Objective: To investigate the identification and molecular biological mechanism of a case of B(A)04 allele.
Methods: The ABO blood groups of the proband and his nine family members were analyzed serologically and DNA sequencing was used to accurately determine the genotypes of these ten specimens. The cartoon models of local active center of enzymes of the GTA,GTB and the GTB mutant were constructed to explore the possible molecular mechanism leading to abnormal enzyme-catalyzed A antigen synthesis.
Results: The serological results suggested that the ABO blood groups of the proband, his elder brother and his maternal grandmother were AweakB or B(A); the ABO blood group of his mother was type AB, his uncle and elder aunt were type B, and his father was type O. ABO blood group gene sequencing results showed that 6 out of 10 members of the family carried the B(A)04 allele. Molecular structure models suggested that the spatial distance of critical amino acid residues in the catalytic center of the GTB mutant enzyme was greater than that of GTB, which might cause the enzyme to abnormally catalyze the synthesis of A antigen.
Conclusion: The characteristics of serological reactions of B(A) blood subgroup are complicated, and its identification needs to be combined with molecular biology and pedigree investigation. It is speculated that the B(A) phenotype may be associated with a larger volume of the catalytic center in the GTB mutant.
题目: B(A)04等位基因的鉴定及相关分子机制.
目的: 探讨B(A)04等位基因的鉴定及相关分子生物学机制.
方法: 采用血型血清学法、基因测序法鉴定先证者及其9名亲属的ABO血型，分析血清学反应特点及家系遗传规律；构建突变体酶催化中心的局部空间模型，探索导致酶异常催化A抗原合成的可能分子机制.
结果: 血清学结果提示先证者及其哥哥、外祖母表型为AweakB或B(A)；其母亲表型为AB型，其舅舅及大姨为B型，其父亲为O型。ABO血型基因测序结果表明，该家系10名成员中，有6名携带B(A)04等位基因。分子结构模型显示，GTB突变体酶催化中心关键氨基酸残基的空间距离大于GTB，可能是引起酶异常催化A抗原合成的原因.
结论: B(A)亚型血清学反应存在差异，其鉴定需与分子生物学及家系调查结合来判定。推测B(A)表现型可能与GTB突变体的催化中心容积变大有关.
Keywords: ABO blood group; B(A) subtype; gene sequencing; molecular model; pedigree investigation.