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. DESIGN AND 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.
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. DESIGN AND 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: Stacey Melquist; David W Craig; Matthew J Huentelman; Richard Crook; John V Pearson; Matt Baker; Victoria L Zismann; Jennifer Gass; Jennifer Adamson; Szabolcs Szelinger; Jason Corneveaux; Ashley Cannon; Keith D Coon; Sarah Lincoln; Charles Adler; Paul Tuite; Donald B Calne; Eileen H Bigio; Ryan J Uitti; Zbigniew K Wszolek; Lawrence I Golbe; Richard J Caselli; Neill Graff-Radford; Irene Litvan; Matthew J Farrer; Dennis W Dickson; Mike Hutton; Dietrich A Stephan Journal: Am J Hum Genet Date: 2007-03-08 Impact factor: 11.025
Authors: Sofia A Oliveira; William K Scott; Fengyu Zhang; Jeffrey M Stajich; Kenichiro Fujiwara; Michael Hauser; Burton L Scott; Margaret A Pericak-Vance; Jeffery M Vance; Eden R Martin Journal: Neurogenetics Date: 2004-06-08 Impact factor: 2.660
Authors: Naomi Kouri; Owen A Ross; Beth Dombroski; Curtis S Younkin; Daniel J Serie; Alexandra Soto-Ortolaza; Matthew Baker; Ni Cole A Finch; Hyejin Yoon; Jungsu Kim; Shinsuke Fujioka; Catriona A McLean; Bernardino Ghetti; Salvatore Spina; Laura B Cantwell; Martin R Farlow; Jordan Grafman; Edward D Huey; Mi Ryung Han; Sherry Beecher; Evan T Geller; Hans A Kretzschmar; Sigrun Roeber; Marla Gearing; Jorge L Juncos; Jean Paul G Vonsattel; Vivianna M Van Deerlin; Murray Grossman; Howard I Hurtig; Rachel G Gross; Steven E Arnold; John Q Trojanowski; Virginia M Lee; Gregor K Wenning; Charles L White; Günter U Höglinger; Ulrich Müller; Bernie Devlin; Lawrence I Golbe; Julia Crook; Joseph E Parisi; Bradley F Boeve; Keith A Josephs; Zbigniew K Wszolek; Ryan J Uitti; Neill R Graff-Radford; Irene Litvan; Steven G Younkin; Li-San Wang; Nilüfer Ertekin-Taner; Rosa Rademakers; Hakon Hakonarsen; Gerard D Schellenberg; Dennis W Dickson Journal: Nat Commun Date: 2015-06-16 Impact factor: 14.919
Authors: Pascual Sánchez-Juan; Matthew T Bishop; Alison Green; Claudia Giannattasio; Alejandro Arias-Vasquez; Anna Poleggi; Richard S G Knight; Cornelia M van Duijn Journal: BMC Med Genet Date: 2007-12-11 Impact factor: 2.103