The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts.
Previously we have shown that the H1c haplotype on the background of the H1 clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD). Here we replicated the association with AD in an additional autopsy confirmed series. We show that this haplotype increases both the expression of total MAPT transcript as well as specifically increasing the proportion of 4 microtubule binding repeat containing transcripts. We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.
Myers
Amanda J
AJ
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA.
Pittman
Alan M
AM
Zhao
Alice S
AS
Rohrer
Kristen
K
Kaleem
Mona
M
Marlowe
Lauren
L
Lees
Andrew
A
Leung
Doris
D
McKeith
Ian G
IG
Perry
Robert H
RH
Morris
Chris M
CM
Trojanowski
John Q
JQ
Clark
Christopher
C
Karlawish
Jason
J
Arnold
Steve
S
Forman
Mark S
MS
Van Deerlin
Vivianna
V
de Silva
Rohan
R
Hardy
John
J
D017668:Age of Onset; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009447:Neuroblastoma; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D024801:Tauopathies / Q000453:epidemiology / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D012333:RNA, Messenger; D016875:tau Proteins