类孟买血型基因分析及1种FUT1新无效等位基因的发现

目的 分析类孟买血型基因及H抗原缺乏血型的分子机制,了解FUT1与FUT2基因间的连锁遗传关系.方法 用血清学方法鉴定H抗原缺乏的12名献血者及4名患者的类孟买血型,采用直接测序和克隆测序的方法分析类孟买血型个体的FUT1和FUT2基因.结果 在16名类孟买血型个体者中检出3种已知的FUT1无效等位基因(h1,nt547-552△ag;h2,nt880-882△tt;h3,nt658c→t)和1种新的FUT1无效等位基因(h9,nt424c→t).FUT1基因型分别为h1/h19例,h1/h2 4例,h3/h2、h2/h2及h1/h9各1例.在检出的FUT1无效等位基因中,h1和h2等位基因分别为68.75％(23/32)和21.87％ (7/32).所有FUT2等位基因均存在纯合的nt357c→t同义突变,在具有h2等位基因的个体中,都检出nt716g→a突变(Se357.716);未发现FUT2无效等位基因.结论 发现1种引起H抗原缺乏血型的新FUT1无效等位基因;证实h1和h2为福建地区类孟买血型个体的主要流行基因,支持FUT1和FUT2基因存在连锁遗传的观点.

Analysis of FUT1 and FUT2 genes in 16 para-bombay individuals and identification of a novel null FUT1 allele

Objective To analyze the genetic characteristics of the para-Bombay individuals in Fujian province,and to prove the hypothesis that there is genetic linkage between FUT1 and FUT2.Methods The para-Bombay phenotypes were identified by serological analysis.The sequences of FUT1 and FUT2 gene in para-Bombay individuals were analyzed by direct sequencing and cloning sequencing methods.Results Four null alleles(h1: nt547-552Δag,h2: nt880-882Δtt,h3: nt658c→t,h9: nt424c→t) were observed in 16 para-bombay individuals.The FUT1 genotypes of h1/h1,h1/h2,h3/h2,h2/h2,h1/h9 were detected in 9 individuals,4,1,1,and 1 of 16 individuals,respectively.Two prevalent h alleles,h1 and h2,with the frequency of 68.75%(23/32)and 21.87%(7/32),were predominated in h alleles leading to H deficiency.The mutation of nt357c→t was detected in all FUT2 gene while the mutation of nt716g→a was detected in the individuals with h2 gene.Conclusion A novel h allele(h9) with a nucleotide 424C>T mutation was discovered.The previous observation that h1 and h2 alleles are predominant in H deficient individual in Fujian was confirmed in this study.The fact that the Se357,716 is only found in individual with h2 gene confirms the previous hypothesis that there is genetic linkage between the FUT1 and FUT2.