title: Novel interleukin-1 receptor antagonist exon polymorphisms and their use in allele-specific mRNA assessment.
abstract: A variable number of tandem repeats (VNTR) polymorphism has been described in intron 2 of the interleukin-1 receptor antagonist gene. Allele 2 of this polymorphism is associated with many chronic inflammatory diseases. Using direct sequencing of polymerase chain reaction products from individuals of known genotype for the VNTR, we have identified four single base change polymorphisms in exons 1ic and 2 and one upstream of exon 1ic, all of which are probably in linkage disequilibrium with the intron 2 VNTR. The exonic polymorphisms do not alter the encoded amino acid sequence. Using the exon 2 polymorphism as a marker for the intron 2 disease-associated allele, we have been able to analyse allele-specific mRNA in heterozygotic keratinocyte cell lines. The disease-associated allele shows no difference from other alleles in this cell type with respect to mRNA accumulation.
authors.affiliation: Section of Molecular Medicine, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: F E
authors.initials: FE
authors.lastname: Clay
authors.forename: J K
authors.initials: JK
authors.lastname: Tarlow
authors.forename: M J
authors.initials: MJ
authors.lastname: Cork
authors.forename: A
authors.initials: A
authors.lastname: Cox
authors.forename: M J
authors.initials: MJ
authors.lastname: Nicklin
authors.forename: G W
authors.initials: GW
authors.lastname: Duff
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007438:Introns / Q000235:genetics; D015603:Keratinocytes; D018459:Lichen Sclerosus et Atrophicus / Q000235:genetics*; D015810:Linkage Disequilibrium; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D012795:Sialoglycoproteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D012795:Sialoglycoproteins