Linkage disequilibrium and association of MAPT H1 in Parkinson disease.
The MAPT H1 haplotype has been associated with four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. More controversial is that the same haplotype has been associated with Parkinson disease (PD). Using H1-specific single-nucleotide polymorphisms, we demonstrate that MAPT H1 is a misnomer and consists of a family of recombining H1 alleles. Population genetics, linkage disequilibrium, and association analyses have shown that specific MAPT H1 subhaplotypes are preferentially associated with Parkinson disease. Using a sliding scale of MAPT H1-specific haplotypes--in age/sex-matched PD cases and controls from central Norway--we have refined the disease association to within an approximately 90-kb interval of the 5' end of the MAPT locus.
Skipper
Lisa
L
Laboratories of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Wilkes
Kristen
K
Toft
Mathias
M
Baker
Matthew
M
Lincoln
Sarah
S
Hulihan
Mary
M
Ross
Owen A
OA
Hutton
Mike
M
Aasly
Jan
J
Farrer
Matthew
M
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002874:Chromosome Mapping; D015331:Cohort Studies; D017931:DNA Primers; D005260:Female; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009664:Norway; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D016875:tau Proteins
D017931:DNA Primers; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D016875:tau Proteins