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研究报告28种遗传疾病证据
2020-10-15 16:12

美国威康桑格研究所Kyle Retterer研究组在研究中取得进展。他们列出了结合医疗保健和研究数据发现的28种遗传疾病的证据。这一研究成果于2020年10月14日发表在国际顶尖学术期刊《自然》上。

为了鉴定以前未描述的与发育障碍相关的基因,他们整合了来自31,058名发育障碍个体的父母-后代的医疗保健和研究外显子序列数据,并开发了基于模拟的统计测试以鉴定从头合成基因特异性富集突变。他们鉴定出与发育障碍显著相关的285个基因,包括28个以前与发育障碍没有显著相关的基因。尽管他们检测到更多与发育障碍相关的基因,但仍无法解释蛋白质编码基因中大量的从头突变。

模型表明尚未描述与发育障碍相关的1,000多个基因,其中许多基因可能比目前已知的基因具有较低的渗透性。对临床诊断数据集的研究访问对于完成与发育性疾病相关的基因图谱至关重要。

据介绍,蛋白质编码基因的从头突变是发育障碍的公认原因。然而,已知与发育障碍有关的基因仅占这种从头突变的一小部分被观察到。

附:英文原文

Title: Evidence for 28 genetic disorders discovered by combining healthcare and research data

Author: Joanna Kaplanis, Kaitlin E. Samocha, Laurens Wiel, Zhancheng Zhang, Kevin J. Arvai, Ruth Y. Eberhardt, Giuseppe Gallone, Stefan H. Lelieveld, Hilary C. Martin, Jeremy F. McRae, Patrick J. Short, Rebecca I. Torene, Elke de Boer, Petr Danecek, Eugene J. Gardner, Ni Huang, Jenny Lord, Iigo Martincorena, Rolph Pfundt, Margot R. F. Reijnders, Alison Yeung, Helger G. Yntema, Lisenka E. L. M. Vissers, Jane Juusola, Caroline F. Wright, Han G. Brunner, Helen V. Firth, David R. FitzPatrick, Jeffrey C. Barrett, Matthew E. Hurles, Christian Gilissen, Kyle Retterer

Issue&Volume: 2020-10-14

Abstract: De novo mutations in protein-coding genes are a well-established cause of developmental disorders1. However, genes known to be associated with developmental disorders account for only a minority of the observed excess of such de novo mutations1,2. Here, to identify previously undescribed genes associated with developmental disorders, we integrate healthcare and research exome-sequence data from 31,058 parent–offspring trios of individuals with developmental disorders, and develop a simulation-based statistical test to identify gene-specific enrichment of de novo mutations. We identified 285 genes that were significantly associated with developmental disorders, including 28 that had not previously been robustly associated with developmental disorders. Although we detected more genes associated with developmental disorders, much of the excess of de novo mutations in protein-coding genes remains unaccounted for. Modelling suggests that more than 1,000 genes associated with developmental disorders have not yet been described, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of genes associated with developmental disorders. By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

DOI: 10.1038/s41586-020-2832-5

Source: https://www.nature.com/articles/s41586-020-2832-5

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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