Somatic mosaicism: implications for the cardiovascular system.
Somatic mosaicism: implications for the cardiovascular system.
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体细胞镶嵌：对心血管系统的影响。
DOI：
10.1093/eurheartj/ehz907
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发表时间：
2020
影响因子：
39.3
通讯作者：
Walsh,Kenneth
中科院分区：
文献类型：
--
作者：
Sano,Soichi;Wang,Ying;Walsh,Kenneth
没有两个人是一样的，因为我们包含不同的遗传密码，因人而异，使我们独一无二。然而，越来越多的证据表明，在同一个人的基因组也不同，从细胞到细胞。这种现象被称为体细胞嵌合现象，它是由胚胎发育过程中和个体一生中不可避免地发生的体细胞突变的积累引起的。事实上，DNA测序方法的最新进展表明，体细胞突变在正常细胞中比我们最初想象的要普遍得多。在大多数情况下，这些突变是表型中性的，对细胞或生物体没有影响。如果突变赋予有害的表型，则该细胞可能随着时间的推移而从生物体中丢失，因为它与正常细胞竞争。相比之下，“驱动”基因突变可以赋予适应性优势，导致携带突变的细胞的克隆扩增。虽然人们已经确定，赋予健康的突变的积累可能有助于癌症的发展，但最近的证据表明，它们在无症状个体的正常组织中非常普遍。此外，越来越明显的是，这些异常的克隆扩增可能是老年人非癌性疾病发展的先兆。在这里，我们总结了最近的研究结果，记录了不同组织中体细胞嵌合体的程度，并讨论了这些体细胞突变可以影响各种年龄相关疾病，包括心血管疾病的挑衅性想法。
No two individuals are alike as we contain different genetic codes that vary from person-to-person and make us unique. However, increasing evidence shows that within the same individual the genome also differs from cell-to-cell. This phenomenon is known as somatic mosaicism, and it results from the accumulation of somatic mutations that inevitably occur during embryonic development and over the course of an individual’s lifetime. Indeed, recent advances in DNA sequencing methodology reveal that somatic mutations are much more prevalent in normal cells than we initially thought. In most cases, these mutations are phenotypically neutral and there are no consequences on the cell or organism. If the mutation confers a deleterious phenotype, that cell may be lost from the organism over time as it competes with normal cells. In contrast, a ‘driver’gene mutation can confer a fitness advantage that leads to the clonal expansion of the cell that harbours the mutation. While it is wellestablished that the accumulation of fitness-conferring mutations can contribute to the development of cancer, recent evidence suggests that they are remarkably prevalent in the normal tissues of nonsymptomatic individuals. Furthermore, it is becoming increasingly apparent that these aberrant clonal expansions can be harbingers of non-cancerous disease development in elderly individuals. Here, we summarize recent findings that document the extents of somatic mosaicism in different tissues and discuss the provocative idea that these somatic mutations can impact various age-associated diseases including cardiovascular disease.