目的研究硫嘌呤甲基转移酶（thiopurine S-methyltransferase，TPMT）基因编码区突变及多态性在急性白血病（acute leukemia，AL）患儿和健康儿童中的分布情况。方法应用逆转录聚合酶链变性梯度凝胶电泳结合DNA直接测序技术，对53例AL...目的研究硫嘌呤甲基转移酶（thiopurine S-methyltransferase，TPMT）基因编码区突变及多态性在急性白血病（acute leukemia，AL）患儿和健康儿童中的分布情况。方法应用逆转录聚合酶链变性梯度凝胶电泳结合DNA直接测序技术，对53例AL患儿和115名健康儿童的cDNAs进行了TPMT突变及多态性的筛查与鉴定，分析各基因型在两组之间的分布差异。结果在健康儿童组TPM丁中发现2个国内外未见报道的基因突变位点：210C〉T（C70C）和622T〉C（F208L）杂合子各1例，提交至GenBankdbsNP，分别获NCBI—SS序列号：107796292、107795933。鉴定了2种已知的编码区单核苷酸多态性（single—nucleotide polymorphisms within the coding region，cSNPs），474T〉C（11581）即TPMT＊1S和719A〉G（T240C）即TPMT＊3C在中国AL患儿及健康儿童中的等位基因频率，分别为14．2％，2．83％与17．0％，3．04％，等位基因总频率分别为16．2％，2．99％。两种cSNPs在两组人群的等位基因频率差异无统计学意义。结论发现了两个新的基因突变位点，提供了为预测不同个体间对硫嘌呤类药物潜在敏感性差异的遗传学标志。确定了两种已知cSNPs在中国AL患儿及健康儿童中的基因型分布和等位基因频率，发现它们与白血病的易感性无相关性。展开更多
Objective: To develop a new method for the detection of TPMT gene mutations and determine the frequencies of four TPMT alleles, TPMT *1, *3A , *3B and *3C in a healthy Chinese population. Methods: A TDI-FP assay syste...Objective: To develop a new method for the detection of TPMT gene mutations and determine the frequencies of four TPMT alleles, TPMT *1, *3A , *3B and *3C in a healthy Chinese population. Methods: A TDI-FP assay system was set up in out lab. To evaluate this system, 220 healthy individuals were analyzed for the polymorphic sites at positions 460(G→A)and 719(A→G)of the TPMP gene using our new TDI–FP method. Results: Three TPMP*3C(G 460→G 719) heterozygotes were identified, TPMP *3A and TPMP *3B were not found. All mutations were confirmed by conventional DNA sequencing analysis. Conclusion: TDI-FP method has proven to be very efficient as a rapid and accurate approach for TPMP genotyping. TPMP *3C was the only polymorphism identified in this clinical samples we have registered.展开更多
文摘目的研究硫嘌呤甲基转移酶（thiopurine S-methyltransferase，TPMT）基因编码区突变及多态性在急性白血病（acute leukemia，AL）患儿和健康儿童中的分布情况。方法应用逆转录聚合酶链变性梯度凝胶电泳结合DNA直接测序技术，对53例AL患儿和115名健康儿童的cDNAs进行了TPMT突变及多态性的筛查与鉴定，分析各基因型在两组之间的分布差异。结果在健康儿童组TPM丁中发现2个国内外未见报道的基因突变位点：210C〉T（C70C）和622T〉C（F208L）杂合子各1例，提交至GenBankdbsNP，分别获NCBI—SS序列号：107796292、107795933。鉴定了2种已知的编码区单核苷酸多态性（single—nucleotide polymorphisms within the coding region，cSNPs），474T〉C（11581）即TPMT＊1S和719A〉G（T240C）即TPMT＊3C在中国AL患儿及健康儿童中的等位基因频率，分别为14．2％，2．83％与17．0％，3．04％，等位基因总频率分别为16．2％，2．99％。两种cSNPs在两组人群的等位基因频率差异无统计学意义。结论发现了两个新的基因突变位点，提供了为预测不同个体间对硫嘌呤类药物潜在敏感性差异的遗传学标志。确定了两种已知cSNPs在中国AL患儿及健康儿童中的基因型分布和等位基因频率，发现它们与白血病的易感性无相关性。
文摘Objective: To develop a new method for the detection of TPMT gene mutations and determine the frequencies of four TPMT alleles, TPMT *1, *3A , *3B and *3C in a healthy Chinese population. Methods: A TDI-FP assay system was set up in out lab. To evaluate this system, 220 healthy individuals were analyzed for the polymorphic sites at positions 460(G→A)and 719(A→G)of the TPMP gene using our new TDI–FP method. Results: Three TPMP*3C(G 460→G 719) heterozygotes were identified, TPMP *3A and TPMP *3B were not found. All mutations were confirmed by conventional DNA sequencing analysis. Conclusion: TDI-FP method has proven to be very efficient as a rapid and accurate approach for TPMP genotyping. TPMP *3C was the only polymorphism identified in this clinical samples we have registered.
