Every year nearly 6 percent of children worldwide are born with a serious congenital malformation, resulting in death or lifelong disability. In the United States, birth defects remain one of the leading causes of infant mortality. Among the common structural congenital defects are conditions known as neural tube defects (NTDs). These are a class of malformation of the brain and spinal cord where the neural tube fails to close during the neurulation. Although NTDs remain among the most pervasive and debilitating of all human developmental anomalies, there is insufficient understanding of their etiology. Previous studies have proposed that complex birth defects like NTDs are likely omnigenic, involving interconnected gene regulatory networks with associated signals throughout the genome. Advances in technologies have allowed researchers to more critically investigate regulatory gene networks in ever increasing detail, informing our understanding of the genetic basis of NTDs. Employing a systematic analysis of these complex birth defects using massively parallel DNA sequencing with stringent bioinformatic algorithms, it is possible to approach a greater level of understanding of the genomic architecture underlying NTDs. Herein, we present a brief overview of different approaches undertaken in our laboratory to dissect out the genetics of susceptibility to NTDs. This involves the use of mouse models to identify candidate genes, as well as large scale whole genome/whole exome (WGS/WES) studies to interrogate the genomic landscape of NTDs. The goal of this research is to elucidate the gene‐environment interactions contributing to NTDs, thus encouraging global research efforts in their prevention.

中文翻译：

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研究复杂出生缺陷基因组结构的方法。

全球每年有近 6% 的儿童出生时患有严重的先天性畸形，导致死亡或终生残疾。在美国，出生缺陷仍然是婴儿死亡的主要原因之一。在常见的结构先天性缺陷中，有一种称为神经管缺陷 (NTD) 的疾病。这些是大脑和脊髓的一类畸形，神经管在神经形成过程中无法关闭。尽管 NTD 仍然是所有人类发育异常中最普遍和最使人衰弱的，但对其病因的了解不足。先前的研究表明，像 NTD 这样的复杂出生缺陷可能是全基因的，涉及相互关联的基因调控网络，以及整个基因组中的相关信号。技术的进步使研究人员能够以越来越详细的方式更严格地研究调控基因网络，让我们了解 NTD 的遗传基础。使用大规模并行 DNA 测序和严格的生物信息学算法对这些复杂的出生缺陷进行系统分析，可以更深入地了解 NTD 的基因组结构。在此，我们简要概述了我们实验室为剖析 NTD 易感性遗传学而采取的不同方法。这涉及使用小鼠模型来识别候选基因，以及大规模的全基因组/全外显子组 (WGS/WES) 研究来询问 NTD 的基因组景观。