Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA395399 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:CIDR: Uncovering the genetic architecture of colorectal cancer with focus of rare and less frequent variants
| PRJNA395398 | ENA
Project description:CIDR: Detecting Common and Rare Genetic Loci and GxE Interactions in Colorectal Cancer
| PRJNA377382 | ENA
Project description:CIDR: Detecting Common and Rare Genetic Loci and GxE Interactions in Colorectal Cancer
| PRJNA377381 | ENA
Project description:Understanding the function of rare non-coding genetic variants represents a significant challenge. Here, we developed MapUTR, a screen to identify rare 3’ UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated a further interrogation of 11,929 cancer somatic mutations, uncovering 3,928 (33%) functional mutations in well-established cancer driver genes, such as CDKN2A. Functional MapUTR variants were enriched in miRNA targets and protein-RNA interaction sites. Based on MapUTR, we define a new metric, untranslated tumor mutation burden (uTMB), reflecting the amount of somatic functional MapUTR variants of a tumor. We showed the potential of uTMB in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), illustrating their cancer-driving potential. Our study elucidates the function of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.
2024-02-06 | GSE232572 | GEO
Project description:Understanding the function of rare non-coding genetic variants represents a significant challenge. Here, we developed MapUTR, a screen to identify rare 3’ UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated a further interrogation of 11,929 cancer somatic mutations, uncovering 3,928 (33%) functional mutations in well-established cancer driver genes, such as CDKN2A. Functional MapUTR variants were enriched in miRNA targets and protein-RNA interaction sites. Based on MapUTR, we define a new metric, untranslated tumor mutation burden (uTMB), reflecting the amount of somatic functional MapUTR variants of a tumor. We showed the potential of uTMB in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), illustrating their cancer-driving potential. Our study elucidates the function of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.
2024-02-06 | GSE232571 | GEO
Project description:Understanding the function of rare non-coding genetic variants represents a significant challenge. Here, we developed MapUTR, a screen to identify rare 3’ UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated a further interrogation of 11,929 cancer somatic mutations, uncovering 3,928 (33%) functional mutations in well-established cancer driver genes, such as CDKN2A. Functional MapUTR variants were enriched in miRNA targets and protein-RNA interaction sites. Based on MapUTR, we define a new metric, untranslated tumor mutation burden (uTMB), reflecting the amount of somatic functional MapUTR variants of a tumor. We showed the potential of uTMB in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), illustrating their cancer-driving potential. Our study elucidates the function of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.
2024-02-06 | GSE232570 | GEO
Project description:Natural populations of the fruit fly, Drosophila melanogaster, segregate genetic variation that leads to cardiac disease phenotypes. Drosophila is well-known as a model for studying the mechanisms by which human disease genes cause pathology, including heart disease, but it is less well appreciated that they may also model the genetic architecture of disease, since flies presumably also have diseases that have a genetic basis. It is reasoned that most of these aberrant inbred line effects would be due to capture of rare variants of large effect as homozygotes, allowing the variants to be mapped rapidly using contemporary genomic approaches. In order to map the genetic variants in flies, we used single feature polymorphism (SFP) analysis to contrast the genome-wide genotype frequencies between pools of flies with aberrant and normal heart phenotype. SFP analysis is an indirect method for genome-wide genotyping that utilizes differential hybridization of genomic DNA to probes on a DNA chip that was initially designed for gene expression profiling, but can be used for species where genotyping chips are not available.
2013-03-15 | GSE45123 | GEO
Project description:Natural populations of the fruit fly, Drosophila melanogaster, segregate genetic variation that leads to cardiac disease phenotypes. Drosophila is well-known as a model for studying the mechanisms by which human disease genes cause pathology, including heart disease, but it is less well appreciated that they may also model the genetic architecture of disease, since flies presumably also have diseases that have a genetic basis. It is reasoned that most of these aberrant inbred line effects would be due to capture of rare variants of large effect as homozygotes, allowing the variants to be mapped rapidly using contemporary genomic approaches. In order to map the genetic variants in flies, we used single feature polymorphism (SFP) analysis to contrast the genome-wide genotype frequencies between pools of flies with aberrant and normal heart phenotype. SFP analysis is an indirect method for genome-wide genotyping that utilizes differential hybridization of genomic DNA to probes on a DNA chip that was initially designed for gene expression profiling, but can be used for species where genotyping chips are not available. DNA was prepared from three independent pools of 15 flies for each of the two types, as well as from the two parental lines. The samples were sheared and labeled with biotin, then hybridized to Affymetrix Drosophila expression microarray chips. Mismatch hybridization, namely a significant difference in the hybridization intensity between the parental lines, was detected from all perfect match (PM) probes, located in over 9,000 probes with an estimated False Discovery Rate of 11%.
2013-03-15 | E-GEOD-45123 | biostudies-arrayexpress
Project description:In psychiatric disorders, common and rare genetic variants cause widespread dysfunction of cells and their interactions, especially in the prefrontal cortex, giving rise to psychiatric symptoms. To better understand these processes, we traced the effects of common and rare genetics, and cumulative disease risk scores, to their molecular footprints in human cortical single-cell types. We demonstrated that examining gene expression at single-exon resolution is crucial for understanding the cortical dysregulation associated with diagnosis and genetic risk derived from common variants. We then used disease risk scores to identify a core set of genes that serve as a footprint of common and rare variants in the cortex. Pathways enriched in these genes included dopamine regulation, circadian entrainment, and hormone regulation. Single-nuclei-RNA-sequencing pinpointed these enriched genes to excitatory cortical neurons. This study highlights the importance of studying sub-gene-level genetic architecture to classify psychiatric disorders based on biology rather than symptomatology, to identify novel targets for treatment development.
2022-11-17 | GSE208338 | GEO
Project description:Background & Aims: Most inflammatory bowel diseases (IBDs) are classic polygenic disorders represented by common alleles. However, multiple determinants of very early-onset IBD characterized by a more extensive disease course remain largely unknown. The present study aimed to define the genetic architecture of pediatric and adult-onset IBDs in the Polish population. Results: Of 82 SNPs validated/replicated for association with IBD, a novel BRD2 (rs1049526) association was found in both pediatric (OR= 2.35) and adult (OR= 2.66) patients. Thirty SNPs were shared between pediatric and adult patients; 22 and 30 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare/infrequent, potentially deleterious variants in IBD-associated or innate immunity-associated genes. Both groups of variants were over-represented in affected children. Two highly deleterious homozygous variants, HLA-DRB1 c.565_566insC and NCF4 p.Arg8Trp, were found in two affected children, and WAS p.Glu131Lys was found in one child and one adult patient. Conclusions: Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare/low frequency deleterious variants in affected children suggests a contribution by yet unexplained genetic components.
2017-01-01 | GSE79094 | GEO