Universal Haplotype-Based Noninvasive Prenatal Testing for Single Gene Diseases.

Area of Science:

• Genetics
• Molecular Biology
• Bioinformatics

Background:

• Noninvasive prenatal testing (NIPT) for single gene diseases is advancing.
• Previous methods for assessing inherited mutations relied on complex parental haplotype analysis or family DNA.
• Linked-read sequencing offers rapid, whole-genome haplotype phasing.

Purpose of the Study:

• To evaluate the feasibility of using linked-read sequencing for noninvasive prenatal testing.
• To develop a streamlined approach for determining fetal mutation status.

Main Methods:

• Parental genome haplotype phasing using linked-read sequencing.
• Identification of single nucleotide polymorphisms (SNPs) in maternal plasma DNA via targeted sequencing.
• Relative haplotype dosage analysis to infer fetal mutation inheritance.

Main Results:

• Successful haplotype phasing in 12 out of 13 families.
• Accurate classification of fetal mutation status for 12 fetuses.
• Demonstrated feasibility of the integrated approach.

Conclusions:

• High-throughput linked-read sequencing combined with maternal plasma analysis provides a streamlined NIPT method.
• This approach eliminates the need for mutation-specific assays and family DNA.
• It is universally applicable for pregnancies at risk of inherited single gene diseases.