TY - JOUR
T1 - DQA1*03 subtypes have different associations with DRB1 and DQB1 alleles
AU - Fernandez-Viña, Marcelo A.
AU - Falco, Michela
AU - Gao, Xiaojian
AU - Cerna, Marie
AU - Sun, Yiping
AU - Raimondi, Eduardo
AU - Stastny, Peter
N1 - Funding Information:
This work was supported in part by National Institutes of Health grants PO1-AI-2327 and RO1 HL47145 and the Texas Advanced Technology Program (grant 003660086) M F was supported in part by Instituto Naztonale per la Rlcerca sul Cancro, Genoa, Italy The authors thank Glenda Gray for assistance in preparing the manuscript
PY - 1994/4
Y1 - 1994/4
N2 - 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.
AB - 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.
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U2 - 10.1016/0198-8859(94)90272-0
DO - 10.1016/0198-8859(94)90272-0
M3 - Article
C2 - 8071103
AN - SCOPUS:0028182193
SN - 0198-8859
VL - 39
SP - 290
EP - 298
JO - Human Immunology
JF - Human Immunology
IS - 4
ER -