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Human Molecular Genetics Advance Access originally published online on August 4, 2008
Human Molecular Genetics 2008 17(21):3263-3270; doi:10.1093/hmg/ddn222
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Dynamic variation in allele-specific gene expression of Paraoxonase-1 in murine and human tissues

Layla Parker-Katiraee1,2, Eleni Bousiaki3, David Monk3, Gudrun E. Moore3, Kazuhiko Nakabayashi1,{dagger} and Stephen W. Scherer1,2,*

1 Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada M5G 1X8 2 Department of Molecular Genetics, University of Toronto, Toronto, Canada M5S 1A8 3 Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK

* To whom correspondence should be addressed at: The Hospital for Sick Children, MaRS Centre—East Tower, Room 14-706, 101 College Street, Toronto, Ontario, Canada M5G 1L7. Tel: +1 4168137613; Fax: +1 4168138319; Email: steve{at}genet.sickkids.on.ca

Received April 29, 2008; Revised July 11, 2008; Accepted July 30, 2008

Differential allelic expression has been shown to be common in mice, humans and maize, and variability in the expression of polymorphic alleles has been associated with human disease. Here, we describe the differential expression pattern of Paraoxonase-1, a gene involved in lipid metabolism and implicated in the formation of atherosclerotic lesions. We measured the expression of the murine Paraoxonase-1 gene (Pon1) in livers at different stages of embryonic development using F1 hybrid crosses and quantified the transcriptional level of both parental alleles. Using human foetal tissues, we analysed the expression of the human orthologue (PON1) and found monoallelic or preferential allelic expression in 6/7 and 4/4 samples from liver and pancreas, respectively. We observed that Pon1 does not show a parent-of-origin preference in its allelic expression, but has dramatic variations in allele-specific expression occurring throughout development. This study has important repercussions in the analysis of haplotypes at disease loci, since it implies that the expression of polymorphic alleles can be unequal and dynamic.

{dagger} Present address: Department of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan.


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