GENETIC LINKAGE MAP OF HUMAN CHROMOSOME 9

这项研究计划的目标是开发一种高分辨率 人类9号染色体的遗传连锁图谱。这样的图谱将有助于 人类疾病基因的识别和定位。此外， 基因图谱是准确检测携带者和 遗传性疾病的产前诊断。这样做的第一个目的是 研究目的是识别高度多态的简单序列重复标记 它跨越了9号染色体的长度。这将通过 筛选粘粒重复序列文库，亚克隆阳性 Cosmids和测序以确定聚合酶链式反应(PCR)引物。随后，CEPH 参考家系将使用这些标记和一个遗传基因进行基因分型 利用计算机程序LINKING和CRIMAP构建的连锁图谱。 如果发现现有的9号染色体探针占据了 将对连锁图谱、插入片段进行重复筛选和测序 以便于进行PCR基因分型。序列标记的站点(STS)将是 为所有探测器标识，以便于比较 基因图谱和物理图谱。最终，人类的遗传连锁图谱 使用STSS识别的标记构建的9号染色体将导致 许多人类疾病基因的物理定位和克隆： 包括结节性硬化症、Friedreich‘s共济失调和扭转 肌张力障碍。

The objective of this research plan is to develop a high resolution genetic linkage map of human chromosome 9. Such maps will facilitate the identification and localization of human disease genes. Furthermore, genetic maps are a prerequisite for accurate carrier detection and prenatal diagnosis of hereditary disorders. The first aim of this research is to identify highly polymorphic simple sequence repeat markers that span the length of chromosome 9. This will be accomplished by screening a cosmid library for repeat sequences, subcloning positive cosmids, and sequencing to identify PCR primers. Subsequently, the CEPH reference pedigrees will be genotyped using these markers and a genetic linkage map constructed using the computer programs LINKAGE and CRIMAP. If existing chromosome 9 probes are found to occupy critical regions in the linkage map, the inserts will be screened for repeats and sequenced to facilitate PCR genotyping. Sequence tagged sites (STSs) will be identified for all probes in order to facilitate comparison of the genetic and physical maps. Ultimately, a genetic linkage map of human chromosome 9 constructed using markers identified by STSs will lead to the physical localization and cloning of many human disease genes: including those for tuberous sclerosis, Friedreich's ataxia, and torsion dystonia.