Characterization of the human α-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms¹

Article type: Research Article

Authors: Xia, Yu^a | Saitoh, Tsunao^{a; 5} | Uéda, Kenji^{a; c} | Tanaka, Seigo^{a; 2} | Chen, Xiaohua^a | Hashimoto, Makoto^a | Hsu, Leigh^a | Conrad, Chris^{a; 3} | Sundsmo, Mary^a | Yoshimoto, Makoto^{a; 4} | Thal, Leon^a | Katzman, Robert^a | Masliah, Eliezer^{a; b; *}

Affiliations: [a] Department of Neurosciences, University of California, San Diego, La Jolla, CA92093-0624, USA | [b] Department of Pathology, University of California, San Diego, La Jolla, CA92093-0624, USA | [c] Department of Neurochemistry, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya, Tokyo 156-8585, Japan

Correspondence: [*] Corresponding author: Dr. E. Masliah, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0624, USA. Tel.: +1 858 534 1376; Fax: +1 858 534 6232; E-mail: [email protected].

Note: [1] The sequences reported in this paper have been submitted to the GenBank database under the following accession numbers: U46896-U46901, AF041005-AF041007.

Note: [2] Current address: Institute for Chemical Research, University of Kyoto, Uji, Kyoto 611, Japan.

Note: [3] Current address: F526, Department of Pathology, Albert Einstein College of Medicine, Bronx, NY10461, USA.

Note: [4] Current address: Department of Molecular Biology, Taisho Pharmaceutical Co, Ltd, Omiya, Saitama 330, Japan.

Note: [5] Deceased.

Abstract: The human NACP/α-synuclein gene has been cloned. This gene consists of 6 exons ranging in size from 42 to 1110 bp. The translation start codon ATG is encoded by exon 2 and the stop codon TAA is encoded by exon 6. The non-Aβ component of Alzheimer's disease amyloid (NAC) is encoded by exon 4. The two previously reported minor isoforms of NACP/α-synuclein, NACP112 [29] and NACP126 [6], are alternatively spliced products, in which exon 5 and exon 3 are spliced out, respectively. Exon 1 was found to have different splicing sites, producing different 5'-untranslated sequences in the cDNAs. A previously reported dinucleotide repeat polymorphic marker has been mapped to 8kb upstream of the transcription start site. A highly TC-rich sequence in intron 4 was found to be polymorphic by length and four alleles, A0, A1, A2 and B have been identified in the Caucasian population. Genotyping this polymorphism among pure Alzheimer's, Lewy body variant and Parkinson's subjects and aged normal control subjects did not reveal any significant differences.

DOI: 10.3233/JAD-2001-3508

Journal: Journal of Alzheimer's Disease, vol. 3, no. 5, pp. 485-494, 2001