ISOLATION OF THE GENE FOR CHEDIAK-HIGASHI SYNDROME

Chediak-Higashi综合征（CHS）是一种罕见的免疫缺陷病， 包括止血改变的临床表现， 恶性肿瘤，溶酶体功能异常，导致缺乏 “自然杀手”活动，以及特定子集的增加， T淋巴细胞导致这种综合症的基因还没有被发现。 在人或鼠系统中表征，尽管 小鼠类风湿综合征基因的染色体定位 (bg)已经被确认了 这个项目的目标是：1）生成一个小鼠“跳跃库”， 鉴定接近bg的新探针，2）定义限制性片段长度 多态性（RFLP）与这些探针通过交叉杂交， 人DNA，3）通过以下方法确定探针与CHS基因的遗传连锁： RFLP和家族分析，4）分析人和鼠的北方印迹， 鉴定推定基因的转录物，和5）对推定的CHS进行测序 基因并预测蛋白质产物。 本发明公开了一种基于“反向遗传学”鉴定基因的技术， 它的染色体定位是存在的，在这种情况下， 由于存在先前已经将该基因 映射。CHS基因的鉴定应提供以下信息： 止血、免疫监视、溶酶体功能和体内 γ δ T淋巴细胞的功能。 博士兰德尔·霍尔科姆正在完成医学专科的培训 并已经启动了一项富有成效的研究， 关于CHS的文章他在分子生物学方面 生物技术所需的成功完成， 在过去的两年里，这里描述的研究计划。部 大部分研究将在遗传学研究所进行， 重组DNA研究所需的设备，包括组织培养和 动物设施。血液科和遗传学系 赞助期刊俱乐部、实验室会议和几个系列讲座，以及 为研究提供了一个令人兴奋和刺激的环境。

Chediak-Higashi syndrome (CHS) is a rare immuno-deficiency disease with manifestations involving alterred hemostasis, an increase in the frequency of malignancies, abnormal function of lysosomes with resultant lack of "Natural Killer" activity, and an increase in a specific subset of T-lymphocytes. The gene responsible for the syndrome has not been characterized in either the human or murine system, although the chromosomal location of the gene causing the analogous syndrome in mice (bg) has been identified. The goals of this project are: 1) Generate a murine "jumping library" to identify new probes close to bg, 2) Define restriction fragment length polymorphisms (RFLP) with these probes through cross hybridization with human DNA, 3) Determine genetic linkage of the probes to the CHS gene by RFLP and family analysis, 4) analyze human and murine northern blots to identify transcripts of the putative gene and 5) sequence putative CHS genes and predict the protein product. The technology for identifying a gene by "reverse genetics" on the basis of its chromosomal location exists and should be facilitated in this instance by the presence of an animal model for which the gene has been previously mapped. Identification of the CHS gene should provide information about hemostasis, immune surveillance, lysosomal function, and the in vivo function of gamma delta T-lymphocytes. Dr. Randall Holcombe is completing training in the medical subspecialties of hematology and oncology and has already initiated a productive research program concerning CHS. He has developed expertise in the molecular biological techniques required for the successful completion of the research program described herein over the prior two years. The Department of Genetics, where the bulk of the research will be performed, has the equipment necessary for recombinant DNA research, with tissue culture and animal facilities. The Hematology Division and the Department of Genetics sponsor journal clubs, lab meetings, and several lecture series, and provide an exciting and stimulating environment for research.