The identification of the genes underlying monogenic diseases has been of interest to clinicians and scientists for many years. Using inherited retinal dystrophies as an example of monogenic disease we describe the history of molecular genetic techniques that have been pivotal in the discovery of disease causing genes. The methods that were developed in the 1970's and 80's are still in use today but have been refined and improved. These techniques enabled the concept of the Human Genome Project to be envisaged and ultimately realised. When the successful conclusion of the project was announced in 2003 many new tools and, as importantly, many collaborations had been developed that facilitated a rapid identification of disease genes. In the post-human genome project era advances in computing power and the clever use of the properties of DNA replication has allowed the development of next-generation sequencing technologies. These methods have revolutionised the identification of disease genes because for the first time there is no need to define the position of the gene in the genome. The use of next generation sequencing in a diagnostic setting has allowed many more patients with an inherited retinal dystrophy to obtain a molecular diagnosis for their disease. The identification of novel genes that have a role in the development or maintenance of retinal function is opening up avenues of research which will lead to the development of new pharmacological and gene therapy approaches. Neither of which can be used unless the defective gene and protein is known. The continued development of sequencing technologies also holds great promise for the advent of truly personalised medicine.

多年以来，对单基因疾病的潜在基因进行鉴定一直是临床医生和科学家关注的问题。以遗传性视网膜营养不良为例，以单基因疾病为例，我们描述了分子遗传学技术的历史，这些技术在发现致病基因方面具有举足轻重的地位。1970年代和80年代开发的方法至今仍在使用，但已经过改进和改进。这些技术使人们可以设想并最终实现人类基因组计划的概念。当2003年宣布该项目成功结束时，许多新工具，更重要的是，已经开展了许多合作，促进了疾病基因的快速鉴定。在后人类基因组计划时代，计算能力不断提高，DNA复制特性的巧妙运用使下一代测序技术得以发展。这些方法彻底改变了疾病基因的鉴定，因为这是第一次无需定义基因在基因组中的位置。在诊断环境中使用下一代测序已使更多患有遗传性视网膜营养不良的患者获得了对其疾病的分子诊断。鉴定在视网膜功能的发展或维持中起作用的新基因正在开拓研究途径，这将导致新的药理学和基因治疗方法的发展。除非已知有缺陷的基因和蛋白质，否则都不能使用。