Research efforts over the past decade have defined the genetic landscape of somatic variation in the brain. Neurons accumulate somatic mutations from development through aging with potentially profound functional consequences. Recent studies have revealed the contribution of somatic mosaicism to various brain disorders including focal epilepsy, neuropsychiatric disease, and neurodegeneration. One notable finding is that the effect of somatic mosaicism on clinical outcomes can vary depending on contextual factors, such as the developmental origin of a variant or the number and type of cells affected. In this review, we highlight current knowledge regarding the role of somatic mosaicism in brain disorders and how biological context can mediate phenotypes. First, we identify the origins of brain somatic variation throughout the lifespan of an individual. Second, we explore recent discoveries that suggest somatic mosaicism contributes to various brain disorders. Finally, we discuss neuropathological associations of brain mosaicism in different biological contexts and potential clinical utility.

中文翻译：

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脑部疾病中的躯体嵌合体


过去十年的研究工作已经确定了大脑体细胞变异的遗传景观。神经元从发育到衰老积累体细胞突变，可能产生深远的功能后果。最近的研究揭示了体细胞嵌合体对各种脑部疾病的贡献，包括局灶性癫痫、神经精神疾病和神经退行性变。一个值得注意的发现是，体细胞嵌合体对临床结果的影响可能因环境因素而异，例如变异的发育起源或受影响细胞的数量和类型。在这篇综述中，我们强调了关于体细胞嵌合体在脑部疾病中的作用以及生物学环境如何介导表型的当前知识。首先，我们确定了个体整个生命周期中脑体变异的起源。其次，我们探讨了最近的发现，这些发现表明体细胞嵌合体会导致各种脑部疾病。最后，我们讨论了大脑嵌合体在不同生物学背景下的神经病理学关联和潜在的临床用途。