Noninvasive Prenatal Testing for β-thalassemia by Targeted Nanopore Sequencing Combined with Relative Haplotype Dosage (RHDO): a Feasibility Study

Overview

Journal Sci Rep

Specialty Science

Date 2021 Mar 12

PMID 33707551

Citations 10

Authors

Fuman Jiang

Weiqiang Liu

Longmei Zhang

Yulai Guo

Min Chen

Xiaojing Zeng

Yang Wang

Yufan Li

Jiajia Xian

Bole Du

Yuhuan Xie

Shuming Ouyang

Sheng Li

Yinghong Yang

Chunsheng Zhang

Fei Luo

Xiaofang Sun

Affiliations

Soon will be listed here.

Abstract

Noninvasive prenatal testing (NIPT) for single gene disorders remains challenging. One approach that allows for accurate detection of the slight increase of the maternally inherited allele is the relative haplotype dosage (RHDO) analysis, which requires the construction of parental haplotypes. Recently, the nanopore sequencing technologies have become available and may be an ideal tool for direct construction of haplotypes. Here, we explored the feasibility of combining nanopore sequencing with the RHDO analysis in NIPT of β-thalassemia. Thirteen families at risk for β-thalassemia were recruited. Targeted region of parental genomic DNA was amplified by long-range PCR of 10 kb and 20 kb amplicons. Parental haplotypes were constructed using nanopore sequencing and next generation sequencing data. Fetal inheritance of parental haplotypes was classified by the RHDO analysis using data from maternal plasma DNA sequencing. Haplotype phasing was achieved in 12 families using data from 10 kb library. While data from the 20 kb library gave a better performance that haplotype phasing was achieved in all 13 families. Fetal status was correctly classified in 12 out of 13 families. Thus, targeted nanopore sequencing combined with the RHDO analysis is feasible to NIPT for β-thalassemia.

Citing Articles

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