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.
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.
Busby
Victoria
V
Department of Neuroscience, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom.
Goossens
Steven
S
Nowotny
Petra
P
Hamilton
Gillian
G
Smemo
Scott
S
Harold
Denise
D
Turic
Dragana
D
Jehu
Luke
L
Myers
Amanda
A
Womick
Meredith
M
Woo
Daniel
D
Compton
Danielle
D
Doil
Lisa M
LM
Tacey
Kristina M
KM
Lau
Kit F
KF
Al-Saraj
Safa
S
Killick
Richard
R
Pickering-Brown
Stuart
S
Moore
Pamela
P
Hollingworth
Paul
P
Archer
Nicola
N
Foy
Catherine
C
Walter
Sarah
S
Lendon
Corrine
C
Iwatsubo
Takeshi
T
Morris
John C
JC
Norton
Joanne
J
Mann
David
D
Janssens
Barbara
B
Hardy
John
J
O'Donovan
Michael
M
Jones
Lesley
L
Williams
Julie
J
Holmans
Peter
P
Owen
Michael J
MJ
Grupe
Andrew
A
Powell
John
J
van Hengel
Jolanda
J
Goate
Alison
A
Van Roy
Frans
F
Lovestone
Simon
S
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
D016229:Amyloid beta-Peptides; C441963:CTNNA3 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051178:alpha Catenin