Author:
Chen Chao,Chen Min,Zhu Yaping,Jiang Lu,Li Jia,Wang Yaoshen,Lu Zhe,Guo Fengyu,Wang Hairong,Peng Zhiyu,Yang Yun,Sun Jun
Abstract
Abstract
Background
Though massively parallel sequencing has been widely applied to noninvasive prenatal screen for common trisomy, the clinical use of massively parallel sequencing to noninvasive prenatal diagnose monogenic disorders is limited. This study was to develop a method for directly determining paternal haplotypes for noninvasive prenatal diagnosis of monogenic disorders without requiring proband’s samples.
Methods
The study recruited 40 families at high risk for autosomal recessive diseases. The targeted linked-read sequencing was performed on high molecular weight (HMW) DNA of parents using customized probes designed to capture targeted genes and single-nucleotide polymorphisms (SNPs) distributed within 1Mb flanking region of targeted genes. Plasma DNA from pregnant mothers also underwent targeted sequencing using the same probes to determine fetal haplotypes according to parental haplotypes. The results were further confirmed by invasive prenatal diagnosis.
Results
Seventy-eight parental haplotypes of targeted gene were successfully determined by targeted linked-read sequencing. The predicted fetal inheritance of variant was correctly deduced in 38 families in which the variants had been confirmed by invasive prenatal diagnosis. Two families were determined to be no-call.
Conclusions
Targeted linked-read sequencing method demonstrated to be an effective means to phase personal haplotype for noninvasive prenatal diagnosis of monogenic disorders.
Funder
the National Natural Science Foundation of China
the National Key Research and Development Program of China
Major Technical Innovation Project of Hubei Province
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics
Cited by
10 articles.
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