α-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
| Autor: | Peter Holmans, Joanne Norton, John Hardy, Kit Lau, Jolanda van Hengel, Gillian Hamilton, Pamela Moore, Luke Jehu, C. Lendon, Andrew Grupe, Sarah Walter, Kristina Tacey, Stuart Pickering-Brown, Takeshi Iwatsubo, Daniel Woo, Richard Killick, Meredith Womick, John Powell, Victoria L. Busby, Paul Hollingworth, Denise Harold, Danielle Compton, Petra Nowotny, Alison Goate, Lisa Doil, Barbara Janssens, David M. A. Mann, John C. Morris, Frans van Roy, Amanda J. Myers, Lesley Jones, Safa Al-Saraj, Michael John Owen, Simon Lovestone, Nicola Archer, Catherine Foy, Michael Conlon O'Donovan, Scott Smemo, Julie Williams, Steven Goossens, D. Turic |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Apolipoprotein E Beta-catenin Genotype Genetic Linkage DNA Mutational Analysis Gene Expression Single-nucleotide polymorphism Locus (genetics) Biology Cell Line Mice Cellular and Molecular Neuroscience Gene Frequency Alzheimer Disease Proto-Oncogene Proteins Animals Humans SNP Genetic Testing Allele Gene Aged Aged 80 and over Brain Chemistry Genetics Amyloid beta-Peptides Polymorphism Genetic Chromosomes Human Pair 10 Wnt signaling pathway Brain Chromosome Mapping Molecular biology Wnt Proteins Alternative Splicing Cytoskeletal Proteins Neurology Case-Control Studies biology.protein Molecular Medicine Female alpha Catenin Signal Transduction |
| Zdroj: | NeuroMolecular Medicine. 5:133-146 |
| ISSN: | 1535-1084 |
| DOI: | 10.1385/nmm:5:2:133 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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