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

Published

Journal Article

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

Full Text

Duke Authors

Cited Authors

  • Oliveira, SA; Scott, WK; Zhang, F; Stajich, JM; Fujiwara, K; Hauser, M; Scott, BL; Pericak-Vance, MA; Vance, JM; Martin, ER

Published Date

  • September 2004

Published In

Volume / Issue

  • 5 / 3

Start / End Page

  • 147 - 155

PubMed ID

  • 15459824

Pubmed Central ID

  • 15459824

Electronic International Standard Serial Number (EISSN)

  • 1364-6753

International Standard Serial Number (ISSN)

  • 1364-6745

Digital Object Identifier (DOI)

  • 10.1007/s10048-004-0180-5

Language

  • eng