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Author Notes:

Corresponding author: Andrew Escayg, Ph.D., Emory University, Department of Human Genetics, 615 Michael Street, Whitehead Building, Suite 301, Atlanta, Georgia 30322, Telephone number (404) 712-8328, Fax number (404) 727-3949, E-mail: aescayg@genetics.emory.edu

We thank Cheryl Strauss (Emory University), James Thomas (Emory University), Tamara Caspary (Emory University), and Michael Zwick (Emory University) for critically reading the manuscript.

We also thank Howard Rees (Emory University) for his help with the dissection of mouse brain regions.

Subjects:

Research Funding:

This work was supported by NIH Research Grant NS051834 (A.E.).

Keywords:

  • epilepsy
  • sodium channel
  • SCN1A
  • SCN2A
  • SCN3A
  • 5′ untranslated region
  • sequence alignment
  • conserved sequence
  • gene expression regulation

Characterization of 5? untranslated regions of the voltage-gated sodium channels SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences

Tools:

Journal Title:

Genomics

Volume:

Volume 90, Number 2

Publisher:

, Pages 225-235

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The human voltage-gated sodium channel gene cluster on chromosome 2q24 contains three paralogs, SCN1A, SCN2A, and SCN3A, which are expressed in the central nervous system. Mutations in SCN1A and SCN2A cause several subtypes of idiopathic epilepsy. Furthermore, many SCN1A mutations are predicted to reduce protein levels, emphasizing the importance of precise sodium channel gene regulation. To investigate the genetic factors that regulate the expression of SCN1A, SCN2A, and SCN3A, we characterized the 5′ untranslated region of each gene. We identified multiple noncoding exons and observed brain region differences in the expression level of noncoding exons. Comparative sequence analysis revealed 33 conserved noncoding sequences (CNSs) between the orthologous mammalian genes, and six CNSs between the three human paralogs. Seven CNSs corresponded to noncoding exons. Twelve CNSs were evaluated for their ability to alter the transcription of a luciferase reporter gene, and three resulted in a modest, but statistically significant change.

Copyright information:

© 2007 Elsevier Inc. All rights reserved.

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