Peromyscus maniculatus Genetic Variant Analysis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Peromyscus Maniculatus Bairdii
SUBMITTER: University of South Carolina (Columbia) - Department of Drug Discovery and Biomedical Sciences
PROVIDER: PRJEB41333 | EVA | 2020-11-16
REPOSITORIES: EVA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE28239: Identification and functional impact of genomic copy number variants in zebrafish, an important human disease model (Zebrafish Strain CNVs) (expression array) GSE28276: Identification and functional impact of genomic copy number variants in zebrafish, an important human disease model (Zebrafish Strain CNVs) (CGH ZV81M) GSE28278: Identification and functional impact of genomic copy number variants in zebrafish, an important human disease model (Zebrafish Strain CNVs) (CGH ZV81M 2) GSE33962: Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis (CGH) Refer to individual Series
2011-12-27 | E-GEOD-28328 | biostudies-arrayexpress
Project description:Background. Patients with congenital heart disease are identified in 1% of live births, and with improved surgical intervention many patients now survive to adulthood, the corollary of which is increased mortality in the over-65-year-old CHD population. In the clinic, genetic sequencing increasingly identifies novel genetic variants in genes related to congenital heart disease (CHD). Traditional assays for interpreting novel genetic variants are often limited by gene-specificity, whereas animal models are cumbersome and may not accurately reflect human disease. This study investigates CRISPR gene editing in induced pluripotent stem cells and cardiomyocyte-directed differentiation as a human disease model to investigate novel genetic variants identified in association with CHD. Methods and Results. The GATA4 p.Arg284His genetic variant was introduced into iPSCs using high efficiency CRISPR gene editing with homology-directed repair. GATA4 genetic variant and isogenic control cell pairs were selected and differentiated into cardiomyocytes. Expression of the GATA4 p.Arg284His variant resulted in altered calcium transient’s indicative of CHD and consistent with the patient’s clinical phenotype. Transcriptomics revealed molecular and cellular pathway changes in cardiac development, calcium handling, and energy metabolism that contribute to disease aetiology and mechanism, and identified potential treatments that could restore normal cell function. Conclusion. Directed differentiation of iPSCs harbouring the GATA4 p.Arg284His genetic variant recapitulated the CHD phenotype, indicated disease mechanisms, and pointed to potential treatments. The study highlights the utility of transcriptomics for the functional interpretation of cardiac genetic variants and is an exemplar for precision medicine approaches for the investigation of CHD.
2026-02-11 | GSE305687 | GEO
Project description:Oncogenic fusions of EML4 and ALK occur in ~5% of lung adenocarcinomas. EML4- ALK variants have distinct breakpoints within EML4, but the functional differences among these variants remain poorly understood. Here we use CRISPR/Cas9 somatic genome editing to generate autochthonous mouse models of the two most common EML4-ALK variants and show that V3 is more oncogenic than V1. By employing multiplexed genome editing and quantifying the effects of 29 putative tumor suppressor genes on V1- and V3-driven lung cancer growth in vivo we show that many tumor suppressor genes have dramatically variant-specific effects on tumorigenesis. Pharmacogenomic analyses suggest that tumor genotype can also modify responses to therapy. Analysis of a large human EML4-ALK lung cancer cohort identified differences in the genomic landscape depending on the EML4-ALK variant. These findings demonstrate functional heterogeneity between EML4-ALK variants, suggesting that EML4-ALK variants behave more like distinct oncogenes than a uniform entity. More broadly, these findings highlight the dramatic impact of oncogenic fusions partner proteins and coincident tumor suppressor gene alterations on the biology of oncogenic fusion driven cancer.
2025-08-06 | GSE301214 | GEO
Project description:Background. Patients with congenital heart disease are identified in 1% of live births, and with improved surgical intervention many patients now survive to adulthood, the corollary of which is increased mortality in the over-65-year-old CHD population. In the clinic, genetic sequencing increasingly identifies novel genetic variants in genes related to congenital heart disease (CHD). Traditional assays for interpreting novel genetic variants are often limited by gene-specificity, whereas animal models are cumbersome and may not accurately reflect human disease. This study investigates CRISPR gene editing in induced pluripotent stem cells and cardiomyocyte-directed differentiation as a human disease model to investigate novel genetic variants identified in association with CHD. Methods and Results. The GATA4 p.Arg284His genetic variant was introduced into iPSCs using high efficiency CRISPR gene editing with homology-directed repair. GATA4 genetic variant and isogenic control cell pairs were selected and differentiated into cardiomyocytes. Expression of the GATA4 p.Arg284His variant resulted in altered calcium transient’s indicative of CHD and consistent with the patient’s clinical phenotype. Transcriptomics revealed molecular and cellular pathway changes in cardiac development, calcium handling, and energy metabolism that contribute to disease aetiology and mechanism, and identified potential treatments that could restore normal cell function. Conclusion. Directed differentiation of iPSCs harbouring the GATA4 p.Arg284His genetic variant recapitulated the CHD phenotype, indicated disease mechanisms, and pointed to potential treatments. The study highlights the utility of transcriptomics for the functional interpretation of cardiac genetic variants and is an exemplar for precision medicine approaches for the investigation of CHD.
2026-02-11 | GSE305730 | GEO
Project description:We describe a more detailed survey undertaken to detect candidate CNVs in a panel of 20 Asian cultivated rice and the genome-wide characteristics of CNVs in subspecies and groups. These resources allowed us to analyze genetic structure as indicated by CNVs, to implicate the biological roles of CNVs, and to identify candidate CNVs that are likely to occur independently in groups and contribute to differences between the subspecies.
2014-01-01 | GSE42769 | GEO
Project description:Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) with a complex etiology involving environmental and genetic factors. Numerous genetic risk loci for MS have been nominated through genome-wide association studies, with most associated variants residing in non-coding regions. However, further work is needed to understand how genetic variation contributes to disease-related alterations to gene expression. Here, we use massively parallel reporter assays (MPRAs) to identify genetic risk variants with genotype-dependent enhancing or silencing activity within a set of 14,276 variants distributed among 233 independent multiple sclerosis risk loci that have reached genome-wide or suggestive significance. We applied our MPRA library to a commercially available B cell line (GM12878) as well as B cell lines derived from two patients with MS. In total, our approach discovered 150 allelic enhancer variants and 286 allelic silencing variants, representing 83 independent MS risk loci. Collectively, our systematic, genome-scale approach implicates causal genotype-dependent gene regulatory mechanisms for 38% of the known or suggestive MS risk loci, providing a unique resource for the discovery of the genetic mechanisms underlying this chronic inflammatory disease.
2025-11-13 | GSE293036 | GEO