Identification of a novel valosin-containing protein polymorphism in late-onset Alzheimer's disease.
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.
Kaleem
M
M
Laboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20892, USA.
Zhao
A
A
Hamshere
M
M
Myers
A J
AJ
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
D018797:Cell Cycle Proteins; D005819:Genetic Markers; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein