Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders

Amy Webb, Bruce Miller, Stephen J Bonasera, Adam Boxer, Anna Karydas, Kirk C. Wilhelmsen

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: An inverted region on chromosome 17 has been previously linked to many Pick complex diseases. Due to the inversion, an exact causal locus has been difficult to identify, but the microtubule-associated protein tau gene is a likely candidate gene for its involvement in these diseases with tau inclusion. Objective: To search for variants that confer susceptibility to 4 tauopathies and clinically related disorders. Design: Genomewide association study. Setting: University research laboratory. Participants: A total of 231 samples were genotyped from an unrelated white population of patients with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia, and frontotemporal dementia with amyotrophy. Unaffected individuals from the same population were used as controls. Main Outcome Measures: The results from an inverted region of chromosome 17 that contains the MAPT gene. Genotypes of cases and controls were compared using a Fisher exact test on a marker-by-marker basis. Haplotypes were determined by visually inspecting genotypes. Results: Comparing any particular disease and controls, the association was constant across the inverted chromosome segment. Significant associations were seen for PSP and PSP combined with CBD. Of the 2 haplotypes seen in the region, H1 was overrepresented in PSP and CBD cases compared with controls. Conclusions: As expected, the markers are highly correlated and the association is seen across the entire region, which makes it difficult to narrow down a disease-causing variant or even a possible candidate gene. However, considering the pathologic abnormalities of these diseases and the involvement of tau mutations seen in familial forms, the MAPT gene represents the most likely cause driving the association.

Original languageEnglish (US)
Pages (from-to)1473-1478
Number of pages6
JournalArchives of Neurology
Volume65
Issue number11
DOIs
StatePublished - Nov 1 2008

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Progressive Supranuclear Palsy
Frontotemporal Dementia
Chromosomes, Human, Pair 17
Genes
Haplotypes
Genotype
Pick Disease of the Brain
Tauopathies
Microtubule-Associated Proteins
Population
Chromosomes
Outcome Assessment (Health Care)
Inversion
Chromosome
Degeneration
Gene
Mutation
Research

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders. / Webb, Amy; Miller, Bruce; Bonasera, Stephen J; Boxer, Adam; Karydas, Anna; Wilhelmsen, Kirk C.

In: Archives of Neurology, Vol. 65, No. 11, 01.11.2008, p. 1473-1478.

Research output: Contribution to journalArticle

Webb, Amy ; Miller, Bruce ; Bonasera, Stephen J ; Boxer, Adam ; Karydas, Anna ; Wilhelmsen, Kirk C. / Role of the tau gene region chromosome inversion in progressive supranuclear palsy, corticobasal degeneration, and related disorders. In: Archives of Neurology. 2008 ; Vol. 65, No. 11. pp. 1473-1478.
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