Homo sapiens
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PROVIDER: PRJNA294630 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptomic Profiling of Posterior Polymorphous Corneal Dystrophy
| PRJNA354865 | ENA
Project description:To investigate the molecular basis of posterior polymorphous corneal dystrophy (PPCD) by examining the transcriptome in affected individuals and the effect of decreased ZEB1 expression on corneal endothelial gene expression.
2017-08-17 | GSE90489 | GEO
Project description:To investigate the molecular basis of posterior polymorphous corneal dystrophy (PPCD) by examining the transcriptome in an affected individuals with an OVOL2 promoter mutation c.307T>C (PPCD1).
2019-04-11 | GSE126487 | GEO
Project description:Purpose: To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) in families mapped to the PPCD1 locus and in affected individuals without ZEB1 coding region mutations. Methods: The promoter and/or coding regions of OVOL2 were screened in the PPCD family in which linkage analysis established the PPCD1 locus and in 26 PPCD probands who did not harbor a ZEB1 mutation. Copy number variation (CNV) analysis in the PPCD1 and PPCD3 intervals was performed on DNA samples from eight probands using aCGH. Luciferase reporter assays were performed in human corneal endothelial cells to determine the impact of the identified potentially pathogenic variants on OVOL2 promoter activity. Results: OVOL2 screening in the first PPCD1-linked family demonstrated segregation of the c.-307T>C variant with the affected phenotype. In the other 26 probands screened, one heterozygous coding region variant and five promoter region heterozygous variants were identified, though none are likely pathogenic based on allele frequency. Array CGH in the PPCD1 and PPCD3 loci excluded the presence of CNV involving either OVOL2 or ZEB1, respectively. The c.-307T>C variant demonstrated increased promoter activity when compared to the wild-type sequence. Conclusions: The previously identified and presumed pathogenic OVOL2 promoter variant c.-307T>C was identified in the PPCD family that established the PPCD1 locus. However, the failure to identify presumed pathogenic coding or non-coding OVOL2 or ZEB1 variants, or CNV involving the PPCD1 and PPCD3 loci in 26 other PPCD probands suggests that other genetic loci may be involved in the pathogenesis of PPCD.
2017-03-08 | GSE84940 | GEO
Project description:Purpose: To identify the genetic basis of posterior polymorphous corneal dystrophy 1 (PPCD1). Methods: Next-generation sequencing was performed on DNA samples from 4 affected and 4 unaffected members of a previously reported family with PPCD1 linked to chromosome 20 between D20S182 and D20S195. Custom capture probes were utilized for targeted region capture of the linked interval. Single nucleotide variants (SNVs) and insertions/deletions (indels) were identified using two bioinformatics pipelines and two annotation databases. Candidate variants met the following criteria: quality score â¥20, read depth â¥5X, heterozygous, novel or rare (minor allele frequency (MAF) ⤠0.05), present in each affected individual and absent in each unaffected individual. Structural variants were detected with two different microarray platforms to identify indels of varying sizes. Results: Sequencing reads aligned to the linked region on chromosome 20, and high coverage was obtained across the sequenced region. The majority of identified variants were detected with both pipelines and annotation databases, although unique variants were identified. Twelve SNVs in 10 genes (2 synonymous variants and 10 noncoding variants) and 9 indels in 7 genes met the filtering criteria and were considered candidate variants for PPCD1. Conclusions: Next-generation sequencing of the PPCD1 interval has identified 17 genes containing novel or rare SNVs and indels that segregate with the affected phenotype in an affected family previously mapped to the PPCD1 locus. We anticipate that screening of these candidate genes in other families previously mapped to the PPCD1 locus will result in the identification of the genetic basis of PPCD1. Four affected and 4 unaffected individuals from a single family were analyzed for copy number variation within the PPCD1 disease locus. Array design and analysis is based on genome build hg19.
2016-06-30 | E-GEOD-72617 | biostudies-arrayexpress
Project description:Purpose: To identify the genetic basis of posterior polymorphous corneal dystrophy 1 (PPCD1). Methods: Next-generation sequencing was performed on DNA samples from 4 affected and 4 unaffected members of a previously reported family with PPCD1 linked to chromosome 20 between D20S182 and D20S195. Custom capture probes were utilized for targeted region capture of the linked interval. Single nucleotide variants (SNVs) and insertions/deletions (indels) were identified using two bioinformatics pipelines and two annotation databases. Candidate variants met the following criteria: quality score ≥20, read depth ≥5X, heterozygous, novel or rare (minor allele frequency (MAF) ≤ 0.05), present in each affected individual and absent in each unaffected individual. Structural variants were detected with two different microarray platforms to identify indels of varying sizes. Results: Sequencing reads aligned to the linked region on chromosome 20, and high coverage was obtained across the sequenced region. The majority of identified variants were detected with both pipelines and annotation databases, although unique variants were identified. Twelve SNVs in 10 genes (2 synonymous variants and 10 noncoding variants) and 9 indels in 7 genes met the filtering criteria and were considered candidate variants for PPCD1. Conclusions: Next-generation sequencing of the PPCD1 interval has identified 17 genes containing novel or rare SNVs and indels that segregate with the affected phenotype in an affected family previously mapped to the PPCD1 locus. We anticipate that screening of these candidate genes in other families previously mapped to the PPCD1 locus will result in the identification of the genetic basis of PPCD1.
2016-06-30 | GSE72617 | GEO
Project description:Confirmation of the OVOL2 Promoter Mutation c.-307T>C in Posterior Polymorphous Corneal Dystrophy 1
| PRJNA335716 | ENA
Project description:Posterior amorphous corneal dystrophy (PACD) is a rare, autosomal dominant disorder affecting the cornea and iris. After next-generation sequencing of the family in which linkage analysis identified a chromosomal locus for PACD on 12q21.33 failed to yield a pathogenic mutation, array-based copy number analysis and qPCR detected a deletion on 12q21.33 containing four genes encoding small leucine-rich proteoglycans (SLRPs): KERA, LUM, DCN, and EPYC. Two other families with PACD also demonstrated deletion of these SLRPs, which together with murine models of KERA, LUM, and DCN deficiency provide convincing evidence that PACD is caused by haploinsufficiency of these SLRPs.
2014-06-04 | GSE50573 | GEO
Project description:Posterior amorphous corneal dystrophy (PACD) is a rare, autosomal dominant disorder affecting the cornea and iris. After next-generation sequencing of the family in which linkage analysis identified a chromosomal locus for PACD on 12q21.33 failed to yield a pathogenic mutation, array-based copy number analysis and qPCR detected a deletion on 12q21.33 containing four genes encoding small leucine-rich proteoglycans (SLRPs): KERA, LUM, DCN, and EPYC. Two other families with PACD also demonstrated deletion of these SLRPs, which together with murine models of KERA, LUM, and DCN deficiency provide convincing evidence that PACD is caused by haploinsufficiency of these SLRPs. Copy number analysis of 750K SNP and 1.9 non-polymorphic probes present on the Affymetrix CytoScan HD array. Samples were separated by affection status. Eight unaffected and 5 affected samples from across 3 families were analyzed. Analysis was performed using the Affymetrix Chromosome Analysis Suite (ChAS) v.2.0 software.
2014-06-04 | E-GEOD-50573 | biostudies-arrayexpress
Project description:The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo an MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm.
2019-06-13 | GSE121680 | GEO