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.

图雷特综合征是一种神经精神疾病，其特征是 存在多个不自主的运动和发声抽搐。 模式 这种疾病的遗传最符合常染色体显性模式。 尽管有大量的多个受影响成员的谱系， 与任何遗传标记的连锁已经被发现。 连锁分析表明，遗传机制导致的 疾病可能比最初预期的更复杂。 因此，在本发明中， 识别与妥瑞症有关的基因的替代方法 应考虑综合症。 先前已经描述了一个系谱，其中7;18平衡 易位是遗传在一个家庭与多个成员受到影响 患有妥瑞症 此外，具有缺失的患者 18q21.3-qter和Tourette综合征也有报道。 这些情况 表明与抽动秽语综合征病因有关的基因在 18 q，特别是在易位断裂点的位点。 血液 样本是从一个继承了 平衡易位和易位的位置 与18号染色体DNA标记的关系。 两种酵母 人工染色体已经通过荧光原位鉴定 跨越易位断裂点杂交。 这个提议描述了鉴定基因的实验方法 定位在易位断点上。 首先，一个克隆的粘粒 在易位断裂点上定位。 这个克隆的粘粒 然后将用于鉴定7号染色体和 染色体18起源，将用于识别基因，地图在 断点区 这些基因将被表征，以确定是否 它们的表达可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 确定它们作为抽动秽语综合征候选基因的潜力。