Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial alzheimer's disease

E. I. Rogaev, W. J. Lukiw, G. Vaula, J. L. Haines, E. A. Rogaeva, T. Tsuda, N. Alexandrova, Y. Liang, M. Mortilla, L. Amaducci, L. Bergamini, A. C. Bruni, J. F. Foncin, F. Macciardi, M. P. Montesi, S. Sorbi, I. Rainero, L. Pinessi, R. J. Polinsky, P. FrommeltR. Duara, R. Lopez, D. Pollen, J. F. Gusella, R. Tanzi, D. Crapper Maclachlan, P. H. St. George-Hyslop

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5′ APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD. A conservative third-position T→C mutation was demonstrated in exon 2 (codon 84) of c-FOS, and a C→G substitution was detected at -209 bp in the 5′ promoter of APP. Neither were unique to FAD and are unlikely to be pathogenic or secondary modifiers of the FAD phenotype. We conclude that the c-FOS open reading frame is probably not the site of the FAD14 locus, but we cannot exclude the existence of modifier loci on chromosome 21.

Original languageEnglish (US)
Pages (from-to)2275-2279
Number of pages5
JournalNeurology
Volume43
Issue number11
DOIs
StatePublished - Nov 1993

ASJC Scopus subject areas

  • Clinical Neurology

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    Rogaev, E. I., Lukiw, W. J., Vaula, G., Haines, J. L., Rogaeva, E. A., Tsuda, T., Alexandrova, N., Liang, Y., Mortilla, M., Amaducci, L., Bergamini, L., Bruni, A. C., Foncin, J. F., Macciardi, F., Montesi, M. P., Sorbi, S., Rainero, I., Pinessi, L., Polinsky, R. J., ... St. George-Hyslop, P. H. (1993). Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial alzheimer's disease. Neurology, 43(11), 2275-2279. https://doi.org/10.1212/wnl.43.11.2275