Human Genetics

, Volume 113, Issue 5, pp 426–431

Functional analysis of intra-allelic variation at NACP-Rep1 in the α-synuclein gene

  • Ornit Chiba-Falek
  • Jeffrey W. Touchman
  • Robert L. Nussbaum
Original Investigation

DOI: 10.1007/s00439-003-1002-9

Cite this article as:
Chiba-Falek, O., Touchman, J.W. & Nussbaum, R.L. Hum Genet (2003) 113: 426. doi:10.1007/s00439-003-1002-9


NACP-Rep1, a polymorphic microsatellite upstream of the α-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.

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Ornit Chiba-Falek
    • 1
  • Jeffrey W. Touchman
    • 2
    • 3
    • 4
  • Robert L. Nussbaum
    • 1
  1. 1.Genetic Disease Research BranchNational Human Genome Research Institute, National Institutes of HealthBethesdaUSA
  2. 2.NIH Intramural Sequencing CenterNational Institutes of HealthGaithersburgUSA
  3. 3.Pathogen Genomics DivisionThe Translational Genomics Research InstitutePhoenixUSA
  4. 4.School of Life SciencesArizona State UniversityTempeUSA