title: Alpha-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer's disease.
abstract: The gene encoding alpha-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that alpha-T-catenin is expressed in human brain, and like other alpha-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Abeta deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n > 700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10.
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom.
authors.forename: Victoria
authors.initials: V
authors.lastname: Busby
authors.forename: Steven
authors.initials: S
authors.lastname: Goossens
authors.forename: Petra
authors.initials: P
authors.lastname: Nowotny
authors.forename: Gillian
authors.initials: G
authors.lastname: Hamilton
authors.forename: Scott
authors.initials: S
authors.lastname: Smemo
authors.forename: Denise
authors.initials: D
authors.lastname: Harold
authors.forename: Dragana
authors.initials: D
authors.lastname: Turic
authors.forename: Luke
authors.initials: L
authors.lastname: Jehu
authors.forename: Amanda
authors.initials: A
authors.lastname: Myers
authors.forename: Meredith
authors.initials: M
authors.lastname: Womick
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.forename: Danielle
authors.initials: D
authors.lastname: Compton
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Doil
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Tacey
authors.forename: Kit F
authors.initials: KF
authors.lastname: Lau
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Saraj
authors.forename: Richard
authors.initials: R
authors.lastname: Killick
authors.forename: Stuart
authors.initials: S
authors.lastname: Pickering-Brown
authors.forename: Pamela
authors.initials: P
authors.lastname: Moore
authors.forename: Paul
authors.initials: P
authors.lastname: Hollingworth
authors.forename: Nicola
authors.initials: N
authors.lastname: Archer
authors.forename: Catherine
authors.initials: C
authors.lastname: Foy
authors.forename: Sarah
authors.initials: S
authors.lastname: Walter
authors.forename: Corrine
authors.initials: C
authors.lastname: Lendon
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Joanne
authors.initials: J
authors.lastname: Norton
authors.forename: David
authors.initials: D
authors.lastname: Mann
authors.forename: Barbara
authors.initials: B
authors.lastname: Janssens
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Michael
authors.initials: M
authors.lastname: O'Donovan
authors.forename: Lesley
authors.initials: L
authors.lastname: Jones
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Peter
authors.initials: P
authors.lastname: Holmans
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Andrew
authors.initials: A
authors.lastname: Grupe
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.forename: Jolanda
authors.initials: J
authors.lastname: van Hengel
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Frans
authors.initials: F
authors.lastname: Van Roy
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D016022:Case-Control Studies; D002460:Cell Line; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D011110:Polymorphism, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins; D051178:alpha Catenin
chemical_list: D016229:Amyloid beta-Peptides; C441963:CTNNA3 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051178:alpha Catenin