Human Molecular Genetics Advance Access published online on August 4, 2008
Human Molecular Genetics, doi:10.1093/hmg/ddn222
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Dynamic variation in allele-specific gene expression of Paraoxonase-1 in murine and human tissues
1 Department of Genetics and Genomic Biology, Hospital for Sick Children, Toronto M5G 1X8, Canada 2 Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada 3 Institute of Child Health, 30 Guilford Street, London, WC1 N 1EH, UK
* To whom correspondence should be addressed Corresponding author: Stephen W. Scherer The Hospital for Sick Children MaRS Centre - East Tower 101 College Street, Room 14-706 Toronto, Ontario, M5G 1L7, Canada Telephone: (416) 813-7613 Fax: (416) 813-8319 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 fetal 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.
4 Current Address: Department of Maternal-Fetal Biology, National Center for Child Health and Development, Tokyo, Japan