MOLECULAR GENETICS OF NEUROFIBROMATOSIS TYPE 1

神经纤维瘤病1型(NF1)是一种常见的常染色体显性遗传病 有显著的临床发病率。NF1的遗传缺陷尚不清楚 人们对导致这种疾病的潜在病理生理学知之甚少 临床表现多样。 NF1基因的鉴定、分离和鉴定 对于进一步研究这一高度的病理生理学 多效性条件。NF1基因已被定位在q11.2带上 17号染色体和NF1基因座已经通过将两个 平衡易位是导致NF1疾病的原因。物理 地图研究已经定义了相距约60kb的断点，因此 物理上定义了一个可能包含NF1基因的区域。克隆的， 物理绘制的包含NF1基因座的基因组DNA使我们能够 确定该区域的活性转录本将用作探针 目的：寻找NF1患者基因组DNA重排。一块NF1的电池 在一个特定候选基因座附近的重排将识别 NF1基因。如果NF1基因被鉴定，NF1的cDNA将被 对NF1的基因组序列和突变等位基因进行测序和定位 个体将在DNA序列水平上进行表征。互补性 DNA序列将被用来表征NF1基因在 神经冠来源的组织。圆满完成这些具体目标 将为临床诊断和预后咨询提供试剂 NF1个人。NF1基因的特征也可能提供 对发育调控基因表达过程的洞察 神经脊源性组织和肿瘤进展-- 相关的显性遗传病。 David Viskochil是一名博士，医学博士，正在完成遗传学团契培训 在犹他大学与约翰·凯里博士和雷·怀特博士合作的项目。 他将90%的训练精力投入到绘制NF1赛道的地图上 由雷·怀特指导并由 霍华德·休斯医学院。Viskochil博士计划继续工作 冬虫夏草后NF1基因的分离与鉴定 安大略省大学儿科教研室教师聘任 犹他州在1990年7月。他将隶属于人力资源部 他将以一种综合的方式进行所有的研究 由霍华德·休斯医学研究所支持的NF1核心研究小组。

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder that has significant clinical morbidity. The genetic defect in NF1 is not known and little is understood of the underlying pathophysiology leading to the various clinical manifestations. The identification, isolation and characterization of the NF1 gene is paramount for further studies on the pathophysiology of this highly pleiotropic condition. The NF1 gene has been mapped to band q11.2 on chromosome 17 and the NF1 locus has been further defined by mapping two balanced translocations responsible for the NF1 condition. Physical mapping studies have defined breakpoints approximately 60-kb apart, thus physically defining a region likely to encompass the NF1 gene. Cloned, physically mapped genomic DNA encompassing the NF1 locus enables on to identify active transcripts from this region which will be used as probes to search for rearrangements in NF1 patient genomic DNA. A battery of NF1 rearrangements near one specific candidate gene locus would identify the NF1 gene. Providing the NF1 gene is identified, NF1 cDNAs will be sequenced and mapped to the genomic sequence and mutant alleles from NF1 individuals will be characterized at the DNA sequence level. Complementary DNA sequence will be used to characterize expression of the NF1 gene in neural crest-derived tissue. Successful completion of these specific aims will provide reagents for clinical diagnosis and prognosis counseling for NF1 individuals. The characterization of the NF1 gene may also provide insight into the processes of developmentally regulated gene expression in neural crest-derived tissue, and tumor progression in a neoplasia- associated dominant genetic disorder. David Viskochil is a Ph.D., M.D. completing a genetics fellowship training program with Dr. John Carey and Dr. Ray White at the University of Utah. He has devoted 90% of his training effort to mapping the NF1 locus as part of an NF1 research project directed by Ray White and supported by the Howard Hughes Medical Institute. Dr. Viskochil plans to continue working on the isolation and characterization of the NF1 gene after beginning a faculty appointment in the Department of Pediatrics at the University of Utah in July 1990. He will be affiliated with the Division of Human Genetics and he will conduct all research in an integrated fashion with the core NF1 research group supported by the Howard Hughes Medical Institute.