title: An extended 5'-tau susceptibility haplotype in progressive supranuclear palsy.
abstract: OBJECTIVE
  To confirm the association of an extended 5'-tau haplotype on chromosome 17q with the disease phenotype in clinically ascertained individuals with sporadic progressive supranuclear palsy (PSP).
  
  
  BACKGROUND
  PSP is a neurodegenerative disease with parkinsonian signs accompanied by vertical supranuclear palsy and tau pathologic features. Previously, we documented the complete segregation of an extended 5'-tau haplotype consisting of four single nucleotide polymorphisms (SNP) with the disease phenotype in sporadic PSP. This study was conducted in an independent cohort to confirm these results and to improve the statistical power of the data.
  
  
  METHODS
  Direct sequencing and restriction enzyme digests were used to analyze four SNP in tau Exons 1, 4A, and 8. These contiguous SNP were used to reconstruct an extended 5'-tau haplotype in 52 affected and 54 age-matched control individuals.
  
  
  RESULTS
  The four SNP formed two homozygous 5'-tau haplotypes (HapA and HapC) or a heterozygous genotype. Fifty-one (98%) patients with PSP had HapA; one (2%) with a later onset was heterozygous; and none had HapC. These PSP haplotype frequencies were different (p < 0.00001) from those of the age-matched control group, in which 18 (33%) people had HapA; 26 (48%) were heterozygous; and 10 (19%) had HapC. The extended 5'-tau haplotype, HapA, had a high sensitivity (98%) and a moderate specificity (67%) as a marker for PSP.
  
  
  CONCLUSIONS
  A 5'-tau susceptibility haplotype may be a sensitive marker for sporadic PSP and a genetic defect in, or closely linked to, tau may contribute to the cause of PSP.
authors.affiliation: Laboratory of Clinical Neurogenetics, Wadsworth Center, New York State Department of Health, Albany, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Higgins
authors.forename: L I
authors.initials: LI
authors.lastname: Golbe
authors.forename: A
authors.initials: A
authors.lastname: De Biase
authors.forename: J
authors.initials: J
authors.lastname: Jankovic
authors.forename: S A
authors.initials: SA
authors.lastname: Factor
authors.forename: R L
authors.initials: RL
authors.lastname: Adler
mesh_terms: D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; D016875:tau Proteins