Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.
Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes.
van Endert
P M
PM
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5402.
Lopez
M T
MT
Patel
S D
SD
Monaco
J J
JJ
McDevitt
H O
HO
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000941:Antigens / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003062:Codon; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D010443:Peptide Chain Termination, Translational; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D046988:Proteasome Endopeptidase Complex; D011995:Recombination, Genetic
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D002352:Carrier Proteins; D003062:Codon; D000949:Histocompatibility Antigens Class II; D009097:Multienzyme Complexes; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex