CANDIDATE REGION FOR TOURETTE SYNDROME

多发性抽动症是一种神经精神障碍，其特点是 多发性的、不自主的运动和发声痉挛。一种新模式 这种疾病的遗传最符合常染色体显性遗传模式。 尽管有大量具有多个受影响成员的家系，但没有 已经发现了与任何遗传标记的关联。在以下方面缺乏成功 连锁分析表明，导致这一现象的遗传机制 混乱可能比最初预期的更复杂。因此， 识别抽动症相关基因的替代方法 应考虑综合征。 之前已经描述过一种谱系，其中7：18平衡 易位在一个有多个成员受影响的家庭中遗传 多发性抽动症。此外，一名基因缺失的患者 18q21.3-QTER和Tourette综合征也有报道。这些案件 提示Tourette综合征的病因学相关基因在 18q，特别是在易位断裂点的位置。一条血路 样本已从其中一名继承了 平衡易位与易位位置的尊重 对众多染色体的18个DNA标记已经确定。两个酵母 人工染色体已被荧光原位鉴定 跨越易位断点的杂交。 这项建议描述了识别基因的实验方法。 位于转位断点处的地图。首先，宇宙飞船的克隆人将是 确定了易位断点处的地图。这个宇宙体克隆人 用于鉴定7号染色体和7号染色体的其他克隆 18号染色体的起源，将被用来识别在 断点区域。这些基因的特征将决定是否 它们的表达可能会因易位的存在而改变。 它们的组织特异性表达模式将被表征为 确定它们作为Tourette综合征候选基因的潜力。

Tourette Syndrome is a neuropsychiatric disorder, the hallmark of which is the presence of multiple, involuntary motor and vocal tics. The mode of inheritance of this disorder best fits an autosomal dominant pattern. Despite the large number of pedigrees with multiple affected members, no linkage with any genetic marker has been found. The lack of success with linkage analysis suggests that the genetic mechanism leading to the disorder may be more complex than originally anticipated. Thus, alternative approaches to identifying a gene involved with Tourette syndrome should be considered. A pedigree has been previously described where a 7;18 balanced translocation was inherited in a family with multiple members affected with Tourette syndrome. In addition, a patient with a deletion of 18q21.3-qter and Tourette syndrome has also been reported. These cases suggest that a gene involved in the etiology of Tourette syndrome maps in 18q, specifically at the site of the translocation breakpoint. A blood sample has been obtained from one of the individuals inheriting the balanced translocation and the location of the translocation with respect to numerous chromosome 18 DNA markers has been determined. Two yeast artificial chromosomes have been identified by fluorescent in situ hybridization that span the translocation breakpoint. This proposal describes the experimental approach for identifying genes that map at the translocation breakpoint. First, a cosmid clone will be identified that maps at the translocation breakpoint. This cosmid clone will then be used to identify additional clones of both chromosome 7 and chromosome 18 origin that will be used to identify genes that map at the breakpoint region. The genes will be characterized to determine whether their expression could be altered by the presence of the translocation. Their tissue-specific expression pattern will be characterized to determine their potentials as a candidate gene for Tourette syndrome.