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Vol. 11, Issue 1, 78-86, January 2001

LETTER
Human and Mouse alpha -Synuclein Genes: Comparative Genomic Sequence Analysis and Identification of a Novel Gene Regulatory Element

Jeffrey W. Touchman,1 Anindya Dehejia,2 Ornit Chiba-Falek,3 Deborah E. Cabin,3 Jody R. Schwartz,4 Bonnie M. Orrison,3 Mihael H. Polymeropoulos,2 and Robert L. Nussbaum3,5

1 NIH Intramural Sequencing Center, National Institutes of Health, Gaithersburg, Maryland 20877, USA; 2 Novartis Pharmaceuticals, Gaithersburg, Maryland 20878, USA; 3 Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; 4 Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA

The human alpha -synuclein gene (SNCA) encodes a presynaptic nerve terminal protein that was originally identified as a precursor of the non-beta -amyloid component of Alzheimer's disease plaques. More recently, mutations in SNCA have been identified in some cases of familial Parkinson's disease, presenting numerous new areas of investigation for this important disease. Molecular studies would benefit from detailed information about the long-range sequence context of SNCA. To that end, we have established the complete genomic sequence of the chromosomal regions containing the human and mouse alpha -synuclein genes, with the objective of using the resulting sequence information to identify conserved regions of biological importance through comparative sequence analysis. These efforts have yielded ~146 and ~119 kb of high-accuracy human and mouse genomic sequence, respectively, revealing the precise genetic architecture of the alpha -synuclein gene in both species. A simple repeat element upstream of SNCA/Snca has been identified and shown to be necessary for normal expression in transient transfection assays using a luciferase reporter construct. Together, these studies provide valuable data that should facilitate more detailed analysis of this medically important gene.

[The genomic DNA sequence data described in this paper have been submitted to GenBank under accession nos. AF163864 (human) and AF163865 (mouse).]

5 Corresponding author.

11:78-86 ©2001 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/01 $5.00
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