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.
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. Montesi, S. Sorbi, I. Rainero, L. Pinessi, R. J. Polinsky, P. Frommelt, R. Duara, R. Lopez, D. Pollen, J. F. Gusella, R. Tanzi, D. MacLachlan, D. Crapper, P. H. St George-Hyslop. - In: NEUROLOGY. - ISSN 0028-3878. - 43:11(1993 Nov), pp. 2275-9-2279.
|Titolo:||Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease|
|Parole Chiave:||Pedigree; Genetic Linkage; Promoter Regions, Genetic; Polymorphism, Genetic; Humans; Restriction Mapping; Alzheimer Disease; Adult; Middle Aged; Genes, fos; Chromosomes, Human, Pair 14; Amyloid beta-Protein Precursor|
|Settore Scientifico Disciplinare:||Settore MED/03 - Genetica Medica|
|Data di pubblicazione:||nov-1993|
|Appare nelle tipologie:||01 - Articolo su periodico|