Non-invasive prenatal diagnosis and screening for monogenic disorders

Area of Science:

• Genetics
• Molecular Biology
• Bioinformatics

Background:

• Cell-free fetal DNA (cffDNA) is detectable in maternal circulation from 4 weeks gestation.
• Cell-free DNA (cfDNA) analysis from maternal blood enables non-invasive prenatal diagnosis (NIPD), avoiding miscarriage risks of invasive testing.
• NIPD for monogenic diseases has been studied since 2000, with some tests available on the UK NHS since 2012.

Purpose of the Study:

• To review current techniques for NIPD of monogenic diseases.
• To discuss technical challenges and advancements in NIPD methods.
• To highlight the importance of monitoring social and ethical impacts of NIPD.

Main Methods:

• Analysis of cell-free DNA (cfDNA) from maternal blood samples.
• Application of techniques such as next-generation sequencing (NGS) and digital PCR.
• Development of dosage-based techniques for maternally-inherited variants.

Main Results:

• NIPD can provide definitive diagnoses for a wide range of single-gene disorders early in pregnancy.
• Detection of low-level fetal variants in a high maternal DNA background is a key technical challenge.
• Significant progress has been made in overcoming technical limitations for NIPD.

Conclusions:

• NIPD is becoming more widely available through technological advances in both public healthcare and commercial sectors.
• Continued monitoring of the social and ethical implications of NIPD is crucial.
• Ensuring the safety and accuracy of NIPD for patients is paramount.