Located on chromosome 17, the microtubule-associated protein tau gene, MAPT, encodes the tau proteins found in humans primarily in neurons and best known medically for their role in CNS disorders such as Alzheimer's disease and frontotemporal dementia. There are six main forms ("isoforms") of tau proteins, produced by alternative splicing of the MAPT gene.Wikipedia
An inversion polymorphism arising about 3 million years ago of approximately 900kb on chromosome 17q21 and including the MAPT gene defines two haplotype clades, H1 and H2.[PMID 15654335] Since that time, the H1 and H2 haplotypes have been recombinationally suppressed and have accumulated sequence variations. As a result, any one of a large number of SNPs within the 900kb can be genotyped to distinguish the two haplotypes. In general, H2 haplotypes are rare in Africans, almost absent in East Asians but found at a frequency of 20% in Europeans.
Studies have linked the MAPT H1/H1 diplotype to increased risk for certain neuropathologies. For example, a 2007 study of 1,000+ patients with Parkinson's disease found a significant association between the H1/H1 genotype and risk of disease (OR 1.46, CI: 1.25-1.69, p = 8 x 10e-7).[PMID 17514749]
It is now known that further variations within each haplotype (clade) define subhaplotypes (subclades), and for some disorders, risk differs between subclades. For example, the H1c subhaplotype of MAPT was associated with increased risk for Alzheimer's disease in 360 autopsy-confirmed cases.[PMID 16000317]
Mutations within the MAPT gene have also been linked to frontotemporal dementia and Pick's disease.