Caffrey TM, Joachim C, Paracchini S, Esiri MM, Wade-Martins R.
Haplotype-specific expression of exon 10 at the human MAPT locus.
Hum Mol Genet. 2006 Dec 15;15(24):3529-37.
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This paper by Caffrey and colleagues suggests that the H1 association between tau and progressive supranuclear palsy (PSP, and possibly with AD, too) is driven by the fact that the H1 allele expresses higher levels of the four-repeat tau transcript relative to the H2 allele. However, as we and Rademakers have shown, the PSP association is not simply with H1, but with a variant of this haplotype which we have named H1c. In a paper in press (which should be online in Neurobiology of Disease this month: Myers et al.: The MAPT H1c risk haplotype is associated withe increased expression especially of 4 repeat containing transcripts), we have shown that only the H1c haplotype is associated with this higher level of four-repeat transcript, and we confirm that this same haplotype has an association with Alzheimer disease.
Myers AJ, Kaleem M, Marlowe L, Pittman AM, Lees AJ, Fung HC, Duckworth J, Leung D, Gibson A, Morris CM, de Silva R, Hardy J.
The H1c haplotype at the MAPT locus is associated with Alzheimer's disease.
Hum Mol Genet. 2005 Aug 15;14(16):2399-404.
Pittman AM, Myers AJ, Abou-Sleiman P, Fung HC, Kaleem M, Marlowe L, Duckworth J, Leung D, Williams D, Kilford L, Thomas N, Morris CM, Dickson D, Wood NW, Hardy J, Lees AJ, de Silva R.
Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration.
J Med Genet. 2005 Nov;42(11):837-46.
Rademakers R, Melquist S, Cruts M, Theuns J, Del-Favero J, Poorkaj P, Baker M, Sleegers K, Crook R, De Pooter T, Bel Kacem S, Adamson J, Van den Bossche D, Van den Broeck M, Gass J, Corsmit E, de Rijk P, Thomas N, Engelborghs S, Heckman M, Litvan I, Crook J, De Deyn PP, Dickson D, Schellenberg GD, Van Broeckhoven C, Hutton ML.
High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy.
Hum Mol Genet. 2005 Nov 1;14(21):3281-92.