A COMPLETE GENETIC LINKAGE MAP OF THE HUMAN GENOME

我们的长期目标是建造一个5厘米摩根 人类基因组的分辨率遗传连锁图谱。这将会 提供宝贵的资源，我们打算提供给 对绘制和克隆基因感兴趣的研究人员负责 治疗孟德尔病症。此外，可获得一种基因 地图将有助于构建人类的物理地图 基因组。这个项目的具体目标是：1)填补 我们当前的地图通过识别来自 染色体特异文库和整合RFLP 被其他研究人员识别到现有地图中，2)建立 现有连杆组的物理终点由原位确定 最远端标记的杂交，并将图谱扩展到 在染色体末端加入已知的 在这些区域或通过识别已知远端附近的新RFLP 非多态DNA片段，3)定义和发展 RFLP标记(“基因组试剂盒”)将提供足够的 覆盖每条染色体以实现高效的未来遗传 绘制致病因素图，4)定义和开发一个小组 适合于染色体鉴定的RFLP标记 通过RFLP等位基因杂合性缺失，以及 5)改造CRI-MAP多基因座连锁分析计算机 程序打包成通用的形式，并开始 开发测试“同时搜索”的程序 由Lander和Botstein(1987)提出的识别方法 涉及复杂或异质性的多个基因 精神错乱。地图和相关资源的开发将 1)立即确定新基因的染色体位置 联系，2)使开发更准确的信息 遗传病的症状前诊断试验，3)使 寻找和克隆致病基因将被进行 以一种更有效的方式，使绘制复杂的地图成为可能 遗传性疾病，以及5)允许人们检测和定义极限 一些染色体特有的缺失是某些 肿瘤疾病。从长远来看，基因图谱和 相关资源可能会被证明有助于开发 更好地理解分子遗传机制 许多疾病的潜在原因，并最终改善了治疗 治疗或治愈的方法。

Our long-term objective is to construct a 5 centiMorgan resolution genetic linkage map of the human genome. This would provide a valuable resource which we intend to make available to interested investigators for mapping and cloning genes responsible for Mendelian disorders. In addition, the availability of a genetic map would facilitate construction of a physical map of the human genome. The specific aims of this project are to 1) fill in gaps in our current map by identifying new polymorphisms from chromosome specific libraries and by incorporating RFLPs identified by other researchers into the existing map, 2) establish the physical end points of the existing linkage groups by in situ hybridization of the most distal markers, and extend the maps to the ends of the chromosomes by incorporating RFLPs known to lie in these regions or by identifying new RFLPs near known distal nonpolymorphic DNA segments, 3) define and develop subsets of RFLP markers ("genome kits") that will provide adequate coverage of each chromosome for efficient future genetic mapping of disease causing agents, 4) define and develop a panel of RFLP markers suited for identification of chromosome deletions through the loss of heterozygosity of RFLP alleles, and 5) covert the CRI-MAP multilocus linkage analysis computer program package into a form for general use, and begin development of programs to test the "simultaneous search" method proposed by Lander and Botstein (1987) for identification of multiple genes implicated in complex or heterogeneous disorders. Development of the map and related resources would 1) identify immediately the chromosomal location of new linkages, 2) enable development of more accurate informative tests for presymptomatic diagnosis of genetic diseases, 3) enable searches for and cloning of disease causing genes to be conducted in a more efficient manner, 4) make it possible to map complex genetic disorders, and 5) allow one to detect and define the limits of chromosomal specific deletions that are characteristic of some neoplastic disorders. In the long-term, the genetic map and related resources will likely prove instrumental in developing a better understanding of the molecular genetic mechanism underlying many diseases, and ultimately improved therapeutic approaches for treatment or cure.