Exploring epigenomic mechanisms of neural tube defects using multi‐omics methods and data

Abstract

Neural tube defects (NTDs) are a heterogeneous set of malformations attributed to disruption in normal neural tube closure during early embryogenesis. An in-depth understanding of NTD etiology and mechanisms remains elusive, however. Among the proposed mechanisms, epigenetic changes are thought to play an important role in the formation of NTDs. Epigenomics covers a wide spectrum of genomic DNA sequence modifications that can be investigated via high-throughput techniques.Recent advances in epigenomic technologies have enabled epigenetic studies of congenital malformations and facilitated the integration of big data into the understanding of NTDs. Herein, we review clinical epigenomic data that focuses on DNA methylation, histone modification, and miRNA alterations in human neural tissues, placental tissues, and leukocytes to explore potential mechanisms by which candidate genes affect human NTD pathogenesis. We discuss the links between epigenomics and gene regulatory mechanisms, and the effects of epigenetic alterations in human tissues on neural tube closure.

Anencephaly in Slovakia and Czech Republic: embryogenesis, risk factors, epidemiology and preventative approaches

“…Moreover, investigators will need to integrate genetic data with information on epigenetic, environmental, and nutritional factors to obtain a more comprehensive understanding of the causes of individual NTDs (118). Advances in whole-genome sequencing, exome-whole sequencing, and next-generation sequencing may help researchers in beginning to comprehend the genetic and epigenetic basis of NTDs in humans (119,120). The use of proteomics and other "omics" technology can propel the identification of novel biomarkers and molecular networks implicated in NTDs, which is an indispensable step in the improvement of patient management (121,122).…”