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Transcriptional regulation in the MAPT H1/H2 Haplotype Block
Author(s) -
Rhodes C. Harker,
Haroutunian V,
Katsel P,
Tsongalis G J,
Lefferts J A,
Sibille E,
Lathrop M J,
Fiering S N
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.173.10
Subject(s) - haplotype , genetics , locus (genetics) , biology , gene , allele
The protective effect of the MAPT H2 haplotype against neurodegenerative diseases suggested that a genome wide screen comparing normal control individuals with and without an H2‐containing chromosome might provide insights into the molecular biology of those diseases. RNA from the anterior cingulate and amygdala from 18 individuals with no neurologic disease was examined by U133 expression array analysis. Four of the subjects were heterozygous for the MAPT H1/H2 haplotype, one subject was an H2 homozygote, and the remaining 13 were H1 homozygotes. Comparison of H1 homozygotes and H2 carriers revealed 5 transcripts which were expressed at significantly higher levels in H2‐carriers. This result was confirmed by a quantitative PCR assay of one of the transcripts and by U133 array analysis of RNA from multiple brain areas in an independent cohort. All five transcripts map to the 1 Mb inversion containing the MAPT locus. None of the transcripts comes from a named gene or contains a known miRNA. The coordinated up‐regulation of these transcripts suggests a global difference in transcriptional regulation in the H1 and H2 chromosomes. This hypothesis is in contrast to, but is not mutually exclusive with, the usual explanation that the protective effect of the H2 haplotype is due to specific functional polymorphisms.