Musfee Fadi I, Oluwafemi Omobola O, Agopian A J, Hakonarson Hakon, Goldmuntz Elizabeth, Mitchell Laura E
Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, 1200 Pressler Street, Houston, TX 77030, USA.
Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
HGG Adv. 2022 Mar 9;3(2):100098. doi: 10.1016/j.xhgg.2022.100098. eCollection 2022 Apr 14.
Maternal effect genes (MEGs) encode factors (e.g., RNA) in the oocyte that control embryonic development prior to activation of the embryonic genome. Over 80 mammalian MEGs have been identified, including several that have been associated with phenotypes in humans. Maternal variation in MEGs is associated with a range of adverse outcomes, which, in humans, include hydatidiform moles, zygotic cleavage failure, and offspring with multi-locus imprinting disorders. In addition, data from both animal models and humans suggest that the MEGs may be associated with structural birth defects such as congenital heart defects (CHDs). To further investigate the association between MEGs and CHDs, we conducted gene-level and gene-set analyses of known mammalian MEGs (n = 82) and two common groups of CHDs: conotruncal heart defects and left ventricular outflow tract defects. We identified 14 candidate CHD-related MEGs. These 14 MEGs include three (, , and ) of the 11 known human MEGs, as well as one () of the eight MEGs that have been associated with structural birth defects in animal models. Our analyses add to the growing evidence that MEGs are associated with structural birth defects, in particular CHDs. Given the large proportion of individuals with structural birth defects for whom etiology of their condition is unknown, further investigations of MEGs as potential risk factors for structural birth defects are strongly warranted.
母体效应基因（MEGs）在卵母细胞中编码控制胚胎基因组激活之前胚胎发育的因子（如RNA）。已鉴定出80多种哺乳动物MEGs，其中包括几种与人类表型相关的基因。MEGs中的母体变异与一系列不良后果相关，在人类中包括葡萄胎、合子分裂失败以及患有多位点印记障碍的后代。此外，来自动物模型和人类的数据表明，MEGs可能与结构性出生缺陷如先天性心脏病（CHDs）有关。为了进一步研究MEGs与CHDs之间的关联，我们对已知的哺乳动物MEGs（n = 82）以及两种常见的CHDs类型：圆锥动脉干心脏缺陷和左心室流出道缺陷进行了基因水平和基因集分析。我们鉴定出14个与CHD相关的候选MEGs。这14个MEGs包括11个已知人类MEGs中的3个（、和），以及在动物模型中与结构性出生缺陷相关的8个MEGs中的1个（）。我们的分析进一步证明了MEGs与结构性出生缺陷，特别是CHDs相关。鉴于很大一部分结构性出生缺陷患者的病因不明，强烈有必要进一步研究MEGs作为结构性出生缺陷潜在风险因素的情况。
