title: Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner.
abstract: BACKGROUND
  Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry. Two divergent MAPT haplotypes, H1 and H2 are described with distinct linkage disequilibrium patterns across the region reflecting the inversion status at this locus. The MAPT H1 haplotype has been associated with progressive supranuclear palsy, corticobasal degeneration, Parkinson's disease and Alzheimer's disease, while the H2 is linked to recurrent deletion events associated with the 17q21.31 microdeletion syndrome, a disease characterized by developmental delay and learning disability.
  
  
  RESULTS
  In this study, we investigate the effect of the inversion on the expression of genes in the 17q21.31 region. We find the expression of several genes in and at the borders of the inversion to be affected; specific either to whole blood or different regions of the human brain. The H1 haplotype was found to be associated with an increased expression of LRRC37A4, PLEKH1M and MAPT. In contrast, a decreased expression of MGC57346, LRRC37A and CRHR1 was associated with H1.
  
  
  CONCLUSIONS
  Studies thus far have focused on the expression of MAPT in the inversion region. However, our results show that the inversion status affects expression of other genes in the 17q21.31 region as well. Given the link between the inversion status and different neurological diseases, these genes may also be involved in disease pathology, possibly in a tissue-specific manner.
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht3584 CG, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: de Jong
authors.forename: Iouri
authors.initials: I
authors.lastname: Chepelev
authors.forename: Esther
authors.initials: E
authors.lastname: Janson
authors.forename: Eric
authors.initials: E
authors.lastname: Strengman
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D001483:Base Sequence; D001769:Blood / Q000378:metabolism; D001921:Brain / Q000473:pathology; D007446:Chromosome Inversion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005060:Europe; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics; D011110:Polymorphism, Genetic; D025341:Principal Component Analysis; D017422:Sequence Analysis, DNA; D013494:Supranuclear Palsy, Progressive / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins