DNA plays a crucial role in human growth and development. Irreparable DNA damage caused by external environmental factors leads to disease, which may be transmitted to future generations through genetic material. Common genetic disorders in humans can be divided into four broad categories: chromosomal, monogenic, polygenic, and mitochondrial disorders. While most single gene disorders are rare, their wide variety results in a cumulative overall incidence of 2% – 3%.

Prevention and Control of Single Gene Disorders 

The prevention and control of single-gene disorders takes place at three stages:

1. Preconception: Genetic counseling and PGT-M can help prevent and control genetic disorders. However, PGT-M is costly and complex, and prenatal diagnosis is generally still required after PGT-M.

2. Prenatal: For women with abnormal ultrasound or serum screening results, invasive prenatal diagnosis is still required (e.g., chorionic villus sampling, amniocentesis, cordocentesis), which is associated with approximately 1% risk of miscarriage.

3. Newborn: Newborn genetic screening is conducted after birth for early prevention.

Non-Invasive Prenatal Testing for Single Gene Disorders 

With advances in sequencing technology, researchers and healthcare professionals have identified ways to utilize cell-free fetal DNA in early screening of single gene disorders to facilitate early detection and intervention. A variety of techniques, including microarrays, digital PCR, RT-PCR, relative mutation dosage (RMD), relative haplotype dosage (RHDO) analysis, and high-throughput sequencing (NIPT-SGD), have been developed for early non-invasive screening of single gene disorders. RHDO analysis and NIPT-SGD perform well for de novo mutation detection as they do not rely on variant-specific testing.

RHDO analysis is a complex process that utilizes single nucleotide polymorphisms (SNPs) to phase the haplotypes of a proband and identify the maternal and paternal haplotypes linked with high-risk alleles. cfDNA sequencing data is then analyzed to phase fetal haplotypes and determine whether the fetus has inherited the high-risk allele. In contrast, NIPT-SGD directly interrogates key coding exons, introns, and intron/exon boundaries through targeted capture and NGS of the pregnant woman’s cfDNA. It is capable of detecting 1 – 100 disorders in a single test and does not require paternal genetic information, providing higher throughput and sensitivity than traditional tests.

NIPT-SGD vs. NIPT

Non-invasive prenatal testing (NIPT) and NIPT for single gene disorders (NIPT-SGD) both use cfDNA for testing, but there are differences in the methodologies they adopt. NIPT-SGD tests for mutations in exons, intron/exon boundaries, and important introns. The two commonly used tests, NIPT and NIPT Plus, are both based on low-depth whole-genome sequencing and are only capable of detecting chromosomal copy number abnormalities in the fetus. To detect smaller chromosomal microdeletions/microduplications, higher sequencing depth is required, which is usually achieved by targeted enrichment.

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Vazyme is committed to providing reliable materials for library preparation and capture reagents for our customers. By staying abreast of the latest advances in reproductive health, we assist in promoting prenatal and postnatal care.

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