THE DQA1-ASTERISK-0104 ALLELE IS CARRIED BY DRB1-ASTERISK-1001-POSITIVE AND DRB1-ASTERISK-1401-POSITIVE HAPLOTYPES IN CAUCASIANS, AFRICANS AND ORIENTALS

The DQA10104 allele is known to differ from DQA1*0101 by a single nuc leotide in the sequenced part of the first exon. DQA10104 has a guani ne in the second position of the second expressed codon, whereas DQA1 0101 and all other sequenced DQA1 alleles have an adenine in that posi tion, changing aspartic acid to glycine. The DQA10104 allele was orig inally described in African Americans with the DRB112, DRB3*0101, DQA 10104, DQB1*0501, DRB1*12, DRB3*0202, DQA1*0104, DQB1*0605 or DRB1*14 , DQA10104, DQB1*0503 haplotypes. When developing DQA1 typing by PCR amplification with sequence-specific primers (PCR-SSP), we observed th at all DR10- and DR14-positive samples carried the DQA10104 allele, w heres all DRB101-positive DNAs carried the closely related DQA1*0101 allele. In the present study, samples representing the major ethnic gr oups with DR-DQ haplotypes known to carry the DQA10104 allele or the very similar DQA10101 allele were investigated by TaqI RFLP analysis, PCR-SSP typing and nucleotide sequencing. The DQA10104 allele was fo und to differ from DQA10101 not only in the second expressed codon, b ut also by a productive mutation in the signal peptide. All investigat ed DRB11001-(n=24) and DRB1*1401-positive (n=25) haplotypes, defined by homozygosity or association, of Caucasian, African or Oriental orig in carried the DQA10104 allele, whereas the DQA1*0101 allele was foun d on all DRB101-positive (n=32) haplotypes. These findings demonstrat e that in the assignment of HLA class II alleles, polymorphism outside the second exon sometimes must be considered. The maintenance of the DQA10104 allele on a few distinct haplotypes indicates that the allel e is old and might also be compatible with a functional difference bet ween the DQA10101 and DQA1*0104 alleles.