A Post-Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases
A Post-Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases
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DOI：
10.1002/humu.22450
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发表时间：
2013-12-01
期刊：
影响因子：
3.9
通讯作者：
Nelen, Marcel R.
中科院分区：
文献类型：
--
作者：
Neveling, Kornelia;Feenstra, Ilse;Nelen, Marcel R.
大规模并行测序的出现正在迅速改变用于涉及大量基因的罕见疾病的遗传诊断和研究的策略。到目前为止，还不清楚这些方法是否像临床医生所要求的那样，显著优于传统的单基因检测。这种传统诊断方法目前的产量取决于一系列因素，包括基因特定的表型特征，以及特定基因参与的相对频率。为了评估分子诊断学中正在发生的范式转变的影响，我们评估了传统的基于桑格的测序(2011年)和外显子组测序，然后是定向生物信息学分析(2012年)，对五种高度异质性的不同情况进行了评估，我们的中心为这些情况提供分子诊断。我们发现，外显子组测序对耳聋、失明、线粒体疾病和运动障碍的诊断比桑格测序有更高的诊断效率。对于微卫星稳定的结直肠癌，在两种策略下这一比例都较低。即使所有本可以由医生订购的基因都进行了测试，外显子组捕获的更多基因仍然会带来明显更好的诊断结果，而成本只有它的一小部分。(C)2013年威利期刊公司。
The advent of massive parallel sequencing is rapidly changing the strategies employed for the genetic diagnosis and research of rare diseases that involve a large number of genes. So far it is not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. The current yield of this traditional diagnostic approach depends on a complex of factors that include gene-specific phenotype traits, and the relative frequency of the involvement of specific genes. To gauge the impact of the paradigm shift that is occurring in molecular diagnostics, we assessed traditional Sanger-based sequencing (in 2011) and exome sequencing followed by targeted bioinformatics analysis (in 2012) for five different conditions that are highly heterogeneous, and for which our center provides molecular diagnosis. We find that exome sequencing has a much higher diagnostic yield than Sanger sequencing for deafness, blindness, mitochondrial disease, and movement disorders. For microsatellite-stable colorectal cancer, this was low under both strategies. Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost. (C) 2013 Wiley Periodicals, Inc.