Document Detail

Functional analysis of intra-allelic variation at NACP-Rep1 in the alpha-synuclein gene.
MedLine Citation:
PMID:  12923682     Owner:  NLM     Status:  MEDLINE    
NACP-Rep1, a polymorphic microsatellite upstream of the alpha-synuclein gene ( SNCA), consisting of the nucleotides (TC)(x)(T)(2)(TC)(y)(TA)(z)(CA)(w), has five alleles originally defined by 2-bp differences in (CA)(w). Different NACP-Rep1 alleles have been associated with sporadic Parkinson's disease in some, but not all, studies and can effect expression driven by the SNCA promoter over a three-fold range in the neuroblastoma cell line, SH-SY5Y. By analyzing children in CEPH families in which parents appeared to be homozygous for a NACP-Rep1 allele, we found that there are sequence differences within same-sized NACP-Rep1 alleles, contributed mainly by variation of the (TC)(y)(TA)(z) portion of the microsatellite repeat. To test whether these sequence differences might impact on promoter function we determined the effect of two sequence variant alleles, both of size "1", using the luciferase reporter system. There was only a very small expression difference between these two variant alleles. This finding implies that the overall length of the NACP-Rep1 allele plays the main role in the transcription regulation by the NACP-Rep1 element and suggests that functional differences due to sequence heterogeneity within NACP-Rep1 alleles of the same length are probably not confounding factors in association studies based on alleles defined by length.
Ornit Chiba-Falek; Jeffrey W Touchman; Robert L Nussbaum
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-08-16
Journal Detail:
Title:  Human genetics     Volume:  113     ISSN:  0340-6717     ISO Abbreviation:  Hum. Genet.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-23     Completed Date:  2003-10-31     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  426-31     Citation Subset:  IM    
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Drive MSC 4472, Bethesda, Maryland 20892-4472, USA.
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MeSH Terms
Base Sequence
DNA Primers
Genes, Reporter
Genetic Variation / genetics*
Luciferases / genetics,  metabolism
Microsatellite Repeats / genetics
Molecular Sequence Data
Nerve Tissue Proteins / genetics*
Tumor Cells, Cultured
Reg. No./Substance:
0/DNA Primers; 0/Nerve Tissue Proteins; 0/SNCA protein, human; 0/Synucleins; 0/alpha-Synuclein; EC 1.13.12.-/Luciferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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