Analysis of the physiological and pathological function of DYT3, a multiple transcript system mutated in the X-linked dystonia parkinsonism syndrome (XDP)

X连锁肌张力障碍帕金森综合征（XDP）中突变的多转录系统DYT3的生理和病理功能分析

• 批准号: 5424970
• 负责人: Professor Dr. Ulrich Müller
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5424970?language=en
• 关键词: Analysis; physiological; pathological; function; DYT3

The X-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder characterized by distonia and parkinsonism. The disorder is genetically homogeneous and has been exclusively diagnosed in patients in Filipino descent. XDP is caused by one or more disease-specific single-nucleotide changes (DSCs) in a novel mulitple transcript system, DYT3, located in Xq13.1 DYT3 is composed of at least 16 exons and there is a minimum of three transcription start sites that encode four different transcripts. Two of these transcripts include distal portions of TAF1 (TATA-box binding protein - associated factor 1) and are alternatively spliced. There are 5 DSCs within DYT3 one of which lies within an exon utilized by all alternative transcripts. We will study both physiological and pathological function of DYT3 by 1) Complete analysis of all alternative transcripts of DYT3 and of their transcription start sites; 2) Quantification of alternative transcripts; 3) Investigation of possible translation of parts of DYT3; 4) Elucidation of the effects of DSCs on expression of other genes using Affymetrix expression arrays.

X连锁肌张力障碍-帕金森综合征（XDP）是一种严重的运动障碍，其特征是张力障碍和帕金森综合征。这种疾病在遗传上是同质的，并且只在菲律宾血统的患者中被诊断出来。XDP是由一个或多个疾病特异性的单核苷酸变化（DSC）引起的，位于Xq13.1的多转录系统DYT 3由至少16个外显子组成，至少有3个转录起始位点，编码4种不同的转录本。这些转录物中的两个包括TAF 1（TATA盒结合蛋白相关因子1）的远端部分，并且是可变剪接的。DYT 3内有5个DSC，其中一个位于所有替代转录物所利用的外显子内。我们将通过以下方式研究DYT 3的生理和病理功能：1）完整分析DYT 3的所有替代转录物及其转录起始位点; 2）定量替代转录物; 3）研究DYT 3部分的可能翻译; 4）使用Affyphase表达阵列阐明DSC对其他基因表达的影响。