TY - JOUR
T1 - Molecular evolution and genetics of the Saitohin gene and tau haplotype in Alzheimer's disease and argyrophilic grain disease
AU - Conrad, Chris
AU - Vianna, Cintia
AU - Schultz, Christian
AU - Thal, Dietmar R.
AU - Ghebremedhin, Estifanos
AU - Lenz, Jack
AU - Braak, Heiko
AU - Davies, Peter
PY - 2004/4
Y1 - 2004/4
N2 - A single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in the Saitohin (STH) gene and was initially found to be over-represented in the homozygous state in subjects with late-onset Alzheimer's disease (AD). More extensive studies provide limited support for the association with AD, but confirm an association of the Q allele with progressive supranuclear palsy and argyrophilic grain disease. A homologous sequence was found in the appropriate location of the rat and mouse tau genes, but there was no open reading frame allowing STH expression in these species, suggesting relatively recent evolution of this gene. In some non-human primates, the STH gene was identified, and this was found to differ from the human gene at two of 128 amino acids. All primates in which the STH gene was identified were homozygous for the R allele of STH, suggesting this is the ancestral allele. This observation was surprising, in that the Q allele is more common in human populations, and raises the possibility that natural selection has operated to favor individuals carrying this allele. The STH polymorphism is part of the tau gene haplotype, of which two major variants exist in human populations, the Q being part of the H1 haplotype and the R part of the H2 haplotype. More detailed studies confirm the H2 haplotype to be the ancestral tau gene. This situation is reminiscent of the evolution of the apolipoprotein (ApoE) gene, another locus that is potentially important for the risk of development of AD.
AB - A single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in the Saitohin (STH) gene and was initially found to be over-represented in the homozygous state in subjects with late-onset Alzheimer's disease (AD). More extensive studies provide limited support for the association with AD, but confirm an association of the Q allele with progressive supranuclear palsy and argyrophilic grain disease. A homologous sequence was found in the appropriate location of the rat and mouse tau genes, but there was no open reading frame allowing STH expression in these species, suggesting relatively recent evolution of this gene. In some non-human primates, the STH gene was identified, and this was found to differ from the human gene at two of 128 amino acids. All primates in which the STH gene was identified were homozygous for the R allele of STH, suggesting this is the ancestral allele. This observation was surprising, in that the Q allele is more common in human populations, and raises the possibility that natural selection has operated to favor individuals carrying this allele. The STH polymorphism is part of the tau gene haplotype, of which two major variants exist in human populations, the Q being part of the H1 haplotype and the R part of the H2 haplotype. More detailed studies confirm the H2 haplotype to be the ancestral tau gene. This situation is reminiscent of the evolution of the apolipoprotein (ApoE) gene, another locus that is potentially important for the risk of development of AD.
KW - Apolipoprotein E
KW - Evolution
KW - Saitohin
KW - Tau
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U2 - 10.1046/j.1471-4159.2004.02320.x
DO - 10.1046/j.1471-4159.2004.02320.x
M3 - Article
C2 - 15030402
AN - SCOPUS:1842457770
SN - 0022-3042
VL - 89
SP - 179
EP - 188
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -