BGI-Shenzhen, Shenzhen, China.
BGI Genomics, BGI-Shenzhen, Shenzhen, China.
Methods Mol Biol. 2023;2590:287-294. doi: 10.1007/978-1-0716-2819-5_17.
Early prenatal diagnosis of genetic diseases allows for timely intervention or prevention of the diseases in newborns. Conventional prenatal diagnosis of most genetic diseases relies on testing fetal DNA obtained by invasive procedures such as amniocentesis or chorionic villus sampling, which are associated with small risks of fetal loss. Maternal circulating blood contains cell-free DNA (cfDNA) from the fetal genome and can thus be used to noninvasively detect fetal genetic diseases such as chromosomal abnormalities, copy number variants, and single gene diseases. However, due to the presence of a high level of maternal cfDNA in the maternal blood stream, a relative haplotype dosage (RHDO) analysis is required to detect the mutant loci in the fetal genome when performing noninvasive prenatal diagnosis (NIPD) by massively parallel sequencing (MPS) of cfDNA. In this chapter, we describe a protocol utilizing the RHDO strategy for NIPD of any gene of interest associating with single gene diseases.
早期产前诊断遗传疾病可实现对新生儿疾病的及时干预或预防。大多数遗传疾病的常规产前诊断依赖于对通过羊水穿刺或绒毛活检等有创性程序获得的胎儿 DNA 进行检测，这些程序存在导致胎儿丢失的小风险。母体循环血液中含有来自胎儿基因组的无细胞 DNA (cfDNA)，因此可用于非侵入性地检测胎儿遗传疾病，如染色体异常、拷贝数变异和单基因疾病。然而，由于母体血液中存在高水平的母体 cfDNA，因此在利用 cfDNA 的大规模平行测序 (MPS) 进行非侵入性产前诊断 (NIPD) 时，需要进行相对单倍型剂量 (RHDO) 分析以检测胎儿基因组中的突变位点。在本章中，我们描述了一种利用 RHDO 策略对与单基因疾病相关的任何感兴趣基因进行 NIPD 的方案。
