Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism

Satoshi Makino, Ryuji Kaji, Satoshi Ando, Maiko Tomizawa, Katsuhito Yasuno, Satoshi Goto, Shinnichi Matsumoto, Ma Daisy Tabuena, Elma Maranon, Marita Dantes, Lillian V. Lee, Kazumasa Ogasawara, Ikuo Tooyama, Hiroyasu Akatsu, Masataka Nishimura, Gen Tamiya

Research output: Contribution to journalArticlepeer-review

152 Citations (Scopus)

Abstract

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 (short interspersed nuclear element, variable number of tandem repeats, and Alu 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.

Original languageEnglish
Pages (from-to)393-406
Number of pages14
JournalAmerican Journal of Human Genetics
Volume80
Issue number3
DOIs
Publication statusPublished - 2007 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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