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Pedigree of the Mexican family with recurrence of gastroschisis. Square and circle symbols depict males and females, respectively. Solid symbols indicate gastroschisis cases (III‐1 and III‐2), semisolid symbols indicate cases of umbilical hernia (I‐2 and I‐3), and the open symbols indicate unaffected individuals. The arrow points to the proband
Source publication
Background:
Genetic association studies for gastroschisis have highlighted several candidate variants. However, genetic basis in gastroschisis from noninvestigated heritable factors could provide new insights into the human biology for this birth defect. We aim to identify novel gastroschisis susceptibility variants by employing whole exome sequen...
Citations
... 36 miR-143 is related to several processes linked to the pathophysiology of GS by regulating smooth muscle contraction, intestinal angiogenesis, and cellular response to DNA damage. 37 Overexpression of miR-143 leads to increased intestinal inflammation, 38 such as the genes of the Mitogen-Activated Protein Kinase (MAPK) family, 39 Intercellular Adhesion Molecule 1 (I-CAM 1) and Nitric Oxide Synthase 3 (NOS 3), 40 and TGF-β3 which is more involved in intestinal motility dysfunction. 10 The present results demonstrate a higher expression of miR-143 in GS 18 compared to the control group and GS 19. ...
Objective
Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs.
Methods
Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR).
Results
BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05).
Conclusions
The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.
... Thuy Duong Nguyen 1, 2* , Thi Khanh Ly Nguyen 1 , Thi Thu Ha Duong 1 1 june 2022 • Volume 64 number 2 as a new gene candidate for fertility impairment due to its functions regarding sperm flagellar morphology and paraflagellar rod synthesis [12,13]. ...
... The CFAP65 encodes cilia-and flagella-associated protein 65, which is highly expressed in testis during spermatogenesis. Several mutations on CFAP65 have been reported to cause male infertility [8,12,14]. Consequently, the association between single nucleotide polymorphisms on this gene and the risk of male fertility is expected to be a good consideration. The polymorphism of rs56411706 occurring in the coding region of the CFAP65 gene was analysed in silico using SIFT. ...
Approximately two thousand genes have been found to be involved in spermatogenesis and their mutations have been reportedly associated with male infertility. Recent studies have shown that CFAP65 was crucial for spermatogenesis, and several mutations in this gene could result in male infertility. However, the association of polymorphisms in CFAP65 with male infertility remains unknown. In this study, the relationship between CFAP65 rs56411706 and male infertility was assessed in a Vietnamese population by 171 male infertility patients who had been diagnosed with non-obstructive azoospermia (NOA), oligozoospermia, or asthenozoospermia while 222 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analysis demonstrated that the allele frequencies of CFAP65 rs56411706 followed Hardy-Weinberg equilibrium (HWE) (p>0.05). The Chi-square test revealed no correlation between the polymorphism and male infertility in this study (p>0.05). This is the first study on the association between a single nucleotide polymorphism in the CFAP65 gene and male infertility in a Vietnamese population. The results of this study would help enrich the knowledge about the effects of CFAP65 polymorphisms on male infertility in the Vietnamese population.
... In Case 1 the predominant hypomethylation profile was associated with a neuronal component (recurrence case). Another study with a different approach used exome sequencing in two gastroschisis sisters and found inherited changes located in genes linked to the blood vessel, circulatory system, muscular structure, epithelium and epidermis, regulation of the cellular junction, biological/cellular adhesion, detection/response to endogenous stimuli, and regulation of biosynthetic cytokine (Salinas-Torres et al., 2020). However, the lack of related studies with our case hindered the correlation of findings. ...
Background:
To reveal the complex etiology of gastroschisis through two independent cases.
Cases:
Case 1 involves gastroschisis recurrence in a consanguineous marriage, and Case 2 concerns a fetus with gastroschisis whose mother had undergone gastroplasty. Methylation array was carried out in both cases (two fetuses with gastroschisis, their two mothers, one father from the consanguineous marriage), and in 16 controls (fetuses and their respective mothers).
Conclusion:
The two cases presented different noninherited methylation profiles.
... It binds to ubiquitin-conjugating enzyme E2V2 [55][56][57] and interacts with E3 ubiquitin ligase in the polyubiquitination reaction and cell cycle progression [58]. UBE2NL has been found to be a novel type 2 diabetes relevant gene [59] and a novel candidate gene in familial gastroschisis [60]. It also expresses in the brain and participates in parkin-mediated mitophagy as a genetic risk factor for sporadic Alzheimer's disease [54]. ...
Background:
Clinical studies have shown that electroacupuncture (EA) promotes gallbladder motility and alleviates gallstone. However, the mechanism underlying the effects of EA on gallstone is poorly understood. In this study, the mRNA transcriptome analysis was used to study the possible therapeutic targets of EA.
Methods:
Hartley SPF guinea pigs were employed for the gallstone models. Illumina NovaSeq 6000 platform was used for the RNA sequencing of guinea pig gallbladders in the normal group (Normal), gallstone model group (Model), and EA-treated group (EA). Differently expressed genes (DEGs) were examined separately in Model vs. Normal and EA vs. Model. DEGs reversed by EA were selected by comparing the DEGs of Model vs. Normal and EA vs. Model. Biological functions were enriched by gene ontology (GO) analysis. The protein-protein interaction (PPI) network was analyzed.
Results:
After 2 weeks of EA, 257 DEGs in Model vs. Normal and 1704 DEGs in EA vs. Model were identified. 94 DEGs reversed by EA were identified among these DEGs, including 28 reversed upregulated DEGs and 66 reversed downregulated DEGs. By PPI network analysis, 10 hub genes were found by Cytohubba plugin of Cytoscape. Quantitative real-time PCR (qRT-PCR) verified the changes.
Conclusion:
We identified a few GOs and genes that might play key roles in the treatment of gallstone. This study may help understand the therapeutic mechanism of EA for gallstone.
... 10,11 However, genetic studies are still controversial and have been unable to provide enough data on the etiopathology of gastroschisis (Table 1). [11][12][13][14][15][16][17][18][19][20][21][22] Different molecular methods of investigation were used (sequencing, polymerase chain reaction with restriction fragment length polymorphism, panel, array comparative genomic hybridization, shared genomic segment, and whole exome sequencing) and different genes were related. These findings, however, have not been replicated, preventing confirmation of the involvement of such genes in gastroschisis. ...
... These findings, however, have not been replicated, preventing confirmation of the involvement of such genes in gastroschisis. [12][13][14][15][16][17][18][19][20][21][22] Recent studies have shown that, when deregulated, deoxyribonucleic acid (DNA) methylation may be associated with several diseases such as cancer, type 2 diabetes, neurological disorders, obesity, and autoimmune diseases. [23][24][25][26][27] To the best of our knowledge, the gastroschisis methylation profile has not been researched to date. ...
Abstract
Objective: The purpose of this study was to describe the genomic DNA methylation profile in fetuses with gastroschisis, determine whether the profile was inherited, and investigate any possible correlations with maternal risk factors.
Methods: Genome-wide DNA methylation analysis of 96 blood samples was performed using the Illumina Human Methylation 850K BeadChip. The blood samples were collected as follows: 32 from the umbilical cord of fetuses with gastroschisis, 32 from their respective mothers, 16 from the umbilical cord of fetuses without malformation, and 16 from their respective mothers.
Results: The differential DNA methylation analysis showed a significant difference between the groups. The enrichment analysis resulted in 12 sites related to T-cell activation (p = 0.0128). The sites with different methylation status contained 10 genes, 3 of which were related to the B2M gene. The methylation profile observed in the fetuses with gastroschisis was not inherited from the mothers. In addition, there was no association between maternal urinary tract infection, smoking, and alcohol use and different methylated sites.
Conclusion: We established the methylation profile of gastroschisis fetuses, which differs from that of normal fetuses. The profile was not inherited and did not correlate with maternal risk factors. This article is protected by copyright. All rights reserved.
Keywords: B2M gene; T-cell activation; fetal gastroschisis; methylation array.
... Cardiac anomalies such as truncus arteriosus and interrupted aortic arch are known to be associated with 22q11 deletion syndrome while others such as hypoplastic left heart syndrome are less often associated with a genetic syndrome (Li et al. 2017). Open neural tube defects and midline abdominal defects such as gastroschisis observed in isolation have also been low-yield in genomic sequencing studies (Ross et al. 2017, Salinas-Torres et al. 2020). Future research is likely to reveal genomic changes causing such apparently isolated anomalies. ...
Congenital anomalies, or structural birth defects, are common in the population, with 2-3% of infants estimated to have at least one major congenital malformation and countless others with minor malformations of lesser cosmetic or medical importance. As congenital malformations are major drivers of morbidity and mortality, representing the leading cause of infant mortality in the United States, there is substantial interest in understanding the underlying etiologies - particularly if modifiable causes may be identified or pre- or postnatal treatments can be offered. Recent research has begun to elucidate the spectrum of monogenic Mendelian disorders that commonly result in birth defects, and newer techniques and approaches have revealed non-Mendelian genetic contributions as well. Environmental effects, including teratogenic exposures, continue to also be important contributors. Future research will aid in further understanding the genetic, genomic, and environmental interactions that result in congenital anomalies and ideally will lead to targeted therapies.
Fibroblast Growth Factor Receptor Like 1 (FGFRL1) signalling has crucial role in a multitude of processes during genetic diseases, embryonic development and various types of cancer. Due to its partial structural similarity with its classical Fibroblast Growth Factor Receptor [FGFR] counterparts and lack of tyrosine kinase domain, FGFRL1 was thought to work as a decoy receptor in FGF/FGFR signalling. Later on, growing number evidences showed that expression of FGFRL1 affects major pathways like ERK1/2, Akt and others, which are dysfunctional in a wide range of human cancers. In this review, we provide an overview of the current understanding of FGFRL1 and its roles in cell differentiation, adhesion and proliferation pathways . Overexpression of FGFRL1 might lead to tumor progression and invasion. In this context, inhibitors for FGFRL1 might have therapeutic benefits in human cancer prognosis.
Neuroblastoma (NB) has the highest incidence of all extracranial solid tumors in children and is highly lethal. This study aims to establish a prognostic model of NB with MYCN-related genes. We determined the gene expression profiles of 900 NB samples from the UCSC database and four Gene Expression Omnibus (GEO) data sets, and performed a comprehensive bioinformatics analysis and clinical sample verification. After univariate Cox regression, least absolute shrinkage and selection operator (Lasso), and multivariate Cox regression analyses, four (AKR1C1, CHD5, PDE4DIP, and PRKACB) genes were finally selected and used to construct a risk score prognostic model. In the UCSC data set, the high-risk group exhibited a significantly worse prognosis than the low-risk group. In addition, the nomogram, which includes prognostic markers and clinical factors, demonstrates high prognostic value. Finally, the differential expression of the four genes in the model was verified by quantitative real-time PCR in clinical tissues. These findings of MYCN-related genes provide a new and reliable prognostic model for NB related to MYCN.
