NIHR Biomedical Research Centre, Wellcome Trust Centre for Human Genetics, Oxford, UK.
J Hum Genet. 2012 Jan;57(1):70-2. doi: 10.1038/jhg.2011.128. Epub 2011 Dec 1.
The development of next generation sequencing (NGS) has radically transformed the scientific landscape, making it possible to sequence the exome of any given individual in a cost-effective way. The power of this approach has been demonstrated by a number of groups who have identified pathogenic mutations in small pedigrees that have been resistant to traditional genetic mapping. Recently it has become clear that exome sequencing has great potential with respect to sporadic disease and the identification of de novo mutations. This is highlighted by studies reporting whole-exome sequencing of patient-parental trios affected by learning disability, autism and schizophrenia. It is widely anticipated that the introduction of this technique into a clinical setting will revolutionise genetic diagnosis. However, the sensitivity of NGS exome sequencing is currently unclear. Here, we describe the exome sequencing of DNA samples from a patient with double cortex syndrome and her parents, resulting in the detection of a mosaic splicing mutation in LIS1. This variant was found at an allele frequency of just 18%, demonstrating that NGS methods have the capacity to identify pathogenic mosaic mutations present at a low level.
下一代测序 (NGS) 的发展彻底改变了科学领域，使得以经济有效的方式对任何给定个体的外显子组进行测序成为可能。许多研究小组已经证明了这种方法的强大之处，他们在一些传统遗传图谱难以定位的小家族中发现了致病性突变。最近，外显子组测序在散发性疾病和新生突变的鉴定方面具有很大的潜力，这一点已得到了研究报告的证实，这些报告对受学习障碍、自闭症和精神分裂症影响的患者-父母三人组进行了全外显子组测序。人们普遍预期，将这项技术引入临床环境将彻底改变遗传诊断。然而，NGS 外显子组测序的灵敏度目前尚不清楚。在这里，我们描述了一位患有双皮质综合征的患者及其父母的 DNA 样本的外显子组测序，结果检测到 LIS1 中的镶嵌剪接突变。该变体的等位基因频率仅为 18%，表明 NGS 方法有能力识别低水平存在的致病性镶嵌突变。
