Deep sequencing reveals variations in somatic cell mosaic mutations between monozygotic twins with discordant psychiatric disease.
Deep sequencing reveals variations in somatic cell mosaic mutations between monozygotic twins with discordant psychiatric disease.
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DOI：
10.1038/hgv.2017.32
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发表时间：
2017
影响因子：
1.5
通讯作者：
Kurotaki N
中科院分区：
文献类型：
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作者：
Morimoto Y;Ono S;Imamura A;Okazaki Y;Kinoshita A;Mishima H;Nakane H;Ozawa H;Yoshiura KI;Kurotaki N
单卵双胞胎（MZ）被认为是基因相同的。然而，最近的研究表明它们之间存在不一致的变异。我们进行了全外显子组测序（WES）在五个MZ双胞胎对不一致的神经发育障碍和一个健康对照MZ双胞胎检测不一致的变异。我们通过个性化下一代测序（NGS）分析后，通过深度测序确认了三个不一致的变体。在FBXO 38（chr 5：147774428;T>G）、SMOC 2（chr 6：169051385;A>G）和TDRP（chr 8：442616;A>G）中检测到三个突变，在深度测序上突变等位基因的等位基因频率较低，表明这些基因座由于发育阶段的体细胞突变而为嵌合体。我们的研究结果表明，深度测序分析将是一种足够的方法来检测负责遗传性疾病的候选基因中的不一致突变。
Monozygotic (MZ) twins have been thought to be genetically identical. However, recent studies have shown discordant variants between them. We performed whole-exome sequencing (WES) in five MZ twin pairs with discordant neurodevelopmental disorders and one healthy control MZ twin to detect discordant variants. We identified three discordant variants confirmed by deep sequencing after analysis by personalized next-generation sequencing (NGS). Three mutations in FBXO38 (chr5:147774428;T>G), SMOC2 (chr6:169051385;A>G) and TDRP (chr8:442616;A>G), were detected with low allele frequency of mutant alleles on deep sequencing, suggesting that these loci are mosaic due to somatic mutations in a developmental stage. Our results suggest that deep sequencing analysis would be an adequate method to detect discordant mutations in candidate genes responsible for heritable diseases.