应用高通量测序技术对昆明地区人群珠蛋白生成障碍性贫血基因的筛查研究

目的　探讨昆明地区人群珠蛋白生成障碍性贫血(thalassemia) 基因变异情况，为昆明地区珠蛋白生成障碍性贫血防控工作提供理论依据。方法　对2018 年昆明市政府“十大惠民项目”中25 家医疗机构收集的5 787 例婚前、孕前优生及健康体检样本采用高通量测序技术检测，进行珠蛋白生成障碍性贫血基因（α+β）301 型筛查应用情况分析。结果　①通过高通量测序检测发现，在5 787 例样本中，共检出465 例阳性，阳性率为8.04%。其中α- 检出285 例，β-检出131 例，复合型检出10 例，异常血红蛋白变异类型检出17 例，其他变异型检出22 例。② α- 珠蛋白生成障碍性贫血携带者检出285 例，以-α3.7/αα 基因型最为常见，为152 例（53.33%）。β- 珠蛋白生成障碍性贫血携带者检出131 例，以Hb E 杂合子、Codon 17(A ＞ T) 基因型最为常见，各占26.72%；③ αβ 复合型珠蛋白生成障碍性贫血变异类型检出10 例，占2.15%；异常血红蛋白变异类型检出17 例，占3.66%；检出其他变异型22 例，占4.73%。结论　昆明地区人群珠蛋白生成障碍性贫血变异基因类型较为复杂，高通量测序技术可更全面检测珠蛋白生成障碍性贫血变异基因类型。

Study on Screening of Thalassemia Genes by Next-generation Sequencing in Kunming Area

Objective　To explore the variations of thalassemia genes in Kunming and provide theoretical basis for prevention and control. Methods　5 787 samples of pre marriage, pre pregnancy healthy birth testing and healthy physical examination population, which from 25 medical institutions in Kunming with thalassemia gene (α+β) 301 types were screened by Nextgeneration sequencing technology in the “Ten Projects Benefiting the People” of Kunming government in 2018, and the clinical data were analyzed by bioinformatics and statistical analysis. Results　① Through high-throughput Sequencing, 465 out of 5 787 samples were positive, with a positive rate of 8.04%, and among them, 285 cases of α-thalassemia, 131 cases of β thalassemia, 10 cases of compound type, 17 cases of abnormal hemoglobin variation and 22 cases of other variations were detected. ② There were 285 cases of α-thalassemia and 152 cases (53.33%) were most common with -α3.7/αα genotype. A total of 131 cases of β-thalassemia were detected, and Hb E heterozygote and Codon 17(A ＞ T) genotype were the most common, accounting for 26.72% respectively. ③ There were 10 cases (2.15%) of the variation types of α/β-complex thalassemia. 17 cases (3.66%) abnormal hemoglobin variation were detected, and 22 cases (4.73%) of other variants were detected. Conclusion　The carriers rate of thalassemia in Kunming was 8.04%. Due to the variation gene types of thalassemia were more complex, Next-generation sequencing can detect rare thalassemia variation gene types more comprehensively.