A polymorphic gene nested within an intron of the tau gene: Implications for Alzheimer's disease

Abstract

A previously undescribed gene, Saitohin (STH), has been discovered in the intron between exons 9 and 10 of the human tau gene. STH is an intronless gene that encodes a 128-aa protein with no clear homologs. 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 used in a case control study. The Q7R polymorphism appears to be over-represented in the homozygous state in late onset Alzheimer's disease subjects.

Haplotypes and gene expression implicate the MAPT region for Parkinson disease

“…15 There is immunohistochemical evidence that STH produces a protein product, 15 but studies have demonstrated that STH may be involved in the regulation of 3R and 4R MAPT splicing. 36,37 In the current study, it was found that higher expression of STH was strongly correlated with higher expression of both 3R and 4R MAPT isoforms across all samples.…”

“…STH, a single-exon gene located within intron 9 of MAPT, has shown similar tissue distribution to MAPT, suggesting that the two genes may be co-regulated in certain tissue types. 15 The finding of modest evidence for linkage to PD affection in the GenePD Study (nonparametric lod score = 1.7 on chromosome 17 at 63.8-63.9 cM) justified an examination of the MAPT region. We analyzed the association of 21 SNPs spanning MAPT, STH, and KIAA1267 to PD in the GenePD Study.…”

Infectious delivery of the 132 kb CDKN2A/CDKN2B genomic DNA region results in correctly spliced gene expression and growth suppression in glioma cells

“…The complexity of gene expression includes alternative splicing mechanisms, 1 alternative promoter-enhancer usage, 2 intronic gene expression, 3 expression of inhibiting RNAs, 4 and effects of DNA polymorphisms. 5 Such mechanisms likely account for the large diversity of proteins (greater than 100 000 per cell) derived from a relatively small number of human genes (around 30 000) and for their expression with tissue and developmental specificity.…”

From Protein Tangles to Genetic Variants: The Central Role of Tau in Neurodegenerative Disease

“…Subsequently, the H1 haplotype was further expanded to include the promoter region of MAPT and now spans a region of ~1.8Mb in complete linkage disequilibrium (de Silva et al, 2001;Pittman et al, 2004). This extended haplotype contains several genes in addition to MAPT, including CRHR1 (corticotrophin-releasing hormone receptor 1), NSF (Nethylmaleimide sensitive factor), IMP5 (intramembrane protease 5), WNT3 and STH (saitohin), a gene nested in the intron 9 of MAPT (Conrad et al, 2002;Pittman et al, 2004). A ~900kb segment of the H2 haplotype including MAPT has been found to be inverted in respect to H1.…”