Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism
Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism
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DOI：
10.1086/512129
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发表时间：
2007-03-01
影响因子：
9.8
通讯作者：
Tamiya, Gen
中科院分区：
文献类型：
--
作者：
Makino, Satoshi;Kaji, Ryuji;Tamiya, Gen
X连锁肌张力障碍-帕金森综合征（XDP）是菲律宾特有的运动障碍。疾病基因座DYT 3已定位于Xq13.1。为了寻找致病基因，我们进行了基因组测序分析，然后对XDP脑组织进行了表达分析。我们在TATA结合蛋白相关因子1基因（TAF 1）的内含子中发现了疾病特异性SVA（（s）在bar下的散在核元件，（v）在bar下的可变数目的串联重复序列，和（A）在bar下的复合）反转录转座子插入，TAF 1编码TFIID复合物的最大组分，并显著降低尾状核中TAF 1和多巴胺受体D2基因（DRD 2）的表达水平。我们还确定了患者尾状核基因组中逆转录转座子的DNA甲基化异常模式，这可能是TAF 1表达降低的原因。我们的研究结果表明，TAF 1基因的神经元特异性表达减少与XDP有关。
X-linked dystonia- parkinsonism (XDP) is a movement disorder endemic to the Philippines. The disease locus, DYT3, has been mapped to Xq13.1. In a search for the causative gene, we performed genomic sequencing analysis, followed by expression analysis of XDP brain tissues. We found a disease- specific SVA ((s) under bar hort interspersed nuclear element, (v) under bar ariable number of tandem repeats, and (A) under bar lu composite) retrotransposon insertion in an intron of the TATA- binding protein-associated factor 1 gene (TAF1), which encodes the largest component of the TFIID complex, and significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus. We also identified an abnormal pattern of DNA methylation in the retrotransposon in the genome from the patient's caudate, which could account for decreased expression of TAF1. Our findings suggest that the reduced neuron-specific expression of the TAF1 gene is associated with XDP.