Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locus
[Objective] To study the inter-allelic recombination event occurring in the HLA-B locus, and to evaluate the molecular genetic mechanisms of a novel HLA allele, predict and analyze the impact of its amino acid residue changes on the three-dimensional structure. [Methods] HLA typing was taken with po...
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Institute of Blood Transfusion of Chinese Academy of Medical Sciences
2025-03-01
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| Series: | Zhongguo shuxue zazhi |
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| Online Access: | https://www.cjbt.cn/thesisDetails#10.13303/j.cjbt.issn.1004-549x.2025.03.004&lang=en |
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| _version_ | 1849760879456813056 |
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| author | ZHANG Xu LIN Fengqiu LI Xiaofeng LI Jianping |
| author_facet | ZHANG Xu LIN Fengqiu LI Xiaofeng LI Jianping |
| author_sort | ZHANG Xu |
| collection | DOAJ |
| description | [Objective] To study the inter-allelic recombination event occurring in the HLA-B locus, and to evaluate the molecular genetic mechanisms of a novel HLA allele, predict and analyze the impact of its amino acid residue changes on the three-dimensional structure. [Methods] HLA typing was taken with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) by Luminex. Sequence-based typing (SBT) and gene clone were used to analyze exons 1-4 sequences of HLA-B allele. In order to determine the exact site of inter-allelic recombination event occurring in the HLA-B locus, sequences of the HLA-B alleles were compared with the IMGT/HLA database by the program “Alignment”. After homology modeling using the Swiss-Model software, the three-dimensional structure of the molecules was simulated using the Swiss Pdb Viewer software, and the FATCAT online software was used to compare the differences in the three-dimensional structures of the molecules. [Results] HLA typing indicated the PCR-SSOP pattern did not match with any known HLA-B alleles, suspected to be a new HLA allele. The genetic clone sequencing results showed HLA-B alleles of the proband were B*13∶02 and a novel allele. The HLA-B exon2 nucleotide sequence of the novel allele was different from any other known alleles. The novel allele has 12 nucleotides replaced when compared with the closest matching B*35∶01∶01∶01 allele from c.259 to c.299, which result in 8 amino acids changes. The sequence was identical in B*35∶01∶01∶01 in exon 1, exon 3, exon 4, intron 1, intron 2, intron 3 and at c.74 to c.258 in exon 2, and c.259 to c.343 sequence in exon 2 was identical in B*46∶01∶01 by blast search. The structure of the mutant alleles was similar to that of B*35∶01∶01∶01 and B*46∶01∶01, and the local hydrogen bonds of amino acids p.63-p.79 were changed at the recombination site. [Conclusion] This study demonstrates a rare inter-allelic recombination event occurring in the HLA-B locus. It has been officially designated as HLA-B*35∶186 by WHO Nomenclature Committee for Factors of the HLA System. It illustrates the process of novel allele, and provides new evidence for the further studying mechanisms of gene recombination and HLA polymorphism. |
| format | Article |
| id | doaj-art-079fa79648ed4e709265c4d7de4dc310 |
| institution | DOAJ |
| issn | 1004-549X |
| language | zho |
| publishDate | 2025-03-01 |
| publisher | Institute of Blood Transfusion of Chinese Academy of Medical Sciences |
| record_format | Article |
| series | Zhongguo shuxue zazhi |
| spelling | doaj-art-079fa79648ed4e709265c4d7de4dc3102025-08-20T03:06:13ZzhoInstitute of Blood Transfusion of Chinese Academy of Medical SciencesZhongguo shuxue zazhi1004-549X2025-03-0138332232610.13303/j.cjbt.issn.1004-549x.2025.03.0041004-549X(2025)3-0322-06Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locusZHANG Xu0LIN Fengqiu1LI Xiaofeng2LI Jianping3Institute of Transfusion Medicine, Shenyang Central Blood Station (Liaoning Blood Center), Shenyang 110044, ChinaInstitute of Transfusion Medicine, Shenyang Central Blood Station (Liaoning Blood Center), Shenyang 110044, ChinaInstitute of Transfusion Medicine, Shenyang Central Blood Station (Liaoning Blood Center), Shenyang 110044, ChinaInstitute of Transfusion Medicine, Shenyang Central Blood Station (Liaoning Blood Center), Shenyang 110044, China[Objective] To study the inter-allelic recombination event occurring in the HLA-B locus, and to evaluate the molecular genetic mechanisms of a novel HLA allele, predict and analyze the impact of its amino acid residue changes on the three-dimensional structure. [Methods] HLA typing was taken with polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) by Luminex. Sequence-based typing (SBT) and gene clone were used to analyze exons 1-4 sequences of HLA-B allele. In order to determine the exact site of inter-allelic recombination event occurring in the HLA-B locus, sequences of the HLA-B alleles were compared with the IMGT/HLA database by the program “Alignment”. After homology modeling using the Swiss-Model software, the three-dimensional structure of the molecules was simulated using the Swiss Pdb Viewer software, and the FATCAT online software was used to compare the differences in the three-dimensional structures of the molecules. [Results] HLA typing indicated the PCR-SSOP pattern did not match with any known HLA-B alleles, suspected to be a new HLA allele. The genetic clone sequencing results showed HLA-B alleles of the proband were B*13∶02 and a novel allele. The HLA-B exon2 nucleotide sequence of the novel allele was different from any other known alleles. The novel allele has 12 nucleotides replaced when compared with the closest matching B*35∶01∶01∶01 allele from c.259 to c.299, which result in 8 amino acids changes. The sequence was identical in B*35∶01∶01∶01 in exon 1, exon 3, exon 4, intron 1, intron 2, intron 3 and at c.74 to c.258 in exon 2, and c.259 to c.343 sequence in exon 2 was identical in B*46∶01∶01 by blast search. The structure of the mutant alleles was similar to that of B*35∶01∶01∶01 and B*46∶01∶01, and the local hydrogen bonds of amino acids p.63-p.79 were changed at the recombination site. [Conclusion] This study demonstrates a rare inter-allelic recombination event occurring in the HLA-B locus. It has been officially designated as HLA-B*35∶186 by WHO Nomenclature Committee for Factors of the HLA System. It illustrates the process of novel allele, and provides new evidence for the further studying mechanisms of gene recombination and HLA polymorphism.https://www.cjbt.cn/thesisDetails#10.13303/j.cjbt.issn.1004-549x.2025.03.004&lang=enhla-b antigenb*35∶186gene recombinationsequence analysisanalysis of protein three-dimensional structure |
| spellingShingle | ZHANG Xu LIN Fengqiu LI Xiaofeng LI Jianping Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locus Zhongguo shuxue zazhi hla-b antigen b*35∶186 gene recombination sequence analysis analysis of protein three-dimensional structure |
| title | Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locus |
| title_full | Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locus |
| title_fullStr | Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locus |
| title_full_unstemmed | Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locus |
| title_short | Sequence and protein three-dimensional structure analysis of a novel inter-allelic recombination allele B*35∶186 of HLA-B locus |
| title_sort | sequence and protein three dimensional structure analysis of a novel inter allelic recombination allele b 35∶186 of hla b locus |
| topic | hla-b antigen b*35∶186 gene recombination sequence analysis analysis of protein three-dimensional structure |
| url | https://www.cjbt.cn/thesisDetails#10.13303/j.cjbt.issn.1004-549x.2025.03.004&lang=en |
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