A Cell‐free DNA Barcode‐Enabled Single‐Molecule Test for Noninvasive Prenatal Diagnosis of Monogenic Disorders: Application to β‐Thalassemia

• DOI: 10.1002/advs.201802332
• Publication Date: 2019-04-01T10:12:58Z
• Authors: Xingkun Yang; Qinghua Zhou; Wanjun Zhou; Mei Zhong; Xiaoling Guo; Xiaofeng Wang; Xin Fan; Shanhuo Yan; Liyan Li; Yunli Lai; Yongli Wang; Jin Huang; Yuhua Ye; Huaping Zeng; Jun Chuan; Yuanping Du; Chouxian Ma; Peining Li; Zhuo Song; Xiangmin Xu
• Keywords: Cell-free fetal DNA; Beta thalassemia

Noninvasive prenatal testing of common aneuploidies has become routine over the past decade, but monogenic disorders remains a challenge in clinical implementation. Most recent studies have inherent limitations, such as complicated procedures, lack versatility, and need for prior knowledge parental genotypes or haplotypes. To overcome these robust versatile next-generation sequencing-based cell-free DNA (cfDNA) allelic molecule counting system termed cfDNA barcode-enabled single-molecule test (cfBEST) is developed noninvasive diagnosis (NIPD) disorders. The accuracy cfBEST found to be comparable that droplet digital polymerase chain reaction (ddPCR) detecting low-abundance mutations cfDNA. analytical validity evidenced by β-thalassemia assay, which blind validation study 143 at-risk pregnancies reveals sensitivity 99.19% specificity 99.92% on allele detection. Because validated method can used detect maternal-fetal genotype combinations precisely quantitatively, it holds potential NIPD human