Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner

Simone De Jong,Iouri Chepelev,Leonard H Van Den Berg,Roel A Ophoff,Eric Strengman,Jan H Veldink,Esther Janson

doi:10.1186/1471-2164-13-458

Abstract

BackgroundChromosome 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.ResultsIn 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.ConclusionsStudies 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.

Highlights

Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry
Specific H1 haplotypes are associated with the neurodegenerative disorders, whereas the H2 haplotype is linked to recurrent deletion events resulting in the 17q21.31 microdeletion syndrome, characterized by developmental delay and learning disability [7,8]
Specific H1 haplotypes are associated with neurodegenerative disorders such as progressive supranuclear palsy [1] and Parkinson’s disease [3], whereas the H2 haplotype is associated with recurrent microdeletions resulting in the 17q21.31 microdeletion syndrome [7,8]

Summary

Introduction

Chromosome 17q21.31 contains a common inversion polymorphism of approximately 900 kb in populations with European ancestry. 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. The chromosomal band 17q21.31 contains a common inversion polymorphism linked with neurodegenerative diseases including progressive supranuclear palsy [1], corticobasal degeneration [2], Parkinson’s disease [3], and Alzheimer’s disease [4]. This inversion of approximately 900 kb is mostly present in populations with European ancestry (Figure 1) [5,6]. Little is de Jong et al BMC Genomics 2012, 13:458 http://www.biomedcentral.com/1471-2164/13/458

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