Po CLEC4a
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB29890 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In this dataset, we include the gene expression and exon splicing variants of two Ewing sarcoma cell lines (RDES and TC-32) after knockdown of the transcription factor SOX6 in order to obtain differentially expressed genes and different exon splicing variants.
2020-04-01 | GSE120576 | GEO
Project description:Humans co-existed and interbred with other hominins which later became extinct. These archaic hominins are known to us only through fossil records and for two cases, genome sequences. Here we engineer Neanderthal and Denisovan sequences into thousands of artificial genes to reconstruct the pre-mRNA processing patterns of these extinct populations. Of the 5,224 alleles tested in this massively parallel splicing reporter assay (MaPSy), we report 969 exonic splicing mutations (ESMs) that correspond to differences in exon recognition between extant and extinct hominins. Using MaPSy splicing variants, predicted splicing variants, and splicing quantitative trait loci, we show that splice-disrupting variants experienced greater purifying selection in anatomically modern humans than in Neanderthals. Adaptively introgressed variants were enriched for moderate effect splicing variants, consistent with positive selection for alternative spliced alleles following introgression. As particularly compelling examples, we characterized a novel tissue-specific alternative splicing variant at the adaptively introgressed innate immunity gene TLR1, as well as a novel Neanderthal introgressed alternative splicing variant in the gene HSPG2 that encodes perlecan. We further identified potentially pathogenic splicing variants found only in Neanderthals and Denisovans in genes related to sperm maturation and immunity. Finally, we found splicing variants that may contribute to variation among modern humans in total bilirubin, balding, hemoglobin levels, and lung capacity. Our findings provide novel insights into natural selection acting on splicing in human evolution and demonstrate how functional assays can be used to identify candidate causal variants underlying differences in gene regulation and phenotype.
2022-10-07 | GSE201856 | GEO
Project description:Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pre-transplant genetic susceptibility is evident in adult TA-TMA patients at the level of TMA-associated variants and further investigated the association of genetic variants with clinical outcomes. We studied 30 patients with TA-TMA at a median of 73 (9-540) post-transplant days, donors of 18/30 patients and 30 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pre-transplant peripheral blood was analyzed by targeted next generation sequencing for complement regulatory genes and ADAMTS13. Donors presented significantly lower frequency of rare variants (p=0.049) and variants in exonic/splicing/UTR regions (p=0.025), compared to TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13 (p=0.001), CD46 (p=0.002), CFH (p=0.010) and CFI (p=0.031). Pathogenic variants were found in ADAMTS13, CFH, CFI and CFB, while homozygous pathogenic variants in ADAMTS13 and CFB were evident in only 4 TA-TMA patients (p=0.038). Patients refractory to conventional treatment (70%) were significantly (p=0.045) enriched for variants in exonic/splicing/UTR regions compared to responders. Nineteen of 30 patients (63%) succumbed to transplant-related mortality, which was also associated with significantly (p=0.012) increased frequency of variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pre-transplant genomic screening may be useful to intensify monitoring and early intervention in high-risk patients.
2019-04-18 | E-MTAB-7848 | biostudies-arrayexpress
Project description:It is estimated that 10-30% of disease-associated genetic variants affect splicing. Splicing variants may generate deleteriously altered gene product and are potential therapeutic targets. However, experimental diagnosis for splicing variants is time-consuming and reliable computational prediction tools have not been established, especially for the 3’ end of introns. The major challenge lies in the redundant and ill-defined branch site motif therein. Here, we carried out unbiased massively parallel splicing assays on 5,307 disease-associated variants overlapped with branch sites. We observed that 11.0% (455 out of 4,154 valid comparisons) of candidate variants showed a consistent pattern of altered splicing across four experimental replicates, among which 244 candidates (6.1%) presented more than two-fold changes in the use of noncanonical splice sites and these are named high-confidence (HC) significant candidates.
2022-05-10 | GSE179892 | GEO
Project description:MicroRNAs (miRNAs) are small non-coding regulatory RNAs that play key roles in many diverse biological processes such as spermatogenesis. However, no study has been performed on the miRNA transcriptome of developing porcine testes. Here, we employed Solexa deep sequencing technology to extend the repertoire of porcine testis miRNAs and extensively compare the expression patterns of the sexually immature and mature porcine testes. Solexa sequencing of two small RNA libraries derived from immature (30 days) and mature (180 days) pig testis samples yielded over 25 million high-quality reads. Overall, the two developmental stages had significantly different small RNA compositions. A custom data analysis pipeline identified 398 known and/or homologous conserved porcine miRNAs, 15 novel pig-specific miRNAs, and 56 novel candidate miRNAs. We further observed multiple mature miRNA variants (isomiRs) and identified a new bidirectional transcribed miRNA locus, ssc-mir-181a. One hundred twenty-two miRNAs were differentially expressed in the immature and mature testes, and 10 were validated using quantitative RT-PCR. Furthermore, GO and KEGG pathway analyses of the predicted miRNA targets further illustrate the likely roles for these differentially expressed miRNAs in spermatogenesis. This study is the first comparative profile of the miRNA transcriptome in immature and mature porcine testes using a deep sequencing approach, and it provides a useful resource for future studies on the role of miRNAs in spermatogenesis and male infertility treatment.
2011-09-23 | GSE28169 | GEO
Project description:Pig is an important animal model for human obesity and diseases. However, the complexity of the porcine transcriptome is not yet fully elucidated. Here we have used massively parallel high-throughput sequencing of cDNA (RNA-Seq) to generate a high-resolution map of the porcine transcriptome and miRNA in liver (LI), longissimus dorsi (LD) and abdominal fat (AF) from an F2 female full-sib pair with extreme phenotypes in growth and fat deposit. On the basis of the porcine annotated genes against the UCSC database, we identified 21,414 annotated genes in our RNA-Seq analysis and 48,045-122,931 novel transcript fragments, which could be clustered into 17,085-29,499 novel transcriptional active regions (nTARs). We found that ~18.8% of the detected known genes showed alternative splicing patterns, and alternative 3’ splicing was the most common type of alternative splicing events in pigs. We also detected that more than 22.7% of the known genes identified here were extended at their 5’ and/or 3’ end. We identified 2,796, 1,551 and 835 differentially expressed genes (DEGs), respectively, in AF, LI and LD between the two individuals. Examining the complexity of the pig transcriptome in three organs (liver, abdominal fat, longissimus dorsi muscle) from a female full-sib pair.
2011-01-12 | E-GEOD-26382 | biostudies-arrayexpress
Project description:Using a high throughput splicing reporter assay, we tested 1,080 single nucleotide variants in POU1F1, a key transcription factor essential for pituitary development. Our saturation splicing effect map identifies 96 splice disruptive variants, including 14 synonymous variants, of which 8 were found in unrelated patients diagnosed with hypopituitarism.
2021-04-22 | GSE172504 | GEO
Project description:Pig is an important animal model for human obesity and diseases. However, the complexity of the porcine transcriptome is not yet fully elucidated. Here we have used massively parallel high-throughput sequencing of cDNA (RNA-Seq) to generate a high-resolution map of the porcine transcriptome and miRNA in liver (LI), longissimus dorsi (LD) and abdominal fat (AF) from an F2 female full-sib pair with extreme phenotypes in growth and fat deposit. On the basis of the porcine annotated genes against the UCSC database, we identified 21,414 annotated genes in our RNA-Seq analysis and 48,045-122,931 novel transcript fragments, which could be clustered into 17,085-29,499 novel transcriptional active regions (nTARs). We found that ~18.8% of the detected known genes showed alternative splicing patterns, and alternative 3’ splicing was the most common type of alternative splicing events in pigs. We also detected that more than 22.7% of the known genes identified here were extended at their 5’ and/or 3’ end. We identified 2,796, 1,551 and 835 differentially expressed genes (DEGs), respectively, in AF, LI and LD between the two individuals.
2011-01-12 | GSE26382 | GEO
Project description:How plants control the transition to flowering in response to ambient temperature is only beginning to be understood. In Arabidopsis thaliana, the MADS-box transcription factor genes FLOWERING LOCUS M (FLM) and SHORT VEGETATIVE PHASE (SVP) have key roles in this process. FLM is subject to temperature-dependent alternative splicing, producing two splice variants, FLM-M-NM-2 and FLM-M-NM-4, which compete for interaction with the floral repressor SVP. The SVP/FLM-M-NM-2 complex is predominately formed at low temperatures and prevents precocious flowering. In contrast, the competing SVP FLM-M-NM-4 complex is impaired in DNA binding and acts as a dominant negative activator of flowering at higher temperatures. Our results demonstrate the importance of temperature-dependent alternative splicing in modulating the timing of the floral transition in response to environmental change. ChIP-seq A. thaliana FLM (3 replicates for gFLM and 2 replicates for FLM splice variants)
2013-09-19 | E-GEOD-48082 | biostudies-arrayexpress
Project description:Background: Substantial progress has been made in the identification of sequence elements that control mRNA splicing and the genetic variants in these elements that alter mRNA splicing (referred to as splicing quantitative trait loci -- sQTLs). Genetic variants that affect mRNA splicing in trans are harder to identify because their effects can be more subtle and diffuse, and the variants are not co-located with their targets. We carried out a transcriptome-wide analysis of the effects of a mutation in a ubiquitous splicing factor that causes retinitis pigmentosa (RP) on mRNA splicing, using exon microarrays. Results: Exon microarray data was generated from whole blood samples obtained from four individuals with a mutation in the splicing factor PRPF8 and four sibling controls. Although the mutation has no known phenotype in blood, there was evidence of widespread differences in splicing between cases and controls (affecting between 10\% and 25\% of exons). Most probesets with significantly different inclusion (defined as the expression intensity of the exon divided by the expression of the corresponding transcript) between cases and controls had higher inclusion in cases and corresponded to exons that were shorter than average, AT-rich, located towards the 5' end of the gene and flanked by long introns. Introns flanking affected probesets were particularly depleted for the shortest category of introns, associated with splicing via intron definition. Conclusions: Our results show that a mutation in a splicing factor, with a phenotype that is restricted to retinal tissue, acts as a trans-sQTL cluster in whole blood samples. Characteristics of the affected exons suggest that they are spliced co-transcriptionally and via exon definition. Eight samples consisting of four sibling pairs were analysed. One individual in each pair harboured an RP-causing mutation on the PRPF8 gene (cases). Unaffected siblings were used as controls.
2012-12-25 | E-GEOD-43134 | biostudies-arrayexpress