A genomic sequence analysis of the mouse and human microtubule-associated protein tau

Microtubule associated protein tau (MAPT) encodes the microtubule associate d protein tau, the primary component of neurofibrillary tangles found in Al zheimer's disease and other neurodegenerative disorders. Mutations in the c oding and intronic sequences of MAPT cause autosomal dominant frontotempora l dementia (FTDP-17). MAPT is also a candidate gene for progressive supranu clear palsy and hereditary dysphagic dementia. A human PAC (201 kb) and a m ouse BAC (161 kb) containing the entire MAPT and Mtapt genes, respectively, were identified and sequenced. Comparative DNA sequence analysis revealed over 100 conserved non-repeat potential cis-acting regulatory sequences in or close to MAPT. Those islands with greater than 67% nucleotide identity r ange in size from 20 to greater than 1700 nucleotides. Over 90 single nucle otide, polymorphisms were identified in MAPT that are candidate susceptibil ity alleles for neurodegenerative disease. The 5' and 3' flanking genes for MAPT are the corticotrophin-releasing factor receptor (CRFR) gene and KIAA 1267, a gene of unknown function expressed in brain.