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; Maria Daisy Tabuena; Elma Maranon; Marita Dantes; Lillian V Lee; Kazumasa Ogasawara; Ikuo Tooyama; Hiroyasu Akatsu; Masataka Nishimura; Gen Tamiya

doi:10.1086/512129

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

Am J Hum Genet. 2007 Mar;80(3):393-406. doi: 10.1086/512129. Epub 2007 Jan 23.

Authors

Satoshi Makino¹, Ryuji Kaji, Satoshi Ando, Maiko Tomizawa, Katsuhito Yasuno, Satoshi Goto, Shinnichi Matsumoto, Maria Daisy Tabuena, Elma Maranon, Marita Dantes, Lillian V Lee, Kazumasa Ogasawara, Ikuo Tooyama, Hiroyasu Akatsu, Masataka Nishimura, Gen Tamiya

Affiliation

¹ Department of Neurology and Neuroscience, University of Tokushima Graduate School of Medicine, Tokushima, Japan.

PMID: 17273961
PMCID: PMC1821114
DOI: 10.1086/512129

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alu Elements / genetics
Blotting, Northern
Case-Control Studies
Chromosomes, Human, X / genetics*
DNA / genetics
Down-Regulation
Dystonia / genetics*
Dystonia / pathology
Female
Genes, X-Linked
Genetic Diseases, X-Linked / genetics*
Genetic Diseases, X-Linked / pathology
Histone Acetyltransferases
Humans
Immunoenzyme Techniques
Male
Middle Aged
Molecular Sequence Data
Neurons / metabolism*
Neurons / pathology
Parkinsonian Disorders / genetics*
Parkinsonian Disorders / pathology
Pedigree
RNA, Messenger / genetics
RNA, Messenger / metabolism
Repetitive Sequences, Nucleic Acid / genetics
Reverse Transcriptase Polymerase Chain Reaction
TATA Box
TATA-Binding Protein Associated Factors / genetics*
Tandem Repeat Sequences / genetics
Transcription Factor TFIID / genetics*

Substances

RNA, Messenger
TATA-Binding Protein Associated Factors
Transcription Factor TFIID
DNA
Histone Acetyltransferases
TATA-binding protein associated factor 250 kDa

Associated data

GENBANK/AB191243