Lee Ji-Hye
Department of Oral Pathology & Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan 50612, Korea.
Dental Life Science Institute, Pusan National University, Yangsan 50612, Korea.
Exp Neurobiol. 2022 Feb 28;31(1):1-16. doi: 10.5607/en22003.
Patients suffering from rare human diseases often go through a painful journey for finding a definite molecular diagnosis prerequisite of appropriate cures. With a novel variant isolated from a single patient, determination of its pathogenicity to end such "diagnostic odyssey" requires multi-step processes involving experts in diverse areas of interest, including clinicians, bioinformaticians and research scientists. Recent efforts in building large-scale genomic databases and prediction platforms have facilitated identification of potentially pathogenic variants causative of rare human diseases of a Mendelian basis. However, the functional significance of individual variants remains elusive in many cases, thus requiring incorporation of versatile and rapid model organism (MO)-based platforms for functional analyses. In this review, the current scope of rare disease research is briefly discussed. In addition, an overview of invertebrate MOs for their key features relevant to rare neurological diseases is provided, with the characteristics of two representative invertebrate MOs, and , as well as the challenges against them. Finally, recently developed research networks integrating these MOs in collaborative research are portraited with an array of bioinformatical analyses embedded. A comprehensive survey of MO-based research activities provided in this review will help us to design a wellstructured analysis of candidate genes or potentially pathogenic variants for their roles in rare neurological diseases in future.
患有罕见人类疾病的患者通常要经历一段痛苦的历程，才能找到明确的分子诊断结果，而这是进行适当治疗的前提条件。从单个患者中分离出一种新的变异体后，确定其致病性以结束这种“诊断之旅”需要多步骤的过程，涉及不同领域的专家，包括临床医生、生物信息学家和研究科学家。最近在构建大规模基因组数据库和预测平台方面所做的努力，有助于识别导致孟德尔式罕见人类疾病的潜在致病变异体。然而，在许多情况下，单个变异体的功能意义仍然难以捉摸，因此需要纳入基于通用且快速的模式生物（MO）的平台进行功能分析。在这篇综述中，我们简要讨论了罕见病研究的当前范围。此外，还概述了与罕见神经系统疾病相关的关键特征的无脊椎动物模式生物，并介绍了两种代表性无脊椎动物模式生物的特点以及它们面临的挑战。最后，描绘了最近在合作研究中整合这些模式生物的研究网络，并嵌入了一系列生物信息学分析。本综述中对基于模式生物的研究活动的全面调查，将有助于我们未来针对候选基因或潜在致病变异体在罕见神经系统疾病中的作用设计出结构良好的分析方法。
