title: Polymorphisms of human TAP2 detected by denaturing gradient gel electrophoresis.
abstract: The human transporter associated with antigen processing (TAP1 and TAP2) genes are located in the human leukocyte antigen (HLA) class II region of the genome and encode proteins that form a heterodimer essential for the transport of endogenous peptides into the endoplasmic reticulum for assembly with HLA class I molecules. Type 1 diabetes is an autoimmune disease that is associated with the HLA region of the genome, with HLA class II genes conferring the greatest statistical risk. The presentation of self-peptides by HLA class I molecules is defective in individuals with this disease, and both TAP1 and TAP2 are potential contributors to this defect. Denaturing gradient gel electrophoresis (DGGE) was applied to screen all 11 exons and the 3' flanking region of TAP2 for polymorphisms in individuals with type 1 diabetes patients and controls. Seventy polymorphisms, including 51 in introns, 4 in the 3' flanking region, and 15 in exons, were identified. Sequencing of polymorphic DNA fragments revealed several new polymorphisms, including a Gln --> Arg substitution at codon 611 and a GT --> GC polymorphism affecting the donor splice site of intron 4, that might be of functional significance. None of the polymorphisms examined differed in frequency between individuals with type 1 diabetes and controls.
authors.affiliation: Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Penfornis
authors.forename: Gang
authors.initials: G
authors.lastname: Yan
authors.forename: Lijia
authors.initials: L
authors.lastname: Shi
authors.forename: Denise L
authors.initials: DL
authors.lastname: Faustman
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D018929:Cell Culture Techniques; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods*; D005091:Exons; D005802:Genes, MHC Class II; D015894:Genome, Human; D006801:Humans; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; C071692:TAP2 protein, human