Noninvasive prenatal diagnosis (NIPD) is a risk-free alternative to invasive methods for prenatal diagnosis, e.g. amniocentesis. NIPD is based on the presence of fetal DNA within the mother’s plasma cell-free DNA (cfDNA). Though currently available for various monogenic diseases through detection of point mutations, NIPD is limited to detecting one mutation or up to several genes simultaneously. Noninvasive prenatal whole exome/genome sequencing (WES/WGS) has demonstrated genome-wide detection of fetal point mutations in a few studies. However, Genome-wide NIPD of monogenic disorders currently has several challenges and limitations, mainly due to the small amounts of cfDNA and fetal-derived fragments, and the deep coverage required. Several approaches have been suggested for addressing these hurdles, based on various technologies and algorithms. The first relevant software tool, Hoobari, recently became available. Here we review the approaches proposed and the paths required to make genome-wide monogenic NIPD widely available in the clinic.

非侵入性产前诊断（NIPD）是用于产前诊断的侵入性方法（例如羊膜穿刺术）的无风险替代方案。NIPD基于母亲血浆无细胞DNA（cfDNA）中胎儿DNA的存在。尽管目前通过检测点突变可用于各种单基因疾病，但NIPD限于同时检测一个突变或多达几个基因。无创产前全外显子组/基因组测序（WES / WGS）已在一些研究中证明了对胎儿点突变的全基因组检测。然而，目前，单基因疾病的全基因组全基因组检测存在一些挑战和局限性，这主要是由于少量的cfDNA和胎儿衍生的片段以及所需的深度覆盖。根据各种技术和算法，已经提出了几种解决这些障碍的方法。Hoobari，最近可用。在这里，我们回顾了提出的方法和使全基因组单基因NIPD在临床上广泛可用的途径。