山东医药2017，Vol.57Issue(7)：23-26,4.DOI:10.3969/j.issn.1002-266X.2017.07.007
1例造血干细胞捐献者HLA新等位基因A*33∶88家系调查及A*33∶88模拟蛋白质三级空间结构分析
Investigation for the heritage of a new HLA allele A * 33 ∶88 in a hematopoietic stem cell donor and analysis of its 3D model structure
摘要
Abstract
Objective To investigate the heritage of a novel human leukocyte antigen (HLA) allele A * 33∶88 in a hematopoietic stem cell donor and to analyze its 3D model structure of HLA molecule.Methods One hematopoietic stem cell donor (proband) and their parents were included,and then,5 mL proband and parental venous blood was collected to detect their blood groups of ABO,Rh red blood cells.We took anticoagulated whole blood 200 μL to extract DNA.Subsequently,HLA typing (HLA-A,HLA-B,HLA-DRB1 site typing) was performed using polymerase chain reaction sequencing-based typing (PCR-SBT).The A * 33∶88 protein 3D structure was constructed by the SWISS-MODEL on the basis of taking the HLA-A * 3α chain with the highest homology as the template to construct,after that,we analyzed the 3D structure of the protein.Results The proband and their parents' blood groups were O-type,Rh blood group was D/CcEe,which was consistent with genetic law.The HLA-A genotype of the donor was A * 11 ∶ 01 and A * 33∶88,the HLA-A genotype of the donor's father was A * 33∶03 and A * 33∶ 03,the HLA-A genotype of the donor's mother was A * 11 ∶ 01 and A * 11∶ 01.The difference between A * 33∶88 and A * 33∶03∶01 was in the third exon at position 475 G ＞ A (codon 135 GCG ＞ ACG),and Gla (A) was changed to Thr (T).We compared the 3D model structure between A * 33∶88 and A * 33∶ 03∶ 01.The encoded amino acid at residue 135 was changed from polar non-polar hydrophobic amino acid (A) to polar hydrophilic amino acid (T).The altered amino acid was located at the α-helix (132-178) position of the antigen peptide binding region,which was the side wall of the antigen polypeptide.Conclusions The new allele A * 33∶88 (HWS10022752) is generated from proband father's mutation,which can be passed to his children.According to its 3D model structure,the amino acid substitution is located in α-helices of antigenic peptide-biding region.关键词
人类白细胞抗原/等位基因/人类白细胞抗原新等位基因/A*33∶88/人类白细胞抗原基因Key words
human leukocyte antigen/alleles/novel allele of human leukocyte antigen/A * 33∶88/human leukocyte antigen gene分类
医药卫生引用本文复制引用
裴永峰,李恒聪,黄惠妮,吴国光..1例造血干细胞捐献者HLA新等位基因A*33∶88家系调查及A*33∶88模拟蛋白质三级空间结构分析[J].山东医药,2017,57(7):23-26,4.基金项目
广西壮族自治区卫生厅科技研究计划项目(Z2010198) （Z2010198）
南宁市科学研究与技术开发计划项目(201003048C-3). （201003048C-3）
