血型B(A)亚型的鉴定及家系分析  

Identification of B(A)subtype and family analysis

作　　者：邹陆辰 吴雪纯 周笑妍 李梦楠 张睿 吴欢 杜振军 孙恩涛 ZOU Luchen;WU Xuechun;ZHOU Xiaoyan;LI Mengnan;ZHANG Rui;WU Huan;DU Zhenjun;SUN Entao(Labora-tory of Health Inspection,School of Public Health,Wannan Medical College,Wuhu 241002,China;Department of Health Inspection and Quarantine,School of Inspection,Wannan Medical College;Laboratory Department,Liaocheng Blood Station)

机构地区：[1]皖南医学院公共卫生学院卫生检验学实验室,芜湖241002 [2]皖南医学院检验学院卫生检验与检疫学教研室 [3]聊城市中心血站检验科

出　　处：《山西医科大学学报》2024年第11期1474-1479,共6页Journal of Shanxi Medical University

摘　　要：目的 对ABO血型血清学鉴定异常的1例受试者进行血型鉴定及家系分析,为解决疑难血型的鉴定及遗传规律提供科学依据。方法 在常规血清学鉴定基础上,使用序列特异引物引导的聚合酶链反应(PCR-SSP)扩增受试者外周血ABO基因的6、7外显子,使用Sanger测序分析先证者及子女的血型基因型并调查家系。构建3D分子结构模型,预测突变后的半乳糖基转移酶(Cgt B)的热力学稳定性(△△G)、不稳定系数以及分子间作用力(范德华力)进行预测。结果 先证者血清学表型符合B(A)或A_(W)B亚型;女儿血清学表型符合cis AB或AB_(3);儿子血清学表型符合A型。先证者与其女儿正反定型不符。将3名受试者血型的测序结果与标准序列A101比对,先证者7号外显子存在c.700C>G且6号外显子存在c.261del G,基因型为ABO*B(A)。02/ABO*O.01.13;女儿7号外显子存在c.700C>G且存在c.467C>T,基因型为ABO*B(A)。02/ABO*A1.02;儿子7号外显子存在c.467C>T且6号外显子存在c.261del G,基因型为ABO*A1.02/ABO*O.01.13。分子建模与分析提示突变后Cgt B的??G为负值,不稳定系数较高且突变后其结构丢失2个碳原子。结论 当标准血型血清学ABO血型正反定型不符时,利用分子生物学检测技术可以确定血型基因型弥补血清学方法的不足。根据本研究构建的生物信息学模型预测突变后的Cgt B为不稳定蛋白,可能导致其B(A)亚型表现型。通过生物信息学模型可以揭示罕见ABO亚型的血清学表型、基因型的特点及遗传规律,为临床输血提供保障。Objective To investigate the blood group typing and pedigree analysis of a subject with abnormal serological identification of ABO blood group for providing scientific basis in the identification and the genetic law of difficult blood group.Methods On the basis of routine serological identification,the exons 6 and 7 of ABO gene in peripheral blood were amplified by polymerase chain reac-tion(PCR-SSP)guided by sequence specific primers and sequenced,and a 3D molecular structure model was constructed to predict the thermodynamic stability(∆∆G),instability coefficient and intermolecular force(van der Waals force)of mutated galactosyltransfe-rase(CgtB).Results The serological phenotype of the proband conformed to B(A)or AWB subtype,the daughter serophenotype conformed to cisAB or AB_(3),and the son serophenotype conformed to A.The proband and his daughter did not match the positive and negative stereotypes.Compared with the standard sequence A101,the proband had c.700C>G in exon 7 and c.261delG in exon 6 with a genotype of ABO*B(A).02 and ABO*01.13,his daughter had c.700C>G and c.467C>T in exon 7 with a genotype of ABO*B(A).02/ABO*A1.02,and his son had c.467C>T in exon 7 and c.261delG in exon 6 with a genotype of ABO*A1.02/ABO*O.01.13.Molecular modeling and analysis showed that the∆∆G of CgtB was negative,the instability index was higher and two carbon atoms were lost after mutation.Conclusion When the positive and negative ABO blood typing results in standard serological tests are not matched,mo-lecular biology testing techniques can be employed to ascertain the blood group genotype for making up for the limitations of serological methods.According to the bioinformatics model developed in this study,it is predicted that the mutated CgtB protein is unstable and potentially results in the expression of the B(A)subtype phenotype.Bioinformatics models can be used to uncover the serological phe-notypes,genotype characteristics,and genetic patterns of rare ABO subtypes for ensuring safety in clinical blood transfu

关 键 词：ABO亚型 血型鉴定 交叉配血 家系调查 B(A)亚型 CgtB 血型鉴定 生物信息学 

分 类 号：R457.1[医药卫生—治疗学]