MOLECULAR STUDIES IN TUBEROUS SCLEROSIS

结节性硬化症(TSC)是一种常染色体显性遗传病 影响许多器官系统的高突变率。TS是 以错构瘤和Harmartias为特征，症状可从 良性皮肤斑点至智力低下伴癫痫至早产儿 死亡。估计TSC的患病率为每10,000人中有1人。TSC是一种 异质性障碍。1987年，发现了两个人之间的遗传连锁 TSC和染色体9q34上的ABO血型。大约三分之一 的家系似乎与9q基因座相关联。最近，这就是 实验室使用了明显与9q基因座无关的家族，结果显示 位于染色体16p13的D16S283标记与 一大群台糖家族。 分离9q34 TSC基因的进展相对缓慢 主要是因为家庭的异质性。最近发现了一种 位于16p13的第二个TSC基因座，包括TSC的大部分 允许澄清这些问题，并应在很大程度上 加快分离9q TSC基因的进展。 虽然TSC在六年前首次与9Q联系在一起，但可以说的是 直到最近，这种疾病的病位分布在大约 在9q34的D9S125远端20厘米。然而，最近的分析已经本地化了。 9号染色体的TSC基因座位于大约2 cM的侧翼区域 近端为胸径，远端为D9S114。努力进一步完善 目前正在通过开发新的标记进行TSC基因座的定位。 分离出9号染色体TSC区的近侧翼标记 可使用脉冲场电泳法和人工酵母菌作图 染色体(Yac)S从新的CEPH兆数据库文库中分离出来 现有的YAC库。将使用以下方法物理克隆TSC区域 YAC和一个围绕TSC轨迹的宇宙重叠群。新的标记将 将分离包含在该区域内的基因，并 被检测为TSC候选基因。

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with a high mutation rate which affects numerous organ systems. TS is characterized by hamartomas and harmartias and symptoms can vary from benign skin macules to mental retardation with epilepsy to premature death. The estimated prevalence of TSC is 1 per 10,000. TSC is a heterogeneous disorder. In 1987 genetic linkage was demonstrated between TSC and the ABO blood group on chromosome 9q34. Approximately one third of TSC families seem to be linked to the 9q loci. More recently this laboratory, using families clearly unlinked to the 9q loci, has shown linkage between the D16S283 marker, located at chromosome 16p13, and a large group of TSC families. Progress in isolating the 9q34 TSC gene has proceeded relatively slowly primarily because of family heterogeneity. Recent identification of a second TSC loci at 16p13, which includes the majority of the TSC families, allows the clarification of these issues and should greatly accelerate progress in isolating the 9q TSC gene. Although TSC was first linked to 9q six years ago all that could be said until recently is that the disease loci lay in a region of approximately 20 cM distal to D9S125 in 9q34. Recent analyses have, however, localized the chromosome 9 TSC loci to a region of approximately 2 cM flanked proximally by DBH and distally by D9S114. Efforts to further refine the TSC loci by developing new markers are presently underway. With the isolation of close flanking markers the chromosome 9 TSC region may be mapped using pulse field electrophoresis and Yeast Artificial Chromosomes (YAC)'s isolated from the new CEPH megabase library and existing YAC libraries. The TSC region will be physically clone using Yacs and a cosmic contig encompassing the TSC locus. New markers will be generated, genes contained within the region will be isolated and tested as TSC candidate genes.