Molecular evolution and genetics of the Saitohin gene in Alzheimer's disease and argyrophilic grain disease

A novel gene, Saitohin (STH), has been discovered in the intron between exons 9 and 10 of the human tau gene. The tissue expression of STH is similar to tau, a gene that is implicated in many neurodegenerative disorders. In humans, a single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in STH and was found to be over-represented in the homozygous state in late onset Alzheimer’s disease (AD) subjects. A subsequent genetic study of the STH/Tau gene locus was performed with AD subjects and argyrophilic grain disorder (AGD) subjects to determine whether there is a correlation between the Q7R polymorphism and their respective Braak pathological stages. Since nucleotide and amino acid sequence analyses of the STH gene show it has no clear homology to known genes, proteins, signal sequences or motifs, the molecular evolution of the STH gene was undertaken to identify consensus of the protein and identify its putative domains as a result of the conservation of amino acids. Taken together, these results will provide further insight into not only the possible pathological role in AD and AGD but the biology of STH itself.