IDENTIFICATION OF HUMAN GENETIC LOCI WHICH INFLUENCE SUSCEPTIBILITY TO HIV

暴露于艾滋病病毒后的临床病程是高度多变的，这 可变性的部分原因是宿主免疫之间复杂的相互作用。 系统和病毒。许多不同的反应可能是由于 艾滋病毒基因组的异质性；然而，合理地解释 流行病学数据是宿主遗传因素影响易感性 以及对感染和疾病结果的抵抗力，也有助于 对人类对HIV感染的可变宿主反应的观察 人口。这项研究的主要目标是确定这些宿主 控制艾滋病毒感染的遗传因素，免疫反应 感染，以及宿主对各种疗法的反应。 从有艾滋病毒风险的患者身上建立永生B细胞系 与Well参与的临床中心合作的小组 已定义的队列。使用多种方法对基因组DNA进行筛选 检测多态(参见项目Z01CP05678-02 LVC)。通过使用 分子遗传学和群体遗传学的结合，等位基因的扭曲， 临床上连锁的人类基因座的基因类型或连锁平衡 定义的疾病类别，表示基因或DNA片段在 不平衡可能与影响疾病易感性的基因有关 或者抵抗。大约250个限制片段长度 候选基因和等间距基因的多态(RFLP) 在筛选中使用了匿名RFLP标记。一个联网的 监控细胞和DNA库存的数据库，分子试剂， 积累的数据和遗传分析已经建立。

The clinical course following exposure to HIV is highly variable and this variability is due in part to complex interactions between the host immune system and the virus. Much of the differential response may result from heterogeneity of HIV genomes; however, a reasonable interpretation of the epidemiological data is that host genetic factors influence susceptibility and resistance to both infection and disease outcomes and also contribute to the variable host response to HIV infection observed in human populations. The major objective of this study is to identify those host genetic factors that control infection by the HIV, the immune response to that infection, and host reactivity to the various therapeutics. Immortalized B cell lines are being established from patients in HIV risk groups in collaboration with participating clinical centers with well defined cohorts. The genomic DNA is screened using multiple methods to detect polymorphisms (See Project Z01CP05678-02 LVC). By using a combination of molecular and population genetics, distortions of allelic, genotypic, or linkage equilibrium of linked human loci in clinically defined disease categories, signal that the gene or DNA fragment in disequilibrium may be linked to a locus influencing disease susceptibility or resistance. Approximately 250 restriction fragment length polymorphisms (RFLPs) for both candidate genes and equivalently spaced anonymous RFLPs markers are being used in the screenings. A networked data base to monitor cell and DNA inventory, molecular reagents, accumulated data and genetic analysis has been established.