Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA182323 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:this study analyzes the WGBS of twins discordant for non syndromic cleft lip and palate
2021-04-24 | GSE173211 | GEO
Project description:Genome-wide DNA methylation profilinf from 67 non syndromic cleft lip and palate samples and controls using whole-blood DNA and Illumina Infinium Human Methylation 450K Bead array, in which over 485000 CpGs sites were analysed per sample
2018-01-31 | GSE93933 | GEO
Project description:A 640kb non-coding interval at 8q24 has been associated with an increased risk of non-syndromic cleft lip and palate (CLP) in humans, but the genes and pathways involved in this genetic susceptibility have remained elusive. With a large series of rearrangements engineered over the syntenic mouse region, we showed that this interval contains very remote cis-acting enhancers that control c-myc expression in the developing face. Deletion of this interval led to mild alteration of facial morphologies in mice and, sporadically, to CLP. At a molecular level, we identified mis-expression of several downstream genes, highlighting a combined impact on cranio-facial developmental network and general metabolic capacity. This dual molecular etiology may account for the prominent role to the 8q24 region in human facial dysmorphologies. ChIP-seq and transcriptomics analysis in wt or/and mutant mice
2014-04-03 | E-GEOD-52974 | biostudies-arrayexpress
Project description:A 640kb non-coding interval at 8q24 has been associated with an increased risk of non-syndromic cleft lip and palate (CLP) in humans, but the genes and pathways involved in this genetic susceptibility have remained elusive. With a large series of rearrangements engineered over the syntenic mouse region, we showed that this interval contains very remote cis-acting enhancers that control c-myc expression in the developing face. Deletion of this interval led to mild alteration of facial morphologies in mice and, sporadically, to CLP. At a molecular level, we identified mis-expression of several downstream genes, highlighting a combined impact on cranio-facial developmental network and general metabolic capacity. This dual molecular etiology may account for the prominent role to the 8q24 region in human facial dysmorphologies.
2014-04-03 | GSE52974 | GEO
Project description:Long Non-Coding RNAs MALAT1 and NEAT1 in Non-syndromic Cleft Lip and Palate
| PRJNA761123 | ENA
Project description:Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88x10-2 – 5.02x10-9). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 involved in DNA repair are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show that cellular defences against DNA damage may take part in the pathogenesis of NSCL/P, in accordance with the hypothesis of aetiological overlap between this malformation and cancer. These results provide more information regarding the aetiology of NSCL/P and have the potential tocan potentially assist incontribute to the development of future preventive strategies.
2014-01-01 | GSE42589 | GEO
Project description:Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88x10-2 M-bM-^@M-^S 5.02x10-9). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 involved in DNA repair are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show that cellular defences against DNA damage may take part in the pathogenesis of NSCL/P, in accordance with the hypothesis of aetiological overlap between this malformation and cancer. These results provide more information regarding the aetiology of NSCL/P and have the potential tocan potentially assist incontribute to the development of future preventive strategies. In order to analyze differences in gene expression between NSCL/P samples and controls we used 7 NSCL/P RNA samples extracted from dental pulp stem cells cultures and 6 control RNA samples also from dental pulp stem cells cultures, all in the same culture conditions. RNA samples were used in gene expression microarrays (Affymetrix HuGene 1.0 st chips).
2014-01-01 | E-GEOD-42589 | biostudies-arrayexpress
Project description:Exome sequencing in non syndromic cleft palate
| PRJEB44884 | ENA
Project description:Cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex, heterogeneous etiology. It is well-established that both common and rare sequence variants contribute to the formation of CL/P, however, the contribution of copy number variants (CNVs) to cleft formation remains relatively understudied. To fill this knowledge gap, we conducted a large-scale comparative analysis of genome-wide CNV profiles of 869 individuals from the Philippines and 233 individuals of European ancestry with CL/P with three primary goals: first, to evaluate whether differences in CNV number, amount of genomic content, or amount of coding genomic content existed within clefting subtypes; second, to assess whether CNVs in our cohort overlapped with known Mendelian clefting loci; and third, to identify unestablished Mendelian clefting genes. Significant differences in CNVs across cleft types or in individuals with non-syndromic versus syndromic clefts were not observed, however, several CNVs in our cohort overlapped with known syndromic and non-syndromic Mendelian clefting loci. Moreover, employing a filtering strategy relying on population genetics data that rare variants are on the whole more deleterious than common variants, we identify several CNV-associated gene losses likely driving non-syndromic clefting phenotypes. By prioritizing genes deleted at a rare frequency across multiple individuals with clefts yet enriched in our case cohort compared to controls, we identify COBLL1, RIC1, and ARHGEF38 as clefting genes. CRISPR/Cas9 mutagenesis of these genes in Xenopus laevis and Danio rerio yielded craniofacial dysmorphologies, including clefts analogous to those seen in human clefting disorders.
2022-12-01 | GSE212166 | GEO