ISOLATION OF THE GENE FOR CHEDIAK-HIGASHI SYNDROME

Chediak-Higashi综合征(CHS)是一种罕见的免疫缺陷疾病，具有 涉及交替止血的表现，频率增加 在恶性肿瘤中，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。导致这种综合征的基因还没有 以人类或小鼠系统为特征，尽管 小鼠类似综合征致病基因的染色体定位 (BG)已确定。 这个项目的目标是：1)建立一个小鼠跳跃图书馆 识别BG附近的新探针，2)定义限制片段长度 通过与这些探针的交叉杂交，获得这些探针的多态性(RFLP) 人类DNA，3)通过以下方式确定探针与CHS基因的遗传连锁 RFLP和家系分析，4)分析人和小鼠的Northern blotting 鉴定推定基因的转录本和5)推定的CHS序列 基因和预测蛋白质产物。 基于基因识别的“反向遗传学”技术 它的染色体定位是存在的，在这种情况下应该加以便利。 通过一个动物模型的存在，该基因以前已经被用于 已映射。CHS基因的鉴定应提供有关 止血、免疫监测、溶酶体功能和体内 γ-βT淋巴细胞的功能。 兰德尔·霍尔科姆博士正在完成医学子专科的培训 在血液学和肿瘤学方面，他已经开始了一项富有成效的研究 有关社区卫生服务的计划。他已经发展出了分子方面的专业知识 成功完成这一任务所需的生物技术 在此描述的研究计划在前两年。该部门 遗传学的大部分研究将在那里进行，有 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 为研究提供一个令人兴奋和鼓舞人心的环境。

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.