title: DQA1*03 subtypes have different associations with DRB1 and DQB1 alleles.
abstract: Polymorphisms outside the hypervariable regions of HLA class II alleles that do not affect the peptide-binding site are probably not under selective pressure and could therefore be useful as markers of the evolutionary pathways of the HLA class II haplotypes. We have analyzed such a polymorphism in the variants of DQA1*03, which differ at residue 160 encoded in exon 3. Our study included homozygous BCLs of the 10th IHWS and samples of a multiracial panel of 723 unrelated subjects which were also typed for allelic variations in exon 2 by hybridization with SSOP. BCLs having DQA1*03 and 131 selected DQA1*03-positive samples were typed for the dimorphism in exon 3 that distinguishes DQA1*0301 and DQA1*0302. DQA1*0301 was found to be exclusively associated with DQB1*0302, while samples carrying DQB1*0201, 0301, 0303, and 0401 always had DQA1*0302. A few haplotypes carrying DQB1*0302 had DQA1*0302. The fact that DQA1*0301 is completely included in DQB1*0302, and not vice versa, suggests that DQA1*0301 may have arisen from a mutation in a haplotype containing DQA1*0302-DQB1*0302. DQB1*0302 was found to be associated with all DR4 subtypes, suggesting possibly that the current variants of DRB1-DR4 may be of more recent origin. DRB1*0405 was the only subtype of DR4 which was not associated with DQA1*0301 and had multiple associations with the DQB1 alleles, therefore, perhaps representing the oldest allele of this group.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8886.
authors.forename: M A
authors.initials: MA
authors.lastname: Fernandez-Viña
authors.forename: M
authors.initials: M
authors.lastname: Falco
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: M
authors.initials: M
authors.lastname: Cerna
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: E
authors.initials: E
authors.lastname: Raimondi
authors.forename: P
authors.initials: P
authors.lastname: Stastny
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005006:Ethnicity; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D017931:DNA Primers; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes