Dataset Information

Assessment of candidate genes and genetic heterogeneity in human non syndromic orofacial clefts specifically non syndromic cleft lip with or without palate.

ABSTRACT: Non syndromic orofacial clefts specifically non-syndromic cleft lip/palate are one of the most common craniofacial malformation among birth defects in human having multifactorial etiology with an incidence of 1:700/1000. On the basis of association with other congenital malformations or their presence as isolated anomaly, OFC can be classified as syndromic (30%) and nonsyndromic (70%) respectively. The major cause of disease demonstrates complex interplay between genetic and environmental factors. The pathogenic mechanism of underlying factors have been provided by different genetic studies on large-scale with significant recent advances in genotyping technologies usually based on linkage or genome wide association studies (GWAS). On the basis of recent studies, new tools to identify causative genes involved in NSCL/P reported approximately more than 30 genetic risk loci that are responsible for pathogenesis of facial deformation. Despite these findings, it is still uncertain that how much of variance in NSCL/P predisposing factors can be explain by identified risk loci, as they all together accounts for only 20%-25% of NSCL/P heritability. So there is need of further findings about the problem of rare low frequency coding variants and other missing responsive factors or genetic modifiers. This review will described those potential genes and loci reported in different studies whose involvement in pathogenesis of nonsyndromic OFC has wide scientific evidence.

SUBMITTER: Saleem K

PROVIDER: S-EPMC6921104 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Assessment of candidate genes and genetic heterogeneity in human non syndromic orofacial clefts specifically non syndromic cleft lip with or without palate.

Saleem Komal K Zaib Tahir T Sun Wenjing W Fu Songbin S

Heliyon 20191213 12

Non syndromic orofacial clefts specifically non-syndromic cleft lip/palate are one of the most common craniofacial malformation among birth defects in human having multifactorial etiology with an incidence of 1:700/1000. On the basis of association with other congenital malformations or their presence as isolated anomaly, OFC can be classified as syndromic (30%) and nonsyndromic (70%) respectively. The major cause of disease demonstrates complex interplay between genetic and environmental factor ...[more]

PMID: 31886431

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Project description:The etiology and pathogenesis of non-syndromic cleft lip and palate (NSCL/P) are largely unknown. Long non-coding RNAs (lncRNA) are thought to play important roles in NSCL/P, but reports on the underlying processes are currently unavailable. Our study focused on children diagnosed with NSCL/P alone. Based on the morphology, patients were categorized as either cleft lip with or without cleft palate (CL/P) or cleft palate-only (CPO). When patients received surgery for NSCL/P, tissue excised from the trimmed wound edge was reserved to serve as experimental samples; adjacent normal tissue was used as a positive control. Target lncRNAs in the collected tissues were identified using microarray and quantitative reverse transcription PCR (RT-qPCR). Immunohistochemical (IHC) staining and RT-qPCR were used to verify the target mRNAs. Pathway, gene ontology (GO) enrichment, and TargetScan prediction were employed to construct endogenous RNA networks (ceRNA networks) and explore their potential functions. RNA-Seq analysis revealed 24 upregulated and 43 downregulated lncRNAs in the CL/P and CPO groups compared with those in the control group; of these, MALAT1and NEAT1 were screened and validated using RT-qPCR. Common NSCL/P risk factors positively correlated with MALAT1 and NEAT1 expression (ORMALAT1 = 28.111, 95% CI: 4.054-194.923; ORNEAT1 = 30.556, 95% CI: 4.422-211.142; P < 0.05). Bioinformatics predicted four ceRNA networks: MALAT1-hsa-miR-1224-3p-SP1, MALAT1-hsa-miR-6734-5p/hsa-miR-1224-3p-WNT10A, NEAT1-hsa-miR-140-3p.1-CXCR4, and NEAT1-hsa-miR-3129-5p/hsa-miR-199a-3p/hsa-miR-199b-3p-ZEB1. GO enrichment focused on the potential functions of ceRNA networks, including biosynthesis of organic cyclic compounds, formation of membrane-enclosed and organelle lumens, and Wnt-protein binding. The results of RT-qPCR were consistent with those of IHC staining with regard to expression of related mRNAs. MALAT1 and NEAT1, which are upregulated in NSCL/P, are associated with the severity of NSCL/P. This study provides a new insight into NSCL/P pathogenesis and suggests that MALAT1 and NEAT1 act as potential therapeutic targets and prognostic biomarkers for NSCL/P.

Dataset Information

Assessment of candidate genes and genetic heterogeneity in human non syndromic orofacial clefts specifically non syndromic cleft lip with or without palate.

Publications

Assessment of candidate genes and genetic heterogeneity in human non syndromic orofacial clefts specifically non syndromic cleft lip with or without palate.

Similar Datasets

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