优选短串联重复序列应用于脊肌萎缩症产前诊断的连锁分析

目的建立完整的适合汉族人群的脊肌萎缩症（SMA）产前基因诊断体系。方法对30名正常汉族人的外周血样本进行基因多态性分析,评估位于运动神经元存活基因1（SMN1）两侧的短串联重复序列（STR）位点的多态信息含量;并通过在6个SMA产前诊断家系连锁中的应用,优选出STR位点,并结合PCR酶-切法（PCR-RFLP）进一步评价STR位点与SMN1基因的连锁紧密性。结果从7个STR位点中优选出D5S435、D5S629、D5S610和D5S351四个STR位点用于家系连锁分析,联合PCR-RFLP,在6名待检胎儿中检出2例患者和4例携带者。结论通过优选出的4个多态性强、与SMN1基因紧密连锁的STR位点,联合家系连锁和PCR-RFLP,建立起稳定可靠的适合汉族人群的SMA产前基因诊断体系。

Selection of short tandem repeats and their application in linkage analysis for prenatal diagnosis of spinal muscular atrophy

Objective To establish a solid prenatal genetic diagnosis system for spinal muscular atrophy (SMA) in Chinese Han populations. Methods Gene polymorphism analysis was conducted with peripheral blood samples of 30 Chinese Han normal people, and polymorphic informative content of short tandem repeats (STR) loci linking to survival motor neuron gene 1(SMN1) was assessed. Appropriate STR loci were selected by linkage analysis of prenatal diagnosis of 6 Chinese SMA families, and PCR-restriction fragment length polymorphism (PCR-RFLP) assay was employed to evaluate the linkage between STR loci and SMN1. Results Four out of the 7 STR loci, D5S435, D5S629, D5S610 and D5S351 were selected for linkage analysis, and 2 affected fetuses and 4 carriers were detected in 6 SMA families with PCR-RFLP assay. Conclusion A solid and reliable SMA prenatal diagnosis system is established, which combines PCR-RFLP assay with linkage analysis using 4 selected STR loci suitable for Chinese Han populations.