Linkage disequilibrium and haplotype tagging polymorphisms in the Tau H1 haplotype.

摘要: We and others have previously detected association of the Tau H1 haplotype on chromosome 17 with risk idiopathic Parkinson disease (PD). The appears to a fundamental importance in neurodegeneration, as multiple studies shown it is also associated an increased for progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration syndromes, primary aphasia. Therefore, divide into sub-haplotypes that could be more significantly developing PD, delimit genes lying haplotype, we analyzed 34 single nucleotide polymorphisms (SNPs) spanning over 3.15 megabases region containing Tau. These SNPs are located or flank corticotropin-releasing hormone receptor 1, presenilin homolog 2, Tau, Saitohin, KIAA1267 genes. Analysis linkage disequilibrium (LD) using these suggests extends about 1.3 megabases, making largest LD reported date. Of 29 this LD, 5 were identified “haplotype tagging” (htSNPs), capturing 96% sample’s diversity. Association analysis htSNPs revealed new sub-haplotype PD (P<0.02). results define regulatory regions included important susceptibility allele contributing neurodegeneration.