时 间：4月9日16:00
地 点：教学主楼822会议室
主持人：高 灿 教 授
报告人：朱作斌 副教授
题 目：基于核心家系的胚胎发育异常遗传学病因研究
内 容：Embryonic developmental abnormalities (EDAs) are a major cause of miscarriage and congenital disorders, yet over 70% of cases remain unexplained. Here, we present a comprehensive genetic analysis of 567 samples from 236 nuclear families with idiopathic EDAs, integrating whole-exome sequencing (WES), whole-genome sequencing (WGS), and multi-omics approaches. We identified pathogenic single-gene variants in 37.29% of families, including 65 fetal and 23 maternal mutations in known OMIM genes. Additionally, we discovered 13 novel candidate genes (e.g., PEG10, UBR5, ZSWIM1) and two digenic mutation combinations (PATJ+AMOTL2, NDUFA10+NDUFA12) disrupting critical pathways such as RhoA signaling and mitochondrial respiration. Strikingly, embryos exhibited significantly elevated rare mutation burdens (4.2% of families), implicating genome-wide genetic instability as a previously unrecognized contributor. Functional validation via minigene assays and molecular dynamics simulations confirmed splicing defects (PKHD1 c.3592_3628del) and structural perturbations (ACTA1 p.G17S). Our findings expand the genetic architecture of EDAs, provide mechanistic insights into oligogenic and mutational load effects, and establish a framework for precision diagnostics.
