Knockdown of Crispld2 in zebrafish identifies a novel network for nonsyndromic cleft lip with or without cleft palate candidate genes
| Autor: | Ariadne Letra, Jacqueline T. Hecht, Matthew R. Greives, Ryan A. Boyer, John F. Teichgraeber, Jeffrey Dyke, John B. Mulliken, Qiuping Yuan, Eric C. Swindell, Susan H. Blanton, Lorena Maili, Robert Plant, Brett T. Chiquet |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Candidate gene Genotype Cleft Lip In silico Gene regulatory network 030105 genetics & heredity Polymorphism Single Nucleotide Article 03 medical and health sciences Genetics Animals Humans Genetic Predisposition to Disease Zebrafish Gene Genetics (clinical) Glycoproteins Gene knockdown biology Haplotype Gene Expression Regulation Developmental Epistasis Genetic Zebrafish Proteins biology.organism_classification Cleft Palate 030104 developmental biology Haplotypes Gene Knockdown Techniques Neural crest cell migration |
| Zdroj: | European Journal of Human Genetics. 26:1441-1450 |
| ISSN: | 1476-5438 1018-4813 |
| Popis: | Orofacial development is a multifaceted process involving tightly regulated genetic signaling networks, that when perturbed, lead to orofacial abnormalities including cleft lip and/or cleft palate. We and others have shown an association between the cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2) gene and nonsyndromic cleft lip with or without cleft palate (NSCLP). Further, we demonstrated that knockdown of Crispld2 in zebrafish alters neural crest cell migration patterns resulting in abnormal jaw and palate development. In this study, we performed RNA profiling in zebrafish embryos and identified 249 differentially expressed genes following knockdown of Crispld2. In silico pathway analysis identified a network of seven genes previously implicated in orofacial development for which differential expression was validated in three of the seven genes (CASP8, FOS, and MMP2). Single nucleotide variant (SNV) genotyping of these three genes revealed significant associations between NSCLP and FOS/rs1046117 (GRCh38 chr14:g.75746690 T > C, p = 0.0005) in our nonHispanic white (NHW) families and MMP2/rs243836 (GRCh38 chr16:g.55534236 G > A; p = 0.002) in our Hispanic families. Nominal association was found between NSCLP and CASP8/rs3769825 (GRCh38 chr2:g.202111380 C > A; p |
| Databáze: | OpenAIRE |
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