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科学家绘制出克隆造血中单核苷酸变异和拷贝数改变的联合图谱
作者:小柯机器人 发布时间:2021/7/11 21:48:25

日本京都大学Seishi Ogawa小组绘制出克隆造血中单核苷酸变异和拷贝数改变的联合图谱。相关论文于2021年7月8日在线发表于国际学术期刊《自然—医学》。

研究人员表示,健康个体的克隆造血(CH)与血液系统恶性肿瘤(HM)和心血管疾病的发展有关。先前对CH的研究分析了单核苷酸变异和插入缺失(SNV/indel)或拷贝数改变(CNA),但不能同时分析两者。

结合使用23个CH相关基因的靶向测序以及基于阵列的CNA检测血液来源的DNA,研究人员描绘了来自BioBank Japan队列的11,234个没有HM的CH相关SNV/indel和CNA情况,包括672有后续HM发展的个体,并研究了这些体细胞改变对HM和心血管疾病死亡率的影响,以及对血液学和心血管表型的影响。两种类型的CH相关病变的总数及其克隆大小与血细胞计数异常和HM死亡率呈正相关。CH相关的SNV/indel和CNA在同一个体中表现出统计学上显著的共同发生。

特别是,影响DNMT3A、TET2、JAK2和TP53的SNV/indel和CNA的共同发生导致这些基因的双等位基因改变,并与较高的HM死亡率相关。SNV/indel和CNA的同时发生也调节了心血管死亡率的风险。这些发现强调了在CH评估中同时检测SNV/indel和CNA的重要性。

附:英文原文

Title: Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis

Author: Ryunosuke Saiki, Yukihide Momozawa, Yasuhito Nannya, Masahiro M. Nakagawa, Yotaro Ochi, Tetsuichi Yoshizato, Chikashi Terao, Yutaka Kuroda, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Atsushi Niida, Seiya Imoto, Koichi Matsuda, Takayuki Morisaki, Yoshinori Murakami, Yoichiro Kamatani, Shuichi Matsuda, Michiaki Kubo, Satoru Miyano, Hideki Makishima, Seishi Ogawa

Issue&Volume: 2021-07-08

Abstract: Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11,234individuals without HM from the BioBank Japan cohort, including 672individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH.

DOI: 10.1038/s41591-021-01411-9

Source: https://www.nature.com/articles/s41591-021-01411-9

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex