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)是一种以肌张力障碍和帕金森综合征为特征的严重运动障碍。这种疾病在基因上是同质的，只在菲律宾血统的患者中被诊断出来。XDP是由一个新的多重转录系统中的一个或多个疾病特异性单核苷酸改变(DSCs)引起的，DYT3位于Xq13.1，由至少16个外显子组成，至少有3个转录起始点，编码4个不同的转录本。其中两个转录本包括TAF1(TATA-box结合蛋白相关因子1)的远端部分，并进行选择性剪接。在DYT3中有5个DSC，其中一个位于所有可供选择的转录本利用的外显子中。我们将通过以下方式研究DYT3的生理和病理功能：1)完整分析DYT3的所有可选转录本及其转录起始点；2)可选转录本的量化；3)DYT3部分可能的翻译研究；4)利用Affymetrix表达阵列阐明DSCs对其他基因表达的影响。

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.