Haplotype-based approach for noninvasive prenatal tests of Duchenne muscular dystrophy using cell-free fetal DNA in maternal plasma
Haplotype-based approach for noninvasive prenatal tests of Duchenne muscular dystrophy using cell-free fetal DNA in maternal plasma
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DOI：
10.1038/gim.2014.207
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发表时间：
2015-11-01
影响因子：
8.8
通讯作者：
Ji, Xing
中科院分区：
文献类型：
--
作者：
Xu, Yan;Li, Xuchao;Ji, Xing
目的：这项研究表明非侵入性产前检测（NIPT）杜氏肌营养不良症（DMD）使用新开发的单倍型为基础的approach.Methods：8个家庭在DMD的风险被招募为这项研究。父母的单倍型构建使用的目标区域测序数据从父母和先证者。通过母体血浆DNA测序，使用隐马尔可夫模型构建胎儿单倍型。在男性中，与母体突变等位基因连锁的单倍型的存在表明胎儿受影响。通过比较单核苷酸多态性（SNP）基因型推断胎儿基因组DNA的直接测序结果进一步验证了该方法。产前诊断证实与子宫颈穿刺术，这些结果被解释在一个盲fashion.Results：结果显示，平均准确率为99.98%的总推断母体SNPs。与平均深度为30倍，在每个样品的10 Mb的目标区域实现，非侵入性的结果是一致的，与侵入性proceeding.Conclusion：这是第一次报告的NIPT DMD和第一次应用的单倍型为基础的方法在NIPT的X连锁疾病。随着准确性的进一步提高，这种基于单体型的策略可能适用于DMD甚至其他X连锁单基因疾病的NIPT。
Purpose: This study demonstrates noninvasive prenatal testing (NIPT) for Duchenne muscular dystrophy (DMD) using a newly developed haplotype-based approach.Methods: Eight families at risk for DMD were recruited for this study. Parental haplotypes were constructed using target-region sequencing data from the parents and the probands. Fetal haplotypes were constructed using a hidden Markov model through maternal plasma DNA sequencing. The presence of haplotypes linked to the maternal mutant alleles in males indicated affected fetuses. This method was further validated by comparing the inferred single-nucleotide polymorphism (SNP) genotypes to the direct sequencing results of fetal genomic DNA. Prenatal diagnosis was confirmed with amniocentesis, and those results were interpreted in a blinded fashion.Results: The results showed an average accuracy of 99.98% for the total inferred maternal SNPs. With a mean depth of 30x achieved in the 10-Mb target region of each sample, the noninvasive results were consistent with those of the invasive procedure.Conclusion: This is the first report of NIPT for DMD and the first application of a haplotype-based approach in NIPT for X-linked diseases. With further improvements in accuracy, this haplotype-based strategy could be feasible for NIPT for DMD and even other X-linked single-gene disorders.