title: Identification of novel Tapasin polymorphisms and linkage disequilibrium to MHC class I alleles.
abstract: Tapasin is a Mr 48,000 glycoprotein and has a specialized role in MHC class I-restricted antigen presentation. It is encoded by a gene which maps centromeric to the MHC class II region of human Chromosome 6 within 200 kb of HLA-DP. There is variable dependence upon tapasin for MHC class I expression among different MHC class I alleles. HLA-B*4402 and to a lesser extent HLA-A1 and B8 are tapasin dependent, whereas HLA-B27, A2 and to a lesser extent B7 and A3 are tapasin independent. We investigated whether tapasin is polymorphic and whether these Tapasin alleles are in linkage with any MHC class I alleles. We identified three new mutations within intron 4, which are in a particular linkage with the previously described exon 4 (G16003C) dimorphism. The intronic mutations are G16146T, G16232A, and T16317A (numbering according to cosmid clone F0811; GenBank accession number Z97184). The allele frequency of Tapasin*01 (G16003) was 0.47 and Tapasin*02 (C16003) was 0.53 in this UK population. Four of the eight possible intronic haplotypes were identified and their cis linkage with the tapasin dimorphism ascertained. Tapasin*01 was associated with all the identified haplotypes, while Tapasin*02 was only associated with the wild-type intronic sequence (GGT). There was no significant linkage (P>0.01) of the Tapasin dimorphism or new Tapasin alleles to any of the MHC class I A, B, or C alleles studied or to the extended A1 B8 DR3 haplotype.
authors.affiliation: Nuffield Department of Medicine, Institute of Molecular Medicine, Oxford, UK. anthony.williams@ndm.ox.ac.uk
authors.forename: A P
authors.initials: AP
authors.lastname: Williams
authors.forename: S
authors.initials: S
authors.lastname: Bevan
authors.forename: M
authors.initials: M
authors.lastname: Bunce
authors.forename: R
authors.initials: R
authors.lastname: Houlston
authors.forename: K I
authors.initials: KI
authors.lastname: Welsh
authors.forename: T
authors.initials: T
authors.lastname: Elliott
mesh_terms: D000328:Adult; D000483:Alleles; D017920:Antiporters / Q000235:genetics*; D001483:Base Sequence; D018076:DNA, Complementary; D005787:Gene Frequency; D006023:Glycoproteins / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D015810:Linkage Disequilibrium; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
chemical_list: D017920:Antiporters; D018076:DNA, Complementary; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C107762:tapasin