Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
The Centre for Applied Genomics (TCAG), The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Genes (Basel). 2022 Jan 24;13(2):207. doi: 10.3390/genes13020207.
Rare post-zygotic mutations in the brain are now known to contribute to several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due to the limited availability of brain tissue, most studies rely on estimates of mosaicism from peripheral samples. In this study, we undertook whole exome sequencing on brain tissue from 26 ASD brain donors from the Harvard Brain Tissue Resource Center (HBTRC) and ascertained the presence of post-zygotic and germline mutations categorized as pathological, including those impacting known ASD-implicated genes. Although quantification did not reveal enrichment for post-zygotic mutations compared with the controls ( = 15), a small number of pathogenic, potentially ASD-implicated mutations were identified, notably in and . Furthermore, germline mutations were identified in the same tissue samples in several key ASD genes, including , , and The establishment of tissue resources that are available to the scientific community will facilitate the discovery of new mutations for ASD and other neurodevelopmental disorders.
现在已知，胚胎后基因突变会导致多种神经发育障碍，包括自闭症谱系障碍（ASD）。然而，由于脑组织的可用性有限，大多数研究依赖于外周样本的嵌合体估计。在这项研究中，我们对来自哈佛脑组织资源中心（HBTRC）的 26 名 ASD 脑捐赠者的脑组织进行了全外显子组测序，并确定了存在胚后和种系突变，这些突变被归类为病理性突变，包括那些影响已知的 ASD 相关基因的突变。虽然与对照组相比（=15），定量分析并未显示胚后突变的富集，但仍发现了少数潜在的致病性 ASD 相关突变，特别是在 和 中。此外，在几个关键的 ASD 基因中，包括 、 、和 ，在相同的组织样本中也发现了种系突变。建立可供科学界使用的组织资源将有助于发现 ASD 和其他神经发育障碍的新突变。
