Dumanski Jan P, Piotrowski Arkadiusz
Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Methods Mol Biol. 2012;838:249-72. doi: 10.1007/978-1-61779-507-7_12.
Somatic mosaicism is the result of postzygotic de novo mutation occurring in a portion of the cells making up an organism. Structural genetic variation is a very heterogeneous group of changes, in terms of numerous types of aberrations that are included in this category, involvement of many mechanisms behind the generation of structural variants, and because structural variation can encompass genomic regions highly variable in size. Structural variation rapidly evolved as the dominating type of changes behind human genetic diversity, and the importance of this variation in biology and medicine is continuously increasing. In this review, we combine the evidence of structural variation in the context of somatic cells. We discuss the normal and disease-related somatic structural variation. We review the recent advances in the field of monozygotic twins and other models that have been studied for somatic mutations, including other vertebrates. We also discuss chromosomal mosaicism in a few prime examples of disease genes that contributed to understanding of the importance of somatic heterogeneity. We further highlight challenges and opportunities related to this field, including methodological and practical aspects of detection of somatic mosaicism. The literature devoted to interindividual variation versus papers reporting on somatic variation suggests that the latter is understudied and underestimated. It is important to increase our awareness about somatic mosaicism, in particular, related to structural variation. We believe that further research of somatic mosaicism will prove beneficial for better understanding of common sporadic disorders.
体细胞嵌合现象是由构成生物体的一部分细胞中发生的合子后新发突变导致的。结构遗传变异是一组非常异质的变化，这是因为该类别中包含多种类型的畸变，结构变异产生背后涉及多种机制，还因为结构变异可涵盖大小高度可变的基因组区域。结构变异迅速演变成人类遗传多样性背后的主要变化类型，并且这种变异在生物学和医学中的重要性也在不断增加。在本综述中，我们结合了体细胞背景下结构变异的证据。我们讨论了正常和与疾病相关的体细胞结构变异。我们回顾了在同卵双胞胎以及其他针对体细胞突变进行研究的模型领域（包括其他脊椎动物）的最新进展。我们还在一些有助于理解体细胞异质性重要性的疾病基因的典型例子中讨论了染色体嵌合现象。我们进一步强调了与该领域相关的挑战和机遇，包括体细胞嵌合现象检测的方法学和实际操作方面。致力于个体间变异的文献与报道体细胞变异的论文相比表明，后者的研究不足且被低估。提高我们对体细胞嵌合现象（特别是与结构变异相关的）的认识非常重要。我们相信，对体细胞嵌合现象的进一步研究将有助于更好地理解常见的散发性疾病。
