title: Dynamic variation in allele-specific gene expression of Paraoxonase-1 in murine and human tissues.
abstract: 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.
authors.affiliation: Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada.
authors.forename: Layla
authors.initials: L
authors.lastname: Parker-Katiraee
authors.forename: Eleni
authors.initials: E
authors.lastname: Bousiaki
authors.forename: David
authors.initials: D
authors.lastname: Monk
authors.forename: Gudrun E
authors.initials: GE
authors.lastname: Moore
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D000483:Alleles; D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics*; D019175:DNA Methylation; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D010179:Pancreas / Q000196:embryology / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D043303:Aryldialkylphosphatase; C468406:PON1 protein, human