Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
Genalice Core BV, Nijkerk, The Netherlands.
Hum Mutat. 2018 Oct;39(10):1393-1401. doi: 10.1002/humu.23586. Epub 2018 Jul 18.
Postzygotic mutations are DNA changes acquired from the zygote stage onwards throughout the lifespan. These changes lead to differences in DNA sequence among cells of an individual, potentially contributing to the etiology of complex disorders. Here we compared whole genome DNA sequence data of two monozygotic twin pairs, 40 and 100 years old, to detect somatic mosaicism. DNA samples were sequenced twice on two Illumina platforms (13X and 40X read depth) for increased specificity. Using differences in allelic ratios resulted in sets of 1,720 and 1,739 putative postzygotic mutations in the 40-year-old twin pair and 100-year-old twin pair, respectively, for subsequent enrichment analysis. This set of putative mutations was strongly (p < 4.37e-91) enriched in both twin pairs for regulatory elements. The corresponding genes were significantly enriched for genes that are alternatively spliced, and for genes involved in GTPase activity. This research shows that somatic mosaicism can be detected in monozygotic twin pairs by using allelic ratios calculated from DNA sequence data and that the mutations which are found by this approach are not randomly distributed throughout the genome.
合子后突变是指从受精卵阶段开始，在整个生命周期中获得的 DNA 变化。这些变化导致个体细胞之间的 DNA 序列存在差异，可能导致复杂疾病的病因。在这里，我们比较了两对年龄分别为 40 岁和 100 岁的同卵双胞胎的全基因组 DNA 序列数据，以检测体细胞镶嵌现象。为了提高特异性，对 DNA 样本进行了两次测序，使用了两个 Illumina 平台（13X 和 40X 读深度）。使用等位基因比率的差异，在 40 岁双胞胎和 100 岁双胞胎中分别产生了 1720 和 1739 个可能的合子后突变的集合，用于随后的富集分析。这组可能的突变在两个双胞胎组中都强烈（p < 4.37e-91）富集在调控元件中。相应的基因在剪接方式不同的基因和参与 GTP 酶活性的基因中显著富集。这项研究表明，通过使用从 DNA 序列数据计算的等位基因比率，可以在同卵双胞胎中检测到体细胞镶嵌现象，并且通过这种方法发现的突变不是随机分布在整个基因组中的。
