Association Between a 45-bp 3′Untranslated Insertion/Deletion Polymorphism in Exon 8 of UCP2 Gene and Neural Tube Defects in a High-Risk Area of China

Wang, Jingyuan; Chi, Liu; Zhao, Hengyu; Wang, Fang; Guo, Jin; Xie, Hua; Lü, Xiaolin; Bao, Yihua; Pei, Lijun; Niu, Bo; Zhong, Rugang; Zheng, Xiaoying; Zhang, Ting

doi:10.1177/1933719110393026

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…Previous studies supported that low folate levels, and polymorphism of folate-metabolic genes were risk factors for NTDs in this region [58], [59], [60]. Genes regulating early embryonic development were also identified as risk factors of NTDs in this region [61], [62], [63]. The significant involvement of copy number variants in NTD revealed by this study further suggests the complex genetic heterogeneity underlying NTD pathogenesis in the Shanxi region.…”

Section: Discussionsupporting

confidence: 77%

Detection of Copy Number Variants Reveals Association of Cilia Genes with Neural Tube Defects

et al. 2013

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BackgroundNeural tube defects (NTDs) are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs) detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs.MethodsThe genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants) CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined.ResultsFifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV). Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05). Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24–5.87). Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05), corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27–8.01). Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways.ConclusionsEvidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis.

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Section: Discussionsupporting

confidence: 77%

Detection of Copy Number Variants Reveals Association of Cilia Genes with Neural Tube Defects

et al. 2013

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“…This was consistent with previous studies. 9,35,36 But as the sample limits, comparing between different educational level did not get significant result and the association results specific to each educational level were the same direction as total samples.…”

Section: Discussionmentioning

confidence: 86%

Association Study of PARD3 Gene Polymorphisms With Neural Tube Defects in a Chinese Han Population

et al. 2012

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Partitioning defective 3 homolog (PARD3) is an attractive candidate gene for screening neural tube defect (NTD) risk. To investigate the role of genetic variants in PARD3 on NTD risk, a case-control study was performed in a region of China with a high prevalence of NTDs. Total 53 single-nucleotide polymorphisms (SNPs) in PARD3 were genotyped in 224 fetuses with NTDs and in 253 normal fetuses. We found that 6 SNPs (rs2496720, rs2252655, rs3851068, rs118153230, rs10827337, and rs12218196) were statistically associated with NTDs (P < .05). After stratifying participants by NTD phenotypes, the significant association only existed in cases with anencephaly rather than spina bifida. Further haplotype analysis confirmed the association between PARD3 polymorphisms and NTD risk (global test P = 3.41e-008). Our results suggested that genetic variants in PARD3 were associated with susceptibility to NTDs in a Chinese Han population, and this association was affected by NTD phenotypes.

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“…Undifferentiated hPSCs generate few fragmented, punctate mitochondria (lacking cristae) by undergoing fission and meet their energy needs via anaerobic pathways, while differentiated cells generate an extensive branched mitochondrial network . REX1‐depleted hESCs, which lose pluripotency, show a dramatic shift from exhibiting small and fragmented mitochondria with poorly developed cristae (an immature mitochondrial structure) to displaying elongated, cristae‐rich mitochondria (a mature mitochondrial structure).…”

Section: Discussionmentioning

confidence: 99%

Unveiling the critical role of REX1 in the regulation of human stem cell pluripotency

et al. 2013

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Reduced expression 1 (REX1) is a widely used pluripotency marker, but little is known about its roles in pluripotency. Here, we show that REX1 is functionally important in the reacquisition and maintenance of pluripotency. REX1-depleted human pluripotent stem cells (hPSCs) lose their self-renewal capacity and full differentiation potential, especially their mesoderm lineage potential. Cyclin B1/B2 expression was found to parallel that of REX1. REX1 positively regulates the transcriptional activity of cyclin B1/B2 through binding to their promoters. REX1 induces the phosphorylation of DRP1 at Ser616 by cyclin B/CDK1, which leads to mitochondrial fission and appears to be important for meeting the high-energy demands of highly glycolytic hPSCs. During reprogramming to pluripotency by defined factors (OCT4, SOX2, KLF4, and c-MYC), the reprogramming kinetics and efficiency are markedly improved by adding REX1 or replacing KLF4 with REX1. These improvements are achieved by lowering reprogramming barriers (growth arrest and apoptosis), by enhancing mitochondrial fission, and by conversion to glycolytic metabolism, dependent on the cyclin B1/B2-DRP1 pathway. Our results show that a novel pluripotency regulator, REX1, is essential for pluripotency and reprogramming.

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Association Between a 45-bp 3′Untranslated Insertion/Deletion Polymorphism in Exon 8 of UCP2 Gene and Neural Tube Defects in a High-Risk Area of China

Cited by 9 publications

References 35 publications

Detection of Copy Number Variants Reveals Association of Cilia Genes with Neural Tube Defects

Detection of Copy Number Variants Reveals Association of Cilia Genes with Neural Tube Defects

Association Study of PARD3 Gene Polymorphisms With Neural Tube Defects in a Chinese Han Population

Unveiling the critical role of REX1 in the regulation of human stem cell pluripotency

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