Synthetic mismatches enable specific CRISPR-Cas12a-based detection of genome-wide SNVs tracked by ARTEMIS.

Detection of pathogenic DNA variants is vital in cancer diagnostics and treatment monitoring. While CRISPR-based diagnostics (CRISPRdx) offer promising avenues for cost-effective, rapid, and point-of-care testing, achieving single-nucleotide detection fidelity remains challenging. We present an in silico pipeline that scans the human genome for targeting pathogenic mutations in the seed region (ARTEMIS), the most stringent crRNA domain.

Fetal Fraction of Cell-Free DNA in the Prediction of Adverse Pregnancy Outcomes: A Nationwide Retrospective Cohort Study.

Objective: To assess the added value of fetal fraction of cell-free DNA in the maternal circulation in the prediction of adverse pregnancy outcomes.

Design: Retrospective cohort study.

Setting: Nationwide implementation study on non-invasive prenatal testing (NIPT; TRIDENT-2 study).

GWAS shows the genetics behind cell-free DNA and highlights the importance of p.Arg206Cys in DNASE1L3 for non-invasive testing.

The properties of cell-free DNA (cfDNA) are intensely studied for their potential as non-invasive biomarkers. We explored the effect of common genetic variants on the concentration and fragmentation properties of cfDNA using a genome-wide association study (GWAS) based on low-coverage whole-genome sequencing data of 140,000 Dutch non-invasive prenatal tests (NIPTs). Our GWAS detects many genome-wide significant loci, functional enrichments for phagocytes, liver, adipose tissue, and macrophages, and genetic correlations with autoimmune and cardiovascular disease.

Implementing non-invasive prenatal testing in a national screening program: Lessons learned from the TRIDENT studies.

The Dutch NIPT Consortium, a multidisciplinary collaboration of stakeholders in prenatal care initiated and launched the TRIDENT studies. The goal of the TRIDENT studies was to implement non-invasive prenatal testing (NIPT), first as a contingent (second-tier) and later as a first-tier test, and to evaluate this implementation. This paper describes how NIPT can be successfully implemented in a country or state.