Dataset Information

Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology.

ABSTRACT: Non-syndromic cleft lip with or without palate (NSCL/P) is a frequent malformation of the facial region. Genetic variants (SNPs) within nineteen loci have been previously associated with NSCL/P in GWAS studies of European individuals. These common variant SNPs may have subtler effects on the morphology of the lip and face in unaffected individuals. Several studies have investigated the genetic influences on facial morphology using land-marking methods, but these landmarks are sparse in the lip region. The aim of this study is to assess for associations between the nineteen NSCL/P SNPs and normal lip phenotypes, using a detailed categorical scale. Three-dimensional laser scanned facial images were obtained of 4,747 subjects recruited from the Avon Longitudinal Study of Parents and Children (ALSPAC) and genetic data was available for 3,643 of them. A polygenetic risk score (PRS) combining the nineteen NSCL/P SNPs was associated with V-shaped Cupid's bow (P = 3 × 10-4) and narrow philtrum (P = 2 × 10-4) phenotypes. Analysis of individual SNPs found strong evidence for association between rs227731 and skeletal II pattern (P = 5 × 10-6). This study finds that known NSCL/P SNPs affect lip phenotypes in the general population, and an increased PRS is associated with narrow philtrum and V-shaped Cupid's bow. However, the difference in NSCL/P PRS between people with and without certain lip features is unlikely to be great enough to serve as a useful marker of NSCL/P risk.

SUBMITTER: Wilson-Nagrani C

PROVIDER: S-EPMC6207999 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology.

Wilson-Nagrani Caryl C Richmond Stephen S Paternoster Lavinia L

Frontiers in genetics 20181024

Non-syndromic cleft lip with or without palate (NSCL/P) is a frequent malformation of the facial region. Genetic variants (SNPs) within nineteen loci have been previously associated with NSCL/P in GWAS studies of European individuals. These common variant SNPs may have subtler effects on the morphology of the lip and face in unaffected individuals. Several studies have investigated the genetic influences on facial morphology using land-marking methods, but these landmarks are sparse in the lip r ...[more]

PMID: 30405682

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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

Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology.

Publications

Non-syndromic Cleft Lip and Palate Polymorphisms Affect Normal Lip Morphology.

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