scholarly journals The Drosophila Post-mating Response: Gene Expression and Behavioral Changes Reveal Perdurance and Variation in Cross-Tissue Interactions

2020 ◽  
Vol 10 (3) ◽  
pp. 967-983 ◽  
Author(s):  
Nicole R. Newell ◽  
Surjyendu Ray ◽  
Justin E. Dalton ◽  
Julia C. Fortier ◽  
Joyce Y. Kao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Wide Association Study ◽  
Wnt Signaling Pathway ◽  
Dna Polymorphisms ◽  
Female Gonad ◽  
Female Head ◽  
Tissue Interactions ◽  
Examine Gene Expression ◽  
A Genome ◽  
The Impact

Examining cross-tissue interactions is important for understanding physiology and homeostasis. In animals, the female gonad produces signaling molecules that act distally. We examine gene expression in Drosophila melanogaster female head tissues in 1) virgins without a germline compared to virgins with a germline, 2) post-mated females with and without a germline compared to virgins, and 3) post-mated females mated to males with and without a germline compared to virgins. In virgins, the absence of a female germline results in expression changes in genes with known roles in nutrient homeostasis. At one- and three-day(s) post-mating, genes that change expression are enriched with those that function in metabolic pathways, in all conditions. We systematically examine female post-mating impacts on sleep, food preference and re-mating, in the strains and time points used for gene expression analyses and compare to published studies. We show that post-mating, gene expression changes vary by strain, prompting us to examine variation in female re-mating. We perform a genome-wide association study that identifies several DNA polymorphisms, including four in/near Wnt signaling pathway genes. Together, these data reveal how gene expression and behavior in females are influenced by cross-tissue interactions, by examining the impact of mating, fertility, and genotype.

scholarly journals Identification of unique venous thromboembolism-susceptibility variants in African-Americans

2017 ◽  
Vol 117 (04) ◽  
pp. 758-768 ◽  
Author(s):  
Sebastian Armasu ◽  
Bryan McCauley ◽  
Iftikhar Kullo ◽  
Hugues Sicotte ◽  
Jyotishman Pathak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Venous Thromboembolism ◽  
African Americans ◽  
Differential Expression ◽  
White Women ◽  
Genome Wide Association Study ◽  
Expression Data ◽  
Significant Differential Expression ◽  
Genome Wide ◽  
A Genome

SummaryTo identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype. Among 393 AA VTE cases and 4,941 AA controls, three intragenic SNPs reached genome-wide significance: LEMD3 rs138916004 (OR=3.2; p=1.3E-08), LY86 rs3804476 (OR=1.8; p=2E-08) and LOC100130298 rs142143628 (OR=4.5; p=4.4E-08); all three SNPs validated using internal cross-validation, parametric bootstrap and meta-analysis methods. LEMD3 rs138916004 and LOC100130298 rs142143628 are only present in Africans (1000G data). LEMD3 showed a significant differential expression in both NCBI Gene Expression Omnibus (GEO) and the Mayo Clinic gene expression data, LOC100130298 showed a significant differential expression only in the GEO expression data, and LY86 showed a significant differential expression only in the Mayo expression data. LEMD3 encodes for an antagonist of TGF-β-induced cell proliferation arrest. LY86 encodes for MD-1 which down-regulates the pro-inflammatory response to lipopolysaccharide; LY86 variation was previously associated with VTE in white women; LOC100130298 is a non-coding RNA gene with unknown regulatory activity in gene expression and epigenetics.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Identification of novel sources of resistance to ascochyta blight in a collection of wild Cicer accessions

2020 ◽  
Author(s):  
Toby E. Newman ◽  
Silke Jacques ◽  
Christy Grime ◽  
Fiona L. Kamphuis ◽  
Robert C. Lee ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Ascochyta Blight ◽  
Ascochyta Rabiei ◽  
Sources Of Resistance ◽  
Highly Pathogenic ◽  
Cicer Echinospermum ◽  
Genome Wide ◽  
A Genome ◽  
The Impact ◽  
Chickpea Cultivars

Chickpea production is constrained worldwide by the necrotrophic fungal pathogen Ascochyta rabiei, the causal agent of ascochyta blight (AB). In order to reduce the impact of this disease, novel sources of resistance are required in chickpea cultivars. Here, we screened a new collection of wild Cicer accessions for AB resistance and identified accessions resistant to multiple, highly pathogenic isolates. In addition to this, analyses demonstrated that some collection sites of Cicer echinospermum harbour predominantly resistant accessions, knowledge that can inform future collection missions. Furthermore, a genome-wide association study identified regions of the Cicer reticulatum genome associated with AB resistance and investigation of these regions identified candidate resistance genes. Taken together, these results can be utilised to enhance the resistance of chickpea cultivars to this globally yield-limiting disease.

scholarly journals Network analysis uncovers putative genes affecting resistance to tick infestation in Braford cattle skin

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Daniela D. Moré ◽  
Fernando F. Cardoso ◽  
Maurício A. Mudadu ◽  
Wilson Malagó-Jr ◽  
Claudia C. Gulias-Gomes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Tick Infestation ◽  
Wnt Signaling Pathway ◽  
Functional Enrichment ◽  
A Genome ◽  
Genetic Mechanisms ◽  
Different Levels

Abstract Background Genetic resistance in cattle is considered a suitable way to control tick burden and its consequent losses for livestock production. Exploring tick-resistant (R) and tick-susceptible (S) hosts, we investigated the genetic mechanisms underlying the variation of Braford resistance to tick infestation. Skin biopsies from four-times-artificially infested R (n = 20) and S (n = 19) hosts, obtained before the first and 24 h after the fourth tick infestation were submitted to RNA-Sequencing. Differential gene expression, functional enrichment, and network analysis were performed to identify genetic pathways and transcription factors (TFs) affecting host resistance. Results Intergroup comparisons of hosts before (Rpre vs. Spre) and after (Rpost vs. Spost) tick infestation found 51 differentially expressed genes (DEGs), of which almost all presented high variation (TopDEGs), and 38 were redundant genes. Gene expression was consistently different between R and S hosts, suggesting the existence of specific anti-tick mechanisms. In the intragroup comparisons, Rpost vs. Rpre and Spost vs. Spre, we found more than two thousand DEGs in response to tick infestation in both resistance groups. Redundant and non-redundant TopDEGs with potential anti-tick functions suggested a role in the development of different levels of resistance within the same breed. Leukocyte chemotaxis was over-represented in both hosts, whereas skin degradation and remodeling were only found in TopDEGs from R hosts. Also, these genes indicated the participation of cytokines, such as IL6 and IL22, and the activation of Wingless (WNT)-signaling pathway. A central gene of this pathway, WNT7A, was consistently modulated when hosts were compared. Moreover, the findings based on a genome-wide association study (GWAS) corroborate the prediction of the WNT-signaling pathway as a candidate mechanism of resistance. The regulation of immune response was the most relevant pathway predicted for S hosts. Members of Ap1 and NF-kB families were the most relevant TFs predicted for R and S, respectively. Conclusion This work provides indications of genetic mechanisms presented by Braford cattle with different levels of resistance in response to tick infestation, contributing to the search of candidate genes for tick resistance in bovine.

scholarly journals A genome-wide association study to identify candidate genes for metabolic disorders in offspring by in vitro fertilization

2021 ◽  
Author(s):  
Lihong Liu ◽  
Siyao Ha ◽  
Zhiling Li ◽  
MingQing Li
Keyword(s):  
Lipid Metabolism ◽  
In Vitro Fertilization ◽  
Health Risks ◽  
Genome Wide Association Study ◽  
Vitro Fertilization ◽  
A Genome ◽  
Offspring Health ◽  
The Impact

Abstract In vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. We conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. We identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, confirmed a conserved motif, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. The impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.

scholarly journals Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic

2019 ◽  
Vol 116 (30) ◽  
pp. 14995-15000 ◽  
Author(s):  
Justyna Cholewa-Waclaw ◽  
Ruth Shah ◽  
Shaun Webb ◽  
Kashyap Chhatbar ◽  
Bernard Ramsahoye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rett Syndrome ◽  
Transcription Initiation ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
A Genome ◽  
The Impact

Patterns of gene expression are primarily determined by proteins that locally enhance or repress transcription. While many transcription factors target a restricted number of genes, others appear to modulate transcription levels globally. An example is MeCP2, an abundant methylated-DNA binding protein that is mutated in the neurological disorder Rett syndrome. Despite much research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved. Here, we integrate quantitative, multidimensional experimental analysis and mathematical modeling to indicate that MeCP2 is a global transcriptional regulator whose binding to DNA creates “slow sites” in gene bodies. We hypothesize that waves of slowed-down RNA polymerase II formed behind these sites travel backward and indirectly affect initiation, reminiscent of defect-induced shockwaves in nonequilibrium physics transport models. This mechanism differs from conventional gene-regulation mechanisms, which often involve direct modulation of transcription initiation. Our findings point to a genome-wide function of DNA methylation that may account for the reversibility of Rett syndrome in mice. Moreover, our combined theoretical and experimental approach provides a general method for understanding how global gene-expression patterns are choreographed.

scholarly journals Mendelian randomization identifies folliculin expression as a mediator of diabetic retinopathy

2020 ◽  
Author(s):  
Andrew D. Skol ◽  
Segun C. Jung ◽  
Ana Marija Sokovic ◽  
Siquan Chen ◽  
Sarah Fazal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetic Retinopathy ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Susceptibility Gene ◽  
Glucose Response ◽  
Aberrant Expression ◽  
Genome Wide ◽  
A Genome

AbstractThe goal of the study was to identify genes whose aberrant expression can contribute to diabetic retinopathy. We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes (T1D) with and without retinopathy. Those genes exhibiting the largest difference in glucose response between individuals with diabetes with and without retinopathy were assessed for association to diabetic retinopathy utilizing genotype data from a genome-wide association study meta-analysis. All genetic variants associated with gene expression (expression Quantitative Trait Loci, eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the eQTLs from the glucose response genes among small association p-values and identified folliculin (FLCN) as a susceptibility gene for diabetic retinopathy. We show that expression of FLCN in response to glucose was greater in individuals with diabetic retinopathy compared to individuals with diabetes without retinopathy. Three large, independent cohorts of individuals with diabetes revealed an association of FLCN eQTLs to diabetic retinopathy. Mendelian randomization further confirmed a direct positive effect of increased FLCN expression on retinopathy in individuals with diabetes. Together, our studies integrating genetic association and gene expression implicate FLCN as a disease gene for diabetic retinopathy.

scholarly journals Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Andrew D Skol ◽  
Segun C Jung ◽  
Ana Marija Sokovic ◽  
Siquan Chen ◽  
Sarah Fazal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetic Retinopathy ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Susceptibility Gene ◽  
Glucose Response ◽  
Genome Wide ◽  
A Genome ◽  
Differential Gene

We determined differential gene expression in response to high glucose in lymphoblastoid cell lines derived from matched individuals with type 1 diabetes with and without retinopathy. Those genes exhibiting the largest difference in glucose response were assessed for association with diabetic retinopathy in a genome-wide association study meta-analysis. Expression quantitative trait loci (eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the eQTLs from the glucose response genes among small association p-values and identified folliculin (FLCN) as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose was greater in individuals with diabetic retinopathy. Independent cohorts of individuals with diabetes revealed an association of FLCN eQTLs with diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy. Integrating genetic association with gene expression implicated FLCN as a disease gene for diabetic retinopathy.

scholarly journals A Genome-Wide Association Study To Identify Candidate Genes for Metabolic Disorders in Offspring by In Vitro Fertilization

2021 ◽  
Author(s):  
Lihong Liu ◽  
Siyao Ha ◽  
Zhiling Li ◽  
MingQing Li
Keyword(s):  
Lipid Metabolism ◽  
In Vitro Fertilization ◽  
Health Risks ◽  
Genome Wide Association Study ◽  
Vitro Fertilization ◽  
A Genome ◽  
Offspring Health ◽  
The Impact

Abstract In vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. We conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. We identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, confirmed a conserved motif, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. The impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.

scholarly journals Article A Genome-Wide Association Study To Identify Candidate Genes for Metabolic Disorders in Offspring by In Vitro Fertilization

2021 ◽  
Author(s):  
Lihong Liu ◽  
Siyao Ha ◽  
Zhiling Li ◽  
MingQing Li
Keyword(s):  
Lipid Metabolism ◽  
In Vitro Fertilization ◽  
Health Risks ◽  
Genome Wide Association Study ◽  
Vitro Fertilization ◽  
A Genome ◽  
Offspring Health ◽  
The Impact

Abstract Background In vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. Methods We conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. Results We identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, confirmed a conserved motif, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. Conclusion The impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.

scholarly journals A genome-wide association study to identify candidate genes for metabolic disorders in offspring by in vitro fertilization

2021 ◽  
Author(s):  
Lihong Liu ◽  
Siyao Ha ◽  
MingQing Li ◽  
Zhiling Li
Keyword(s):  
Lipid Metabolism ◽  
In Vitro Fertilization ◽  
Health Risks ◽  
Genome Wide Association Study ◽  
Vitro Fertilization ◽  
A Genome ◽  
Offspring Health ◽  
The Impact

Abstract Background: In vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. Methods: We conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. Results: We identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. Conclusions: The impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.

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