Weissenbach J
Généthon, CNRS URA 1922, Evry, France.
Pathol Biol (Paris). 1997 Mar;45(3):205-8.
Until recently, human genome programs focused primarily on establishing maps that would provide signposts to researchers seeking to identify genes responsible for inherited diseases, as well as a basis for genome sequencing studies. Preestablished gene mapping goals have been reached. The over 7,000 microsatellite markers identified to date provide a map of sufficient density to allow localization of the gene of a monogenic disease with a precision of 1 to 2 million base pairs. The physical map, based on systematically arranged overlapping sets of artificial yeast chromosomes (YACs), has also made considerable headway during the last few years. The most recently published map covers more than 90% of the genome. However, currently available physical maps cannot be used for sequencing studies because multiple rearrangements occur in YACs. The recently developed sets of radioinduced hybrids are extremely useful for incorporating genes into existing maps. A network of American and European laboratories has successfully used these radioinduced hybrids to map 15,000 gene tags from large-scale cDNA library sequencing programs. There are increasingly pressing reasons for initiating large scale human genome sequencing studies.
直到最近,人类基因组计划主要致力于绘制图谱,这些图谱能为试图鉴定遗传性疾病相关基因的研究人员提供路标,同时也为基因组测序研究奠定基础。预先设定的基因图谱目标已经实现。迄今已鉴定出的7000多个微卫星标记提供了足够密度的图谱,可将单基因疾病的基因定位在精确到100万至200万碱基对的范围内。基于系统排列的人工酵母染色体(YAC)重叠组构建的物理图谱在过去几年中也取得了显著进展。最近公布的图谱覆盖了90%以上的基因组。然而,目前可用的物理图谱不能用于测序研究,因为YAC中会发生多次重排。最近开发的放射性诱导杂种组对于将基因整合到现有图谱中极为有用。美国和欧洲的实验室网络已成功利用这些放射性诱导杂种对大规模cDNA文库测序计划中的15000个基因标签进行了定位。开展大规模人类基因组测序研究的理由日益迫切。