Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
Trends Genet. 2011 Jun;27(6):217-23. doi: 10.1016/j.tig.2011.03.002. Epub 2011 Apr 14.
From the fertilization of an egg until the death of an individual, somatic cells can accumulate genetic changes, such that cells from different tissues or even within the same tissue differ genetically. The presence of multiple cell clones with distinct genotypes in the same individual is referred to as 'somatic mosaicism'. Many endogenous factors such as mobile elements, DNA polymerase slippage, DNA double-strand break, inefficient DNA repair, unbalanced chromosomal segregation and some exogenous factors such as nicotine and UV exposure can contribute to the generation of somatic mutations, thereby leading to somatic mosaicism. Such changes can potentially affect the epigenetic patterns and levels of gene expression, and ultimately the phenotypes of cells. Although recent studies suggest that somatic mosaicism is widespread during normal development and aging, its implications for heightened disease risks are incompletely understood. Here, I discuss the origins, prevalence and implications of somatic mosaicism in healthy human tissues.
从卵子受精到个体死亡，体细胞可以积累遗传变化，使得来自不同组织甚至同一组织的细胞在遗传上存在差异。同一个体中存在具有不同基因型的多个细胞克隆被称为“体细胞嵌合现象”。许多内源性因素，如移动元件、DNA 聚合酶滑动、DNA 双链断裂、低效的 DNA 修复、不平衡的染色体分离以及一些外源性因素，如尼古丁和 UV 暴露，都可能导致体细胞突变的产生，从而导致体细胞嵌合现象。这些变化可能潜在地影响表观遗传模式和基因表达水平，并最终影响细胞的表型。尽管最近的研究表明，体细胞嵌合现象在正常发育和衰老过程中广泛存在，但它对疾病风险增加的影响尚不完全清楚。在这里，我讨论了健康人体组织中体细胞嵌合现象的起源、普遍性和意义。
