Transcription factors dysregulated in three complex birth defects datasets
Transcription factors dysregulated in three complex birth defects datasets
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DOI：
10.1097/rd9.0000000000000018
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发表时间：
2022-06-01
影响因子：
0.8
通讯作者：
Lei, Yun-Ping
中科院分区：
文献类型：
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作者：
Chen, Zhong-Zhong;Gao, Yun-Qian;Lei, Yun-Ping
目的：探讨转录因子（TF）在复杂人类出生缺陷病因学中的作用，包括神经管缺陷（NTD）、先天性心脏病（CHD）和尿道下裂。方法：我们检查了 NTD、CHD 和尿道下裂之间遗传相关基因的重叠。然后，我们根据所有检测到的基因和与疾病相关的 TF 比较了这些疾病的表达谱。我们获得的差异表达转录因子进一步进行功能富集分析，以阐明它们在这些出生缺陷的发展中的作用。结果：复杂出生缺陷中TF基因显着富集(P = 5.95 x 10(-24))。与对照组相比，NTD、CHD 和尿道下裂显示出不同的基因表达谱。尽管 TF 不能有效地将 CHD 与正常受试者区分开，但 TF 不同的基因表达谱可以将 NTD 和尿道下裂与对照区分开来。差异表达的 TF 可用于表征 NTD、尿道下裂和对照。生物过程（BP）中丰富的TF反映了NTD、CHD和尿道下裂的不同形态过程。结论：本研究表明，特定 TF 的异常表达模式可能会通过相关 BP 破坏发育平衡的正常要求。对三种不同复杂出生缺陷的遗传相关基因和基因表达谱的研究为 TF 失调如何影响其发育过程提供了新的见解。
Objective: To investigate the roles of transcription factors (TFs) in the etiology of complex human birth defects, including neural tube defects (NTDs), congenital heart diseases (CHDs), and hypospadias. Methods: We examined the overlap of genetically associated genes among NTDs, CHDs, and hypospadias. We then compared the expression profiles of these diseases based on all the detected genes and disease-associated TFs. The differentially expressed TFs that we obtained were further subjected to functional enrichment analysis to elucidate their role in the development of these birth defects. Results: TF genes were significantly enriched in complex birth defects (P = 5.95 x 10(-24)). NTDs, CHDs, and hypospadias showed distinct gene expression profiles compared with the controls. Although TFs could not efficiently separate CHDs from normal subjects, distinct gene expression profiles of TFs could distinguish NTDs and hypospadias from controls. Differentially expressed TFs can be used to characterize NTDs, hypospadias, and controls. The enriched TFs in biological processes (BPs) reflected the different morphological processes of NTDs, CHDs, and hypospadias. Conclusions: This study indicates that abnormal expression patterns of specific TFs may disrupt the normal requirements for developmental equilibrium through the related BPs. The investigation of genetically associated genes and gene expression profiles for the three different complex birth defects provides new insights into how the dysregulation of TFs influences their developmental process.