17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

      Human genetics
      Base Sequence, DNA Primers, Female, Genes, Reporter, Genetic Variation, genetics, Genotype, Humans, Luciferases, metabolism, Male, Microsatellite Repeats, Molecular Sequence Data, Nerve Tissue Proteins, Neuroblastoma, Pedigree, Synucleins, Transfection, Tumor Cells, Cultured, alpha-Synuclein

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Comments

          Comment on this article