Comprehensive sequence analysis of HLA-DQA1 and -DQB1 alleles and characterization of DRB1-QAP-DQA1-DQB1 haplotypes |
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Authors: | Shin'ichiro Yasunaga Akinori Kimura and Takehiko Sasazuki |
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Institution: | 1 Department of Genetics, Medical Institute of Bioregulation, Kyushu University Fukuoka Japan 2 Department of Tissue Phisiology, Division of Adult Diseases, Medical Research Institute, Tokyo Medical and Dental University Tokyo Japan |
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Abstract: | It is well known that both chain and β chain of HLA-DQ are highly polymorphic. However the polymorphisms outside the hypervariable region were not fully examined so far. To further clarify the polymorphisms in DQ genes, we determined the nucleotide sequences of full length cDNA, spanning from the leader sequence to the stop codon, from 15 DQA1 alleles and 15 DQB1 alleles. We identified several new DQ alleles which had identical exon 2 sequence and were different in other exons. On the basis of the sequence analyses, a comprehensive PCR-based oligotyping system for DQA1 gene was established. We then characterized DRB1-QAP(DQA1 promoter)-DQA1-DQB1 haplotypes of B-lymphoblastoid cell lines homozygous for HLA and healthy unrelated Japanese and Norwegian populations. It was revealed that DQA1 alleles, which were identical in exon 2 but different in other exons, showed close linkage disequilibrium with diferent characteristic DRB1, QAP and DQB1 alleles. These results suggest that DR-DQ haplotypes have been generated in the early stage of molecular evolution. |
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