GENETIC ANALYSIS OF HIV RESTRICTION AND TUMOR SUPPRESSOR GENES

癌症和艾滋病是复杂的疾病，由 环境和寄主的遗传因素。一些继承的 癌症综合症已经被描述过了，负责 这些遗传病中的几种已经被确认。从基因上讲 遗传性癌症遵循肿瘤抑制模型，由此丢失 一个对正常生长控制很重要的基因的功能会导致恶性肿瘤。 肿瘤抑制基因也在零星的恶性肿瘤中发挥作用。在艾滋病方面-- 相关疾病，对病毒反应的广泛异质性 这表明宿主中的遗传因素在疾病中发挥了作用。 对两人都被感染的兄弟姐妹的分析表明， 是修饰或限制基因。对其中每一种的遗传分析 疾病需要在基因中获得遗传标记，这些基因可能是 候选基因。尽管超过5,000个人类限制性片段长度 已经描述了基因的多态，只有1500个在编码基因中。这 代表了50-100,000个基因中的一小部分。我们已经雇佣了 描述多态的标准方法和新方法 在具有重要生物学意义的人类基因中。(1)单链构象- 本研究采用基因分型技术，对非白粉病患者进行了基因分型。 基因的编码部分。(2)微卫星座位的高度多态 而邻近的基因使得重要区域的详细遗传图谱 将被生成。(3)Not I限制酶切位点周围的序列 3号染色体已被用作表达序列的标记，并 产生遗传标记。在IKB中描述了多态现象 基因(作用于艾滋病毒的转录因子的抑制物)和 免疫球蛋白重链基因。这些标记将在一个 一群感染艾滋病毒的人。超过20个代表表达的基因座 序列已被定位在3号染色体上，这是一条参与 多种恶性肿瘤的细胞遗传学异常。这些表达了 序列标记将用于鉴定可能的肿瘤抑制基因 精神错乱。新生基底细胞癌的精细结构遗传图谱 已构建了证候区域。

Cancer and AIDS represent complex diseases that are controlled by the environment and by genetic factors of the host. A number of inherited cancer syndromes have been described, and the genes responsible for several of these genetic diseases have been identified. Genetically inherited cancers follow the tumor suppressor model, whereby the loss of function of a gene important to normal growth control leads to malignancy. Tumor suppressor genes also play a role in sporadic malignancies. In HIV- related disease, extensive heterogeneity in the response to the virus suggests that genetic factors in the host play a role in the disease. Analysis of siblings that have both become infected suggests that there are modifying or restriction genes. Genetic analysis of each of these diseases requires the availability of genetic markers in genes that may be candidate genes. Although over 5,000 human restriction fragment length polymorphisms have been described, only 1,500 are in coding genes. This represents a small proportion of the 50-100,000 genes. We have employed standard approaches as well as new methods to characterize polymorphisms in biologically important human genes. (1) The single-stranded conforma- tion polymorphism method has been used to identify polymorphisms in non- coding portions of genes. (2) Highly polymorphic microsatellite loci in and near genes have allowed detailed genetic maps of important regions to be generated. (3) Sequences surrounding Not I restriction sites in chromosome 3 have been used as markers for expressed sequences, and to generate genetic markers. Polymorphisms have been described in the IKB gene (an inhibitor of a transcription factor that acts on HIV) and the immunoglobulin heavy chain genes. These markers will be analyzed in a cohort of HIV-infected individuals. Over 20 loci that represent expressed sequences have been mapped on chromosome 3, a chromosome involved in cytogenetic abnormalities in a number of malignancies. These expressed sequence markers will be employed in identifying putative tumor suppressor loci. A fine structure genetic map of the nevoid basal cell carcinoma syndrome region has been constructed.