title: Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease.
abstract: Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred in conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3.
authors.affiliation: Department of Medicine (Neurology), University of Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Sherrington
authors.forename: E I
authors.initials: EI
authors.lastname: Rogaev
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: E A
authors.initials: EA
authors.lastname: Rogaeva
authors.forename: G
authors.initials: G
authors.lastname: Levesque
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Chi
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Holman
authors.forename: T
authors.initials: T
authors.lastname: Tsuda
authors.forename: L
authors.initials: L
authors.lastname: Mar
authors.forename: J F
authors.initials: JF
authors.lastname: Foncin
authors.forename: A C
authors.initials: AC
authors.lastname: Bruni
authors.forename: M P
authors.initials: MP
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: L
authors.initials: L
authors.lastname: Nee
authors.forename: I
authors.initials: I
authors.lastname: Chumakov
authors.forename: D
authors.initials: D
authors.lastname: Pollen
authors.forename: A
authors.initials: A
authors.lastname: Brookes
authors.forename: P
authors.initials: P
authors.lastname: Sanseau
authors.forename: R J
authors.initials: RJ
authors.lastname: Polinsky
authors.forename: W
authors.initials: W
authors.lastname: Wasco
authors.forename: H A
authors.initials: HA
authors.lastname: Da Silva
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: M A
authors.initials: MA
authors.lastname: Perkicak-Vance
authors.forename: R E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: P E
authors.initials: PE
authors.lastname: Fraser
authors.forename: J M
authors.initials: JM
authors.lastname: Rommens
authors.forename: P H
authors.initials: PH
authors.lastname: St George-Hyslop
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010375:Pedigree; D053764:Presenilin-1; D017433:Protein Structure, Secondary; D014158:Transcription, Genetic
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1