title: Genetic polymorphism of the human ICOS gene.
abstract: Inducible costimulator (ICOS) is a novel receptor belonging to the same family as CD28 and CTLA4, which regulate T-lymphocyte activation in the immune response. The genes for these molecules are located adjacent to each other on Chromosome 2q33. Many autoimmune diseases have been found to be genetically linked to or associated with genetic markers near the CTLA4 gene. However, as all three genes are closely linked and have related functions, it is possible that the findings could be explained by variation in CD28 or ICOS. Few data on genetic variation in the ICOS gene are available. We sequenced the ICOS gene in 13 healthy unrelated individuals and found eight single nucleotide polymorphisms. One was located in the first intron, and the others in the untranslated region of the last exon. The allele frequencies and linkage disequilibrium were determined from a population sample of 63 Finnish individuals. The results show that the ICOS gene is polymorphic, but no variation in the coding sequence was detected, implying that the genetic linkage of this gene region to autoimmune diseases may not result from structural variation in the ICOS molecule. These polymorphisms, however, should be useful in genetic studies of this candidate gene.
authors.affiliation: Finnish Red Cross Blood Transfusion Service, Department of Tissue Typing, Kivihaantie 7, 00310 Helsinki, Finland.
authors.forename: Katri E
authors.initials: KE
authors.lastname: Haimila
authors.forename: Jukka A
authors.initials: JA
authors.lastname: Partanen
authors.forename: Päivi M
authors.initials: PM
authors.lastname: Holopainen
mesh_terms: D000069594:Abatacept; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D018106:CD28 Antigens / Q000235:genetics; D060908:CTLA-4 Antigen; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005387:Finland; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D018796:Immunoconjugates; D060889:Inducible T-Cell Co-Stimulator Protein; D007438:Introns; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018076:DNA, Complementary; C556692:ICOS protein, human; D018796:Immunoconjugates; D060889:Inducible T-Cell Co-Stimulator Protein; D000069594:Abatacept