title: Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.
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.
authors.affiliation: Division of Neurology, University of Toronto, Ontario, Canada.
authors.forename: E I
authors.initials: EI
authors.lastname: Rogaev
authors.forename: W J
authors.initials: WJ
authors.lastname: Lukiw
authors.forename: G
authors.initials: G
authors.lastname: Vaula
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: E A
authors.initials: EA
authors.lastname: Rogaeva
authors.forename: T
authors.initials: T
authors.lastname: Tsuda
authors.forename: N
authors.initials: N
authors.lastname: Alexandrova
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: M
authors.initials: M
authors.lastname: Mortilla
authors.forename: L
authors.initials: L
authors.lastname: Amaducci
authors.forename: L
authors.initials: L
authors.lastname: Bergamini
authors.forename: A C
authors.initials: AC
authors.lastname: Bruni
authors.forename: J F
authors.initials: JF
authors.lastname: Foncin
authors.forename: F
authors.initials: F
authors.lastname: Macciardi
authors.forename: M
authors.initials: M
authors.lastname: Montesi
authors.forename: S
authors.initials: S
authors.lastname: Sorbi
authors.forename: I
authors.initials: I
authors.lastname: Rainero
authors.forename: L
authors.initials: L
authors.lastname: Pinessi
authors.forename: R J
authors.initials: RJ
authors.lastname: Polinsky
authors.forename: P
authors.initials: P
authors.lastname: Frommelt
authors.forename: R
authors.initials: R
authors.lastname: Duara
authors.forename: R
authors.initials: R
authors.lastname: Lopez
authors.forename: D
authors.initials: D
authors.lastname: Pollen
authors.forename: J F
authors.initials: JF
authors.lastname: Gusella
authors.forename: R
authors.initials: R
authors.lastname: Tanzi
authors.forename: D
authors.initials: D
authors.lastname: MacLachlan
authors.forename: D
authors.initials: D
authors.lastname: Crapper
authors.forename: P H
authors.initials: PH
authors.lastname: St George-Hyslop
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D016762:Genes, fos / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D016564:Amyloid beta-Protein Precursor