title: Untangling the tau gene association with neurodegenerative disorders.
abstract: Pathological tau protein inclusions have long been recognized to define the diverse range of neurodegenerative disorders called the tauopathies, which include Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration. Mutations in the tau gene, MAPT, cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), and common variation in MAPT is strongly associated with the risk of PSP, corticobasal degeneration and, to a lesser extent, AD and Parkinson's disease (PD), implicating the involvement of tau in common neurodegenerative pathway(s). This review will discuss recent work towards the unravelling of the functional basis of this MAPT gene association. The region of chromosome 17q21 containing MAPT locus is characterized by the complex genomic architecture, including a large inversion that leads to a bipartite haplotype architecture, an inversion-mediated deletion and multiplications resulting from non-allelic homologous recombination between the MAPT family of low-copy repeats.
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, University College London, 1, Wakefield Street, London WC1N 1PJ, UK.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Pittman
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003704:Dementia / Q000235:genetics; D006239:Haplotypes; D020271:Heredodegenerative Disorders, Nervous System / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000235:genetics; D024801:Tauopathies / Q000235:genetics; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D012313:RNA