Wheway Gabrielle, Mitchison Hannah M
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Genetics and Genomic Medicine, University College London, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Front Genet. 2019 Mar 11;10:127. doi: 10.3389/fgene.2019.00127. eCollection 2019.
Cilia are highly specialized cellular organelles that serve multiple functions in human development and health. Their central importance in the body is demonstrated by the occurrence of a diverse range of developmental disorders that arise from defects of cilia structure and function, caused by a range of different inherited mutations found in more than 150 different genes. Genetic analysis has rapidly advanced our understanding of the cell biological basis of ciliopathies over the past two decades, with more recent technological advances in genomics rapidly accelerating this progress. The 100,000 Genomes Project was launched in 2012 in the UK to improve diagnosis and future care for individuals affected by rare diseases like ciliopathies, through whole genome sequencing (WGS). In this review we discuss the potential promise and medical impact of WGS for ciliopathies and report on current progress of the 100,000 Genomes Project, reviewing the medical, technical and ethical challenges and opportunities that new, large scale initiatives such as this can offer.
纤毛是高度特化的细胞器，在人类发育和健康中发挥多种功能。超过150种不同基因中发现的一系列不同遗传突变导致纤毛结构和功能缺陷，进而引发多种发育障碍，这证明了纤毛在人体中的核心重要性。在过去二十年中，遗传分析迅速增进了我们对纤毛病细胞生物学基础的理解，而基因组学领域最近的技术进步更是加速了这一进程。2012年，英国启动了“十万基因组计划”，通过全基因组测序（WGS）改善对纤毛病等罕见病患者的诊断和后续治疗。在这篇综述中，我们讨论了全基因组测序对纤毛病的潜在前景和医学影响，并报告了“十万基因组计划”的当前进展，审视了此类新的大规模计划可能带来的医学、技术和伦理挑战与机遇。
