Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.
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.
Rogaev
E I
EI
Division of Neurology, University of Toronto, Ontario, Canada.
Lukiw
W J
WJ
Vaula
G
G
Haines
J L
JL
Rogaeva
E A
EA
Tsuda
T
T
Alexandrova
N
N
Liang
Y
Y
Mortilla
M
M
Amaducci
L
L
Bergamini
L
L
Bruni
A C
AC
Foncin
J F
JF
Macciardi
F
F
Montesi
M
M
Sorbi
S
S
Rainero
I
I
Pinessi
L
L
Polinsky
R J
RJ
Frommelt
P
P
Duara
R
R
Lopez
R
R
Pollen
D
D
Gusella
J F
JF
Tanzi
R
R
MacLachlan
D
D
Crapper
D
D
St George-Hyslop
P H
PH
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
D016564:Amyloid beta-Protein Precursor