Related Experiment Videos
A genomic sequence analysis of the mouse and human microtubule-associated protein tau
1Geriatric Research Education Clinical Center 182-B, Veterans Affairs Puget Sound Health Care System, Seattle Division, 1660 S. Columbian Way, Seattle, Washington 98108, USA.
Abstract:
Microtubule associated protein tau (MAPT) encodes the microtubule associated protein tau, the primary component of neurofibrillary tangles found in Alzheimer's disease and other neurodegenerative disorders. Mutations in the coding and intronic sequences of MAPT cause autosomal dominant frontotemporal dementia (FTDP-17). MAPT is also a candidate gene for progressive supranuclear palsy and hereditary dysphagic dementia. A human PAC (201 kb) and a mouse 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 range in size from 20 to greater than 1700 nucleotides. Over 90 single nucleotide polymorphisms were identified in MAPT that are candidate susceptibility alleles for neurodegenerative disease. The 5' and 3' flanking genes for MAPT are the corticotrophin-releasing factor receptor (CRFR) gene and KIAA1267, a gene of unknown function expressed in brain.
Insights
The microtubule-associated protein tau (MAPT) gene is crucial in neurodegenerative diseases like Alzheimer's. Sequencing identified regulatory elements and SNPs in MAPT, offering insights into disease susceptibility.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Microtubule-associated protein tau (MAPT) is a key component of neurofibrillary tangles in Alzheimer's disease.
- MAPT mutations are linked to autosomal dominant frontotemporal dementia (FTDP-17) and other neurodegenerative disorders.
Purpose of the Study:
- To identify and characterize regulatory sequences and genetic variations within the MAPT gene.
- To investigate the potential role of MAPT and its regulatory elements in neurodegenerative diseases.
Main Methods:
- Sequencing of human PAC and mouse BAC clones containing the MAPT and Mtapt genes.
- Comparative DNA sequence analysis to identify conserved non-repeat regulatory elements.
- Identification and analysis of single nucleotide polymorphisms (SNPs) within the MAPT gene.
Main Results:
- Over 100 conserved cis-acting regulatory sequences were identified in or near MAPT.
- Conserved regulatory islands varied in size from 20 to over 1700 nucleotides.
- More than 90 single nucleotide polymorphisms (SNPs) were found in MAPT, representing potential susceptibility alleles for neurodegenerative diseases.
Conclusions:
- The identified conserved regulatory elements and SNPs in MAPT provide a basis for understanding its role in neurodegeneration.
- Further research into these genetic factors may elucidate disease mechanisms and identify therapeutic targets.