Abstract：
Over the past decade high-throughput DNA sequencing approaches, namely whole exome and whole genome sequencing became a standard procedure in Mendelian disease diagnostics. Implementation of these technologies greatly facilitated diagnostics and shifted the analysis paradigm from variant identification to prioritisation and evaluation. The diagnostic rates vary widely depending on the cohort size, heterogeneity and disease and range from around 30% to 50% leaving the majority of patients undiagnosed. Advances in omics technologies and computational analysis provide an opportunity to increase these unfavourable rates by providing evidence for disease-causing variant validation and prioritisation. This review aims to provide an overview of the current application of several omics technologies including RNA-sequencing, proteomics, metabolomics and DNA-methylation profiling for diagnostics of rare genetic diseases in general and inborn errors of metabolism in particular.
摘要：
在过去的十年中，高通量DNA测序方法，即全外显子组和全基因组测序成为孟德尔疾病诊断的标准程序。这些技术的实施极大地促进了诊断，并将分析范式从变体识别转变为优先级和评估。诊断率因队列大小而异，异质性和疾病，范围从30%到50%左右，大多数患者未被诊断。组学技术和计算分析的进步提供了一个机会，以增加这些不利的比率，通过提供证据的致病变异验证和优先排序。这篇综述旨在概述几种组学技术的当前应用，包括RNA测序，蛋白质组学，代谢组学和DNA甲基化分析用于诊断一般罕见遗传病，特别是先天性代谢错误。
