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- Cavalli, Marco, et al.
(författare)
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Studies of liver tissue identify functional gene regulatory elements associated to gene expression, type 2 diabetes, and other metabolic diseases
- 2019
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Ingår i: Human Genomics. - : Springer Science and Business Media LLC. - 1473-9542 .- 1479-7364. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background:Genome-wide association studies (GWAS) of diseases and traits have found associations to gene regions but not the functional SNP or the gene mediating the effect. Difference in gene regulatory signals can be detected using chromatin immunoprecipitation and next-gen sequencing (ChIP-seq) of transcription factors or histone modifications by aligning reads to known polymorphisms in individual genomes. The aim was to identify such regulatory elements in the human liver to understand the genetics behind type 2 diabetes and metabolic diseases.Methods: The genome of liver tissue was sequenced using 10X Genomics technology to call polymorphic positions. Using ChIP-seq for two histone modifications, H3K4me3 and H3K27ac, and the transcription factor CTCF, and our established bioinformatics pipeline, we detected sites with significant difference in signal between the alleles.Results:We detected 2329 allele-specific SNPs (AS-SNPs) including 25 associated to GWAS SNPs linked to liver biology, e.g., 4 AS-SNPs at two type 2 diabetes loci. Two hundred ninety-two AS-SNPs were associated to liver gene expression in GTEx, and 134 AS-SNPs were located on 166 candidate functional motifs and most of them in EGR1-binding sites.Conclusions:This study provides a valuable collection of candidate liver regulatory elements for further experimental validation.
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| 4. |
- Haque, Rehnuma, et al.
(författare)
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Monitoring SARS-CoV-2 variants in wastewater of Dhaka City, Bangladesh : approach to complement public health surveillance systems
- 2023
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Ingår i: Human Genomics. - : Springer Nature. - 1473-9542 .- 1479-7364. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWastewater-based epidemiological surveillance has been considered a powerful tool for early detection and monitoring of the dynamics of SARS-CoV-2 and its lineages circulating in a community. This study is aimed to investigate the complexity of SARS-CoV-2 infection dynamics in Dhaka city by examining its genetic variants in wastewater. Also, the study seeks to determine a connection between the SARS-CoV-2 variations detected in clinical testing and those found in wastewater samples.ResultsOut of 504 samples tested in RT-qPCR, 185 (36.7%) tested positive for SARS-CoV-2 viral RNA. The median log10 concentration of SARS-CoV-2 N gene copies/Liter of wastewater (gc/L) was 5.2, and the median log10 concentration of ORF1ab was 4.9. To further reveal the genetic diversity of SARS-CoV-2, ten samples with ORF1ab real-time RT-PCR cycle threshold (Ct) values ranging from 28.78 to 32.13 were subjected to whole genome sequencing using nanopore technology. According to clade classification, sequences from wastewater samples were grouped into 4 clades: 20A, 20B, 21A, 21J, and the Pango lineage, B.1, B.1.1, B.1.1.25, and B.1.617.2, with coverage ranging from 94.2 to 99.8%. Of them, 70% belonged to clade 20B, followed by 10% to clade 20A, 21A, and 21J. Lineage B.1.1.25 was predominant in Bangladesh and phylogenetically related to the sequences from India, the USA, Canada, the UK, and Italy. The Delta variant (B.1.617.2) was first identified in clinical samples at the beginning of May 2021. In contrast, we found that it was circulating in the community and was detected in wastewater in September 2020.ConclusionEnvironmental surveillance is useful for monitoring temporal and spatial trends of existing and emerging infectious diseases and supports evidence-based public health measures. The findings of this study supported the use of wastewater-based epidemiology and provided the baseline data for the dynamics of SARS-CoV-2 variants in the wastewater environment in Dhaka, Bangladesh.
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| 5. |
- Saddala, Madhu Sudhana, et al.
(författare)
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Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration
- 2019
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Ingår i: Human Genomics. - : BMC. - 1473-9542 .- 1479-7364. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAge-related macular degeneration (AMD) is the most common, progressive, and polygenic cause of irreversible visual impairment in the world. The molecular pathogenesis of the primary events of AMD is poorly understood. We have investigated a transcriptome-wide analysis of differential gene expression, single-nucleotide polymorphisms (SNPs), indels, and simple sequence repeats (SSRs) in datasets of the human peripheral retina and RPE-choroid-sclera control and AMD.Methods and resultsAdaptors and unbiased components were removed and checked to ensure the quality of the data sets. Molecular function, biological process, cellular component, and pathway analyses were performed on differentially expressed genes. Analysis of the gene expression datasets identified 5011 upregulated genes, 11,800 downregulated genes, 42,016 SNPs, 1141 indels, and 6668 SRRs between healthy controls and AMD donor material. Enrichment categories for gene ontology included chemokine activity, cytokine activity, cytokine receptor binding, immune system process, and signal transduction respectively. A functional pathways analysis identified that chemokine receptors bind chemokines, complement cascade genes, and create cytokine signaling in immune system pathway genes (p value amp;lt;0.001). Finally, allele-specific expression was found to be significant for Chemokine (C-C motif) ligand (CCL) 2, 3, 4, 13, 19, 21; C-C chemokine receptor (CCR) 1, 5; chemokine (C-X-C motif) ligand (CXCL) 9, 10, 16; C-X-C chemokine receptor type (CXCR) 6; as well as atypical chemokine receptor (ACKR) 3,4 and pro-platelet basic protein (PPBP).ConclusionsOur results improve our overall understanding of the chemokine receptors signaling pathway in AMD conditions, which may lead to potential new diagnostic and therapeutic targets.
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| 7. |
- Tisato, Veronica, et al.
(författare)
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LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL)
- 2023
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Ingår i: Human Genomics. - : BioMed Central (BMC). - 1473-9542 .- 1479-7364. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity.Results: We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 - 8CG (ferroportin; FPN1), HAMP - 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 - 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54-7.29 and OR = 1.47; 1.02-2.12, respectively). Moreover, LINE-1 methylation was inversely related (r2 = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 - 8CG and HAMP - 582AG genotype stratification (Delta SLC40A1 = + 8.99 dB HL and Delta HAMP = - 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFEC282Y, SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42-0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35-0.76; P = 0.001).Conclusion: Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL.
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- Van den Eynden, Jimmy, 1977, et al.
(författare)
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The genetic structure of the Belgian population
- 2018
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Ingår i: Human Genomics. - : Springer Science and Business Media LLC. - 1473-9542 .- 1479-7364. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: National and international efforts like the 1000 Genomes Project are leading to increasing insights in the genetic structure of populations worldwide. Variation between different populations necessitates access to population-based genetic reference datasets. These data, which are important not only in clinical settings but also to potentiate future transitions towards a more personalized public health approach, are currently not available for the Belgian population. Results: To obtain a representative genetic dataset of the Belgian population, participants in the 2013 National Health Interview Survey (NHIS) were invited to donate saliva samples for DNA analysis. DNA was isolated and single nucleotide polymorphisms (SNPs) were determined using a genome-wide SNP array of around 300,000 sites, resulting in a high-quality dataset of 189 samples that was used for further analysis. A principal component analysis demonstrated the typical European genetic constitution of the Belgian population, as compared to other continents. Within Europe, the Belgian population could be clearly distinguished from other European populations. Furthermore, obvious signs from recent migration were found, mainly from Southern Europe and Africa, corresponding with migration trends from the past decades. Within Belgium, a small north-west to south-east gradient in genetic variability was noted, with differences between Flanders and Wallonia. Conclusions: This is the first study on the genetic structure of the Belgian population and its regional variation. The Belgian genetic structure mirrors its geographic location in Europe with regional differences and clear signs of recent migration.
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