title: Identification of a novel valosin-containing protein polymorphism in late-onset Alzheimer's disease.
abstract: OBJECTIVE
  Recently, mutations in the valosin-containing protein gene (VCP) were found to be causative for a rare form of dementia [Watts GDJ, et al.: Nat Genet 2004;36:377-381]. This gene lies within a region on the genome that has been linked to late onset Alzheimer's disease (LOAD) [Myers A, et al.: Am J Med Genet 2002;114:233-242]. In this study, we investigated whether variation within VCP could account for the LOAD linkage peak on chromosome 9.
  
  
  METHODS
  We sequenced 188 individuals from the set of sibling pairs we had used to obtain the linkage results for chromosome 9 to look for novel polymorphisms that could explain the linkage signal. Any variant that was found was then typed in 2 additional sets of neuropathologically confirmed samples to look for associations with Alzheimer's disease.
  
  
  RESULTS
  We found 2 variants when we sequenced VCP. One was a novel rare variant (R92H) and the other is already reported within the publicly available databases (rs10972300). Neither explained the chromosome 9 linkage signal for LOAD.
  
  
  CONCLUSIONS
  We have found a novel rare variant within the VCP gene, but we did not find a variant that could explain the linkage signal for LOAD on chromosome 9.
authors.affiliation: Laboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kaleem
authors.forename: A
authors.initials: A
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Hamshere
authors.forename: A J
authors.initials: AJ
authors.lastname: Myers
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D005819:Genetic Markers; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein