CANDIDATE REGION FOR TOURETTE SYNDROME

抽动秽语综合征的候选区域

• 批准号: 2254371
• 负责人: JOAN M OVERHAUSER
• 金额: $ 10.58万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2254371
• 关键词: Tourette's syndrome; artificial chromosomes; chromosome translocation; complementary DNA; family genetics; gene deletion mutation; gene expression; genetic library; genetic mapping; human genetic material tag; molecular cloning; nucleic acid sequence; plasmids

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.

图雷特综合症是一种神经精神疾病，其标志是 有多种非自愿运动和声音的存在。 模式 这种疾病的遗传最适合常染色体显性模式。 尽管大量的血统书有多个受影响的成员，否 已经发现与任何遗传标记的联系。 缺乏成功 连锁分析表明，导致的遗传机制 疾病可能比最初预期的要复杂。 因此， 识别与图雷特有关的基因的替代方法 应考虑综合征。 先前已经描述了一个血统，其中7; 18平衡 易位是在一个家庭中继承的，有多个成员 与图雷特综合征。 另外，有删除的患者 18Q21.3-QTER和TOURETTE综合征也有报道。 这些情况 提出参与图雷特综合征图的病因中的基因 18q，特别是在易位断点的地点。 血液 样本是从继承的个人之一获得的 平衡的易位和易位的位置 已经确定了许多18个DNA标记的染色体。 两个酵母 人工染色体已通过荧光原位鉴定 跨越易位断点的杂交。 该建议描述了识别基因的实验方法 该地图处的易位断点。 首先，宇宙克隆将是 确定了易位断点处的地图。 这个宇宙克隆 然后将用于识别染色体7和 染色体18起源将用于识别在地图 断点区域。 这些基因将被表征以确定是否 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描述为 确定他们作为Tourette综合征候选基因的潜力。