Genome wide analysis of copy number variation in NAFLD spectrum
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE55645 | GEO | 2015/02/26
SECONDARY ACCESSION(S): PRJNA240289
REPOSITORIES: GEO
Similar Datasets
Project description:Despite some success in identifying CNVs responsible for metabolic phenotypes including obesity and diabetes mellitus, there are as yet no data available to suggest whether or not CNVs might be involved in the etiology of the NAFLD spectrum. This report is a comprehensive analysis of copy number in Malaysian patients with NAFLD. Genomic DNA was extracted from blood obtained from patients with NAFLD and submitted for genome-wide analysis using aCGH
2015-02-26 | E-GEOD-55645 | biostudies-arrayexpress
Project description:The Illumina Human Omni2.5 array is a high resolution microarray platform for studying copy number variations in the human genome. It is widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed this platform to investigate the risk factor CNVs in 95 individuals diagnosed with Fetal alcohol spectrum syndrome (FASD). We also examined 87 age-matched individuals with no symptoms of FASD or any neurodevelopmental disorders. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to FASD.
2018-11-21 | GSE102650 | GEO
Project description:Rare DNA copy-number variation (CNV) plays an important role in the underlying genetic etiology of autism and intellectual disability. Although large numbers of copy-number variants (CNVs) have been recently implicated in autism, most are large affecting many genes and specificity of these lesions with respect to classically defined autism as opposed to more broadly defined developmental delay is unclear. We exploited the repeat architecture of the genome to target smaller regions (n=1340 hotspots, median size 15 kbp) flanked by repetitive sequence among 2,240 autism simplex patients and a subset of unaffected parents.
2012-09-30 | GSE39655 | GEO
Project description:Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus and the elderly, impacting 40% of individuals over 70. Regulation of heterochromatin at the nuclear lamina has been associated with aging and age-dependent metabolic changes. We have shown that changes at the lamina in aged hepatocytes and laminopathy models lead to redistribution of lamina-associated domains (LADs), opening of repressed chromatin, and upregulation of genes regulating lipid synthesis and storage, culminating in fatty liver. Here we test the hypothesis that change in expression of lamina-associated proteins and nuclear shape leads to redistribution of LADs, followed by altered binding of pioneer factor FOXA2, uprregulation of lipid synthesis and storage, and culminating in steatosis in younger NAFLD patients (aged 21-51). Changes in nuclear morphology alter LAD partitioning and reduced lamin B1 signal correlates with increased FOXA2 binding prior to severe steatosis in young mice placed on Western det. Nuclear shape is also changed in younger NAFLD patients. LADs are redistrubted and Lamin B1 signal decreases similarly in mild and severe steatosis. In contrast, FOXA2 binding is similar in normal and NAFLD patients with moderate steatosis and is repositioned only in NAFLD patients with more severe lipid accumulation. Hence, changes at the nuclear lamina reshape FOXA2 binding with progression of the disease. Our results suggest a role for nuclear lamina in etiology of NAFLD, irrespective of aging, with potential for improved stratification of patients and novel treatments aimed at restoring nuclear lamina function.
2022-11-10 | GSE197399 | GEO
Project description:Objective: Intellectual disability (ID) is often sporadic, and its complex etiology can make clinical diagnosis difficult. The aims of this study were to detect genomic copy number variations (CNVs) in Chinese patients with ID, and to analyze the correlation between pathogenic CNVs and clinical phenotypes. Methods: After excluding cases of ID caused by chromosomal aneuploidy, metabolic dysfunction, or environmental factors, we enrolled 60 patients with moderate to severe ID. We performed karyotype and single-nucleotide polymorphism (SNP) array analyses for all patients. Finally, we analyzed the relationship between CNVs and phenotype using CNV databases and genotype-phenotype comparisons. Results: Karyotype analysis showed chromosomal terminal abnormalities in five patients and balanced translocations in two patients. Using SNP array analysis for 60 patients, we detected 87 CNVs in 45 patients, which included 16 pathogenic CNVs in 12 patients with a diagnostic yield of 20.0% (12/60). In one patient, we observed 14 regions of homozygosity > 10 Mb to 266 Mb. We detected a large deletion at 16q22.2 or 3q24q25 in each of two patients, in regions that have not previously been associated with specific syndromes. One case carried a 210-kb deletion at 1q21, including only one coding gene, LPPR4, which may be a candidate gene for the ID phenotype. Conclusions: Use of the genome-wide array screening method can improve the detection rate of CNVs, reveal chromosomal abnormalities that have not been well characterized by cytology, and provide a new way to locate genes for patients with the ID phenotype. However, interpretation of CNVs remains a major challenge, which is why we believe that publicly shared data on CNVs and phenotypes can create a rich database of information.
2019-06-15 | GSE83414 | GEO
Project description:Copy-number variants (CNVs) are large-scale amplifications or deletions of DNA that can drive rapid adaptive evolution and result in large-scale changes in gene expression. Whereas alterations in the copy number of one or more genes within a CNV can confer a selective advantage, other genes within a CNV can decrease fitness when their dosage is changed. Dosage compensation - in which the gene expression output from multiple gene copies is less than expected - is one means by which an organism can mitigate the fitness costs of deleterious gene amplification. Previous research has shown evidence for dosage compensation at both the transcriptional level and at the level of protein expression; however, the extent of compensation differs substantially between genes, strains, and studies. Here, we investigated sources of dosage compensation at multiple levels of gene expression regulation by defining the transcriptome, translatome and proteome of experimentally evolved yeast (Saccharomyces cerevisiae) strains containing adaptive CNVs.
2023-11-01 | PXD046587 | Pride
Project description:Non-alcoholic fatty liver disease (NAFLD), alongside the global obesity epidemic, is rapidly emerging as a dominant liver disease etiology that leads to progressive liver fibrosis, its terminal stage, cirrhosis, and hepatocellular carcinoma (HCC). We identified and validated a 133-gene signature (Prognostic Liver Signature for NAFLD [PLS-NAFLD]) to predict long-term HCC risk in patients with NAFLD. By analyzing PLS-NAFLD, IDO1 was identified as a potenial chemopreventive target for HCC from NAFLD. To test this hypothesis, we utilized our clinical-prognostic-signature-inducible cell culture model. We first confirmed that free fatty acid treatment (800 μM oleic acid and 400 μM palmitic acid) can induce PLS-NAFLD, then IDO1 inhibitor, epacadostat, can reverse the high-risk pattern in a dose-dependent manner.
2022-07-01 | GSE200460 | GEO
Project description:Intra-specific polymorphism in copy number is documented in many organisms, including human and chimpanzee, but very little is known for other great apes. This study aims to provide CNVs data for orangutan, gorilla, bonobo and chimpanzee, and compare the CNV patterns among these species, as well as with human CNVs and segmental duplications from public databases.
2011-08-03 | GSE30559 | GEO
Project description:Purpose: Obesity is known to be a multifactorial condition that is highly heritable. There have been ~60 susceptibility loci identified, but they only account for a fraction of cases. As copy number variations (CNVs) have been implicated in the etiology of a multitude of human disorders including obesity, here, we investigated the contribution of rare CNVs (<0.1% population frequency) in pediatric cases of obesity. Methods: We genotyped 67 pediatric patients presenting with obesity, including 22 with co-morbid developmental delay and prioritized rare CNVs at known associated loci, as well as, those impacting genes involved in energy homeostasis or related processes. Results: We identified clinically relevant or potentially clinically-relevant CNVs in 15% (10/67) of individuals. Of these, 4% (3/67) had 16p11.2 microdeletions encompassing the known obesity risk gene SH2B1. Notably, we identified two unrelated probands harboring different 6p22.2 microduplications encompassing SCGN, a potential novel candidate gene for obesity. Further, we identified other biologically relevant candidate genes for pediatric obesity including ARID5B, GPR39, PTPRN2, and HNF4G. Conclusion: We found previously reported candidate loci for obesity, and new ones, suggesting CNV analysis may assist in the diagnosis of pediatric obesity.
2018-07-12 | GSE101414 | GEO
Project description:Purpose: Obesity is known to be a multifactorial condition that is highly heritable. There have been ~60 susceptibility loci identified, but they only account for a fraction of cases.. As copy number variations (CNVs) have been implicated in the etiology of a multitude of human disorders including obesity, here, we investigated the contribution of rare CNVs (<0.1% population frequency) in pediatric cases of obesity. Methods: We genotyped 67 pediatric patients presenting with obesity, including 22 with co-morbid developmental delay and prioritized rare CNVs at known associated loci, as well as, those impacting genes involved in energy homeostasis or related processes. Results: We identified clinically relevant or potentially clinically-relevant CNVs in 15% (10/67) of individuals. Of these, 4% (3/67) had 16p11.2 microdeletions encompassing the known obesity risk gene SH2B1. Notably, we identified two unrelated probands harboring different 6p22.2 microduplications encompassing SCGN, a potential novel candidate gene for obesity. Further, we identified other biologically relevant candidate genes for pediatric obesity including ARID5B, GPR39, PTPRN2, and HNF4G. Conclusion: We found previously reported candidate loci for obesity, and new ones, suggesting CNV analysis may assist in the diagnosis of pediatric obesity.
2018-07-12 | GSE101416 | GEO