之间的95个孟德尔关联,自2015年以来已发现11个,而至少79个被确认是病因。
 
通过生成英国生物银行参与者的WGS数据,研究人员发现稀有的等位基因可以解释某些个体中红细胞的异常。最后,研究人员鉴定了四种新的非编码变异,它们通过破坏ARPC1B、GATA1、LRBA和MPL的转录而引起疾病。这项研究证明了在常规医疗中使用WGS进行诊断与病因发现的协同作用。
 
据悉,大多数患有罕见疾病的患者没有接受分子诊断,并且有一半以上此类疾病的病因学变异和致病基因仍有待发现。
 
附:英文原文

Title: Whole-genome sequencing of patients with rare diseases in a national health system

Author: Ernest Turro, William J. Astle, Karyn Megy, Stefan Grf, Daniel Greene, Olga Shamardina, Hana Lango Allen, Alba Sanchis-Juan, Mattia Frontini, Chantal Thys, Jonathan Stephens, Rutendo Mapeta, Oliver S. Burren, Kate Downes, Matthias Haimel, Salih Tuna, Sri V. V. Deevi, Timothy J. Aitman, David L. Bennett, Paul Calleja, Keren Carss, Mark J. Caulfield, Patrick F. Chinnery, Peter H. Dixon, Daniel P. Gale, Roger James, Ania Koziell, Michael A. Laffan, Adam P. Levine, Eamonn R. Maher, Hugh S. Markus, Joannella Morales, Nicholas W. Morrell, Andrew D. Mumford, Elizabeth Ormondroyd, Stuart Rankin, Augusto Rendon, Sylvia Richardson, Irene Roberts, Noemi B. A. Roy, Moin A. Saleem, Kenneth G. C. Smith, Hannah Stark, Rhea Y. Y. Tan, Andreas C. Themistocleous, Adrian J. Thrasher, Hugh Watkins, Andrew R. Webster, Martin R. Wilkins, Catherine Williamson, James Whitworth

Issue&Volume: 2020-06-24

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.

DOI: 10.1038/s41586-020-2434-2

Source: https://www.nature.com/articles/s41586-020-2434-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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