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Published on: January 9, 2020
Functional MAPT haplotypes: bridging the gap between genotype and neuropathology
Tara M Caffrey1, Richard Wade-Martins
1The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Neurobiology of Disease
|June 9, 2007
Summary
The microtubule-associated protein tau (MAPT) locus is linked to neurodegenerative diseases. New research reveals functional mechanisms connecting MAPT haplotypes to disease pathology.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- The microtubule-associated protein tau (MAPT) locus is genetically associated with neurodegenerative disorders like Alzheimer's, Parkinson's, progressive supranuclear palsy, and corticobasal degeneration.
- The genomic region of MAPT is complex, characterized by a large linkage disequilibrium block and two main haplotypes (H1 and H2) shaped by numerous SNPs and a recombination-suppressing inversion.
Purpose of the Study:
- To review the role of MAPT in sporadic and familial neurodegenerative diseases.
- To discuss emerging functional mechanisms linking MAPT haplotypes to neuropathology.
Main Methods:
- Review of existing literature on MAPT genetics and neurodegenerative diseases.
- Analysis of fine-mapping studies identifying disease-associated MAPT sub-haplotypes.
- Discussion of proposed functional mechanisms connecting haplotypes to pathology.
Main Results:
- Specific sub-clades of the MAPT H1 haplotype have been identified as being associated with increased risk for neurodegenerative diseases.
- Emerging research is beginning to elucidate the functional biological pathways that explain the genetic association between MAPT and disease.
Conclusions:
- The MAPT locus plays a significant role in the pathogenesis of various neurodegenerative diseases.
- Understanding the functional mechanisms underlying MAPT haplotype associations is crucial for deciphering disease etiology and developing targeted therapies.
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