A COMPLETE GENETIC LINKAGE MAP OF THE HUMAN GENOME

我们的长期目标是建立一个5厘摩根 人类基因组的高分辨率遗传连锁图。 这将 提供了一个宝贵的资源，我们打算提供给 感兴趣的研究人员绘制和克隆基因负责 孟德尔遗传病的治疗方法 此外，基因的可用性 地图将有助于构建人类的物理地图， 基因组 该项目的具体目标是：1）填补以下方面的空白： 我们目前的地图，通过识别新的多态性， 染色体特异性文库和通过掺入RFLP 其他研究人员在现有地图上发现的，2）建立 现有连接基团的物理端点， 杂交的最远端标记，并扩展地图， 染色体的末端，通过引入已知位于 在这些区域中，或者通过在已知的远端区域附近识别新的RFLP， 非多态性DNA片段，3）定义和开发 RFLP标记（“基因组试剂盒”），将提供足够的 每个染色体的覆盖率，以实现未来的高效遗传 绘制致病因子图，4）确定和开发一个小组 适合染色体鉴定的RFLP标记 通过RFLP等位基因的杂合性缺失而导致的缺失，以及 5)转换CRI-MAP多位点连锁分析计算机 程序包转换成一个通用的表单，然后开始 开发测试“同时搜索”的程序 Lander和Botstein（1987）提出的识别方法 多个基因参与了复杂或异质的 紊乱 地图和相关资源的开发将 1)立即确定新的染色体位置， （2）能够制定更准确的信息 遗传疾病的症状前诊断测试，3）使 研究和克隆致病基因， （4）使其能够以更有效方式， 遗传性疾病，5）允许人们检测和定义限制 染色体特异性缺失的特征， 肿瘤性疾病 从长远来看，基因图谱和 相关资源可能有助于制定一项 更好地理解分子遗传机制 许多疾病的基础，并最终改善治疗 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.