Folkhälsan Research Center, Helsinki, Finland.
Department of Medical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
J Neuromuscul Dis. 2020;7(3):203-216. doi: 10.3233/JND-190459.
Human genes have a variable length. Those having a coding sequence of extraordinary length and a high number of exons were almost impossible to sequence using the traditional Sanger-based gene-by-gene approach. High-throughput sequencing has partly overcome the size-related technical issues, enabling a straightforward, rapid and relatively inexpensive analysis of large genes.Several large genes (e.g. TTN, NEB, RYR1, DMD) are recognized as disease-causing in patients with skeletal muscle diseases. However, because of their sheer size, the clinical interpretation of variants in these genes is probably the most challenging aspect of the high-throughput genetic investigation in the field of skeletal muscle diseases.The main aim of this review is to discuss the technical and interpretative issues related to the diagnostic investigation of large genes and to reflect upon the current state of the art and the future advancements in the field.
人类基因的长度具有可变性。那些编码序列特别长且外显子数量众多的基因，几乎不可能使用传统的基于桑格的逐个基因方法进行测序。高通量测序在一定程度上克服了与大小相关的技术问题，能够直接、快速且相对廉价地分析大型基因。一些大型基因（例如 TTN、NEB、RYR1、DMD）在患有骨骼肌疾病的患者中被认为是致病基因。然而，由于其庞大的体积，这些基因中的变异的临床解释可能是骨骼肌疾病高通量基因研究领域中最具挑战性的方面。本文的主要目的是讨论与大型基因诊断研究相关的技术和解释问题，并反思该领域的当前现状和未来进展。
