PDF(Pubmed)
Abstract：
Recent progress in human disease genetics is leading to rapid advances in understanding pathobiological mechanisms. However, the sheer number of risk-conveying genetic variants being identified demands in vivo model systems that are amenable to functional analyses at scale. Here we provide a practical guide for using the diploid frog species Xenopus tropicalis to study many genes and variants to uncover conserved mechanisms of pathobiology relevant to human disease. We discuss key considerations in modelling human genetic disorders: genetic architecture, conservation, phenotyping strategy and rigour, as well as more complex topics, such as penetrance, expressivity, sex differences and current challenges in the field. As the patient-driven gene discovery field expands significantly, the cost-effective, rapid and higher throughput nature of Xenopus make it an essential member of the model organism armamentarium for understanding gene function in development and in relation to disease.
摘要：
人类疾病遗传学的最新进展正在导致对病理生物学机制的理解迅速发展。然而,被识别的风险传递遗传变异的绝对数量需要适合大规模功能分析的体内模型系统.在这里，我们为使用二倍体青蛙物种非洲爪鱼研究许多基因和变体以揭示与人类疾病相关的病理生物学的保守机制提供了实用指南。我们讨论了对人类遗传疾病建模的关键考虑因素：遗传结构，养护,表型策略和严谨，以及更复杂的话题，比如外显，表现力，性别差异和该领域当前面临的挑战。随着患者驱动的基因发现领域的显著扩大，成本效益，非洲爪狼的快速和更高通量的性质使其成为模型生物器械的重要成员，以了解基因在发育中的功能以及与疾病的关系。
