Comprehensive validation of a diagnostic strategy for sequencing genes with one or multiple pseudogenes, using pseudoxanthoma elasticum as a model

We propose a diagnostic strategy for the molecular diagnosis of genes with one or more known pseudogene(s) with next-generation sequencing (NGS), using pseudoxanthoma elasticum and ABCC6 as an example. Indeed, the use of NGS for analysis of such genes can be complicated by false positive and negative results. We show in this paper that in contrast to whole exome sequencing, a combined approach of PCR-based targeted enrichment with an adapted mapping algorithm circumvents aspecificities due to pseudogenes in a reliable way.本研究提出一种针对携带一个或多个已知假基因的基因，利用下一代测序（next-generation sequencing, NGS）实施分子诊断的策略，并以弹性假黄瘤（pseudoxanthoma elasticum）相关基因ABCC6作为研究示例。事实上，利用NGS分析此类基因时，易受假基因干扰产生假阳性与假阴性结果，导致分析流程复杂化。本研究证实，相较于全外显子测序，基于PCR的靶向富集与适配型比对算法相结合的联合策略，可可靠规避假基因引发的非特异性分析问题。