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摘要: 地中海贫血又称珠蛋白生成障碍性贫血，是一类具有致死性和致残性的遗传性血液病。地中海贫血目前没有理想的治疗方法，在地中海贫血的防治中，用产前诊断的方式来阻止重型地中海贫血患儿的出生十分重要。地中海贫血目前的基因诊断方式仅能检查出常见的23种突变，而基因测序能对复杂及未知的基因型进行高灵敏度的检测，且已经广泛应用于地中海贫血少见基因型的检测中，在胚胎移植前诊断和无创产前诊断中也有应用。文章基于Sanger、NGS、TGS测序技术的原理、优缺点，对基因测序在地中海贫血诊断中的应用价值做一综述。并基于各代测序的特点，做测序方法选择的建议，作为现行筛查诊断策略的补充。Abstract: Thalassemia, also referred to as globinopathy, is a hereditary blood disorder characterized by its potential lethality and disability. Currently, there is no ideal treatment for thalassemia. In the prevention and treatment of thalassemia, reducing the birth rate of children with severe thalassemia by prenatal diagnosis is particularly important. The existing genetic diagnostic technology for thalassemia can only detect 23 determined common mutations. Gene sequencing can detect complex and unknown genotypes with high sensitivity, and has been widely used in the detection of thalassemia. What's more, it is also used in pre-embryo transfer diagnosis and non-invasive prenatal diagnosis. Based on the principle, advantages and disadvantages of Sanger, NGS and TGS sequencing technology, this paper reviews the application value of gene sequencing in the diagnosis of thalassemia. Above all, the selection of sequencing methods is recommended as a supplement to the current screening and diagnostic strategy.
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Key words:
- thalassemia /
- sequencing technology /
- prenatal diagnosis /
- screening strategy
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表 1 各代测序在地中海贫血检测中的优缺点
测序技术 一代测序 NGS TGS 读长 700~1 000 bp 100~150 bp 高达几十kb 错误率 0.001% ＜1% 13%~20% 数据通量 低 较高 很高 高度同源序列的检测 不准确 不准确 准确 结构变异检出能力 较差 较差 较高 是否需要PCR 需要 需要 不需要 在地中海贫血检测中适用场景 金标准，小片段测序 缺失断点检测 结构变异 
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