scholarly journals The Loss of 1p as a Reliable Marker of Progression in a Child with Aggressive Meningioma: A 16-Year Follow-Up Case Report

2020 ◽  
pp. 1-8
Author(s):  
Sina Hemmer ◽  
Christoph Sippl ◽  
Felix Sahm ◽  
Joachim Oertel ◽  
Steffi Urbschat ◽  
...  
Keyword(s):  
Chromosome 1 ◽  
Molecular Characteristics ◽  
Genetic Characteristics ◽  
Tumor Specimen ◽  
Potential Marker ◽  
Genome Wide ◽  
A Genome ◽  
History Of ◽  
Reliable Marker

<b><i>Background:</i></b> Here, we present the case of a 32-year-old female with a progressing history of meningioma for 16 years starting with an ethmoidal lesion in 2002. The initial tumor specimen of this patient showed a deletion of the short arm of chromosome 1 through a translocation between chromosomes 1 and 11 (t[1; 11]) as well as additional chromosomal aberrations, including partial or complete monosomy of chromosomes 2, 6, 7, 11, 13, and 22. These molecular characteristics were already known to be associated with an aggressive course of the disease, and the patient was, therefore, included in a strict follow-up regime. From 2003 to 2019, the patient suffered multiple relapses and consecutive tumor resections. <b><i>Methods:</i></b> Tumor specimen from 2017 was examined using a genome-wide methylation analysis as well as a whole-genome sequencing. <b><i>Results:</i></b> These analyses confirmed the findings of 2002 and proved genetic alteration in the meningioma to be very stable over the time. Yet <i>SMO</i> and <i>AKT1</i> mutations, which have been described to be paradigmatic in frontobasal meningioma, could not be found. <b><i>Conclusions:</i></b> Genetic characteristics seem to be very stable during progression of the disease. The loss of 1p represents to be a potential marker for the poor clinical course of our child meningioma. In 2019, our patient passed away due to the progress of her meningioma disease.

Genome-wide association analysis in host characteristics of progression to high-grade cervical intraepithelial neoplasia for women with human papilloma virus infection and normal cytology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5109-5109
Author(s):  
Chyong-Huey Lai ◽  
Angel Chao ◽  
Chiao-Yun Lin ◽  
Chu-Chun Huang ◽  
Wen-Hui Su
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Membrane Trafficking ◽  
Intraepithelial Neoplasia ◽  
Genome Wide Association ◽  
Chromosome 17 ◽  
Normal Cytology ◽  
Genetic Characteristics ◽  
Genome Wide ◽  
A Genome

5109 Background: Although it is well accepted that persistent human papillomavirus (HPV) is necessary for carcinogenesis of cervical neoplasms, the molecular mechanism for progression is unclear. HPV testing is widely used for cervical cancer screening. The hazard ratio of developing cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) in baseline HPV-positive/normal cytology women is 30-50 fold as compared with HPV-negative/normal cytoloy women. HPV positivity would cause substantial anxiety. It is important to identify a prognostic profile for predicting progression. Methods: We collected blood samples from women aged ≥ 30 years in a population-based nested cohort study enrolling women with HPV infection (n = 871) or HPV-negative (n = 902) with normal cytology in 2004-2009 for prospective follow-up. To identify the host genetic characteristics associated with cervical carcinogenesis, a genome-wide association study (analyzing 530,194 SNPs) was conducted in 23 cases who developed CIN2+ and 62 viral type- and age-matched controls who were HPV-positive at baseline without developing CIN throughout the follow-up period. Results: One SNP with significant P values (rs16969682; P=4.58 x 10-5, OR=5.9, 95% CI=2.52-13.96) located in SEC14-like 1 (SEC14L1) gene localized to chromosome 17 was identified with association between progression to CIN2+ and controls without CIN throughout follow-up. SEC14L1 belongs to the widely-expressed SEC14-superfamily. This superfamily consists of > 500 members that are involved in biological functions including membrane trafficking and phospolipid metabolism. Furthermore, using T-cell based cDNA screening, SEC14L-1a is identified as a regulator of HIV-1 replication. Conclusions: The potential role of SEC14L1 in host-viral interaction will be further elucidated. Additional statistically significant SNPs including rs16969682 will be validated on cases with CIN2+ (n = 250) and normal controls (normal cytology/HPV-negative at baseline without acquisition of HPV or abnormal cytology/histology during follow-up, n = 500).

scholarly journals DNA Methylation at ATP11A cg11702988 Is a Biomarker of Lung Disease Severity in Cystic Fibrosis: A Longitudinal Study

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 441
Author(s):  
Fanny Pineau ◽  
Davide Caimmi ◽  
Sylvie Taviaux ◽  
Maurane Reveil ◽  
Laura Brosseau ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Dna Methylation ◽  
Clinical Trials ◽  
Lung Disease ◽  
Disease Severity ◽  
Genome Wide ◽  
A Genome ◽  
Lung Disease Severity ◽  
Epigenetic Biomarker

Cystic fibrosis (CF) is a chronic genetic disease that mainly affects the respiratory and gastrointestinal systems. No curative treatments are available, but the follow-up in specialized centers has greatly improved the patient life expectancy. Robust biomarkers are required to monitor the disease, guide treatments, stratify patients, and provide outcome measures in clinical trials. In the present study, we outline a strategy to select putative DNA methylation biomarkers of lung disease severity in cystic fibrosis patients. In the discovery step, we selected seven potential biomarkers using a genome-wide DNA methylation dataset that we generated in nasal epithelial samples from the MethylCF cohort. In the replication step, we assessed the same biomarkers using sputum cell samples from the MethylBiomark cohort. Of interest, DNA methylation at the cg11702988 site (ATP11A gene) positively correlated with lung function and BMI, and negatively correlated with lung disease severity, P. aeruginosa chronic infection, and the number of exacerbations. These results were replicated in prospective sputum samples collected at four time points within an 18-month period and longitudinally. To conclude, (i) we identified a DNA methylation biomarker that correlates with CF severity, (ii) we provided a method to easily assess this biomarker, and (iii) we carried out the first longitudinal analysis of DNA methylation in CF patients. This new epigenetic biomarker could be used to stratify CF patients in clinical trials.

scholarly journals Co-Overexpression of TWIST1-CSF1 Is a Common Event in Metastatic Oral Cancer and Drives Biologically Aggressive Phenotype

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 153
Author(s):  
Sabrina Daniela da Silva ◽  
Fabio Albuquerque Marchi ◽  
Jie Su ◽  
Long Yang ◽  
Ludmila Valverde ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Inflammatory Cells ◽  
Rank Test ◽  
Mesenchymal Transition ◽  
Genome Wide ◽  
A Genome ◽  
Enhanced Expression ◽  
Advanced Stages

Invasive oral squamous cell carcinoma (OSCC) is often ulcerated and heavily infiltrated by pro-inflammatory cells. We conducted a genome-wide profiling of tissues from OSCC patients (early versus advanced stages) with 10 years follow-up. Co-amplification and co-overexpression of TWIST1, a transcriptional activator of epithelial-mesenchymal-transition (EMT), and colony-stimulating factor-1 (CSF1), a major chemotactic agent for tumor-associated macrophages (TAMs), were observed in metastatic OSCC cases. The overexpression of these markers strongly predicted poor patient survival (log-rank test, p = 0.0035 and p = 0.0219). Protein analysis confirmed the enhanced expression of TWIST1 and CSF1 in metastatic tissues. In preclinical models using OSCC cell lines, macrophages, and an in vivo matrigel plug assay, we demonstrated that TWIST1 gene overexpression induces the activation of CSF1 while TWIST1 gene silencing down-regulates CSF1 preventing OSCC invasion. Furthermore, excessive macrophage activation and polarization was observed in co-culture system involving OSCC cells overexpressing TWIST1. In summary, this study provides insight into the cooperation between TWIST1 transcription factor and CSF1 to promote OSCC invasiveness and opens up the potential therapeutic utility of currently developed antibodies and small molecules targeting cancer-associated macrophages.

scholarly journals Methylome-wide analysis reveals epigenetic marks associated with resistance to tuberculosis in HIV-infected individuals from East Africa

2020 ◽  
Author(s):  
Catherine Stein ◽  
Penelope Bencheck ◽  
Jacquelaine Bartlett ◽  
Robert P Igo ◽  
Rafal S Sobota ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Sub Saharan Africa ◽  
Chromosome 1 ◽  
Chromosome 2 ◽  
Chromosome 5 ◽  
Epigenetic Marks ◽  
Genome Wide ◽  
A Genome ◽  
Immunodeficiency Virus ◽  
Sub Saharan

Background: Tuberculosis (TB) is the most deadly infectious disease globally and highly prevalent in the developing world, especially sub-Saharan Africa. Even though a third of humans are exposed to Myocbacterium tuberculosis (Mtb), most infected immunocompetent individuals do not develop active TB. In contrast, for individuals infected with both TB and the human immunodeficiency virus (HIV), the risk of active disease is 10% or more per year. Previously, we identified in a genome-wide association study a region on chromosome 5 that was associated with resistance to TB. This region included epigenetic marks that could influence gene regulation so we hypothesized that HIV-infected individuals exposed to Mtb, who remain disease free, carry epigenetic changes that strongly protect them from active TB. To test this hypothesis, we conducted a methylome-wide study in HIV-infected, TB-exposed cohorts from Uganda and Tanzania. Results: In 221 HIV-infected adults from Uganda and Tanzania, we identified 3 regions of interest that included markers that were differentially methylated between TB cases and LTBI controls, that also included methylation QTLs and associated SNPs: chromosome 1 (RNF220, p=4x10-5), chromosome 2 (between COPS8 and COL6A3 genes, p=2.7x10-5), and chromosome 5 (CEP72, p=1.3x10-5). These methylation results colocalized with associated SNPs, methylation QTLs, and methylation x SNP interaction effects. These markers were in regions with regulatory markers for cells involved in TB immunity and/or lung. Conclusion: Epigenetic regulation is a potential biologic factor underlying resistance to TB in immunocompromised individuals that can act in conjunction with genetic variants.

scholarly journals Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity

2021 ◽  
Author(s):  
Stefanie Andersson ◽  
Antonia Romero ◽  
Joana Isabel Rodrigues ◽  
Sansan Hua ◽  
Xinxin Hao ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Translational Control ◽  
Protein Biosynthesis ◽  
Cellular Systems ◽  
Genome Wide ◽  
A Genome ◽  
Toxic Metalloid ◽  
Arsenic Stress

The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells, and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified yeast deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis.

scholarly journals Each of 3,323 metabolic innovations in the evolution ofE. coliarose through the horizontal transfer of a single DNA segment

2018 ◽  
Vol 116 (1) ◽  
pp. 187-192 ◽  
Author(s):  
Tin Yau Pang ◽  
Martin J. Lercher
Keyword(s):  
E Coli ◽  
New Genes ◽  
Metabolic Adaptations ◽  
Genome Wide ◽  
A Genome ◽  
Individual Strain ◽  
History Of ◽  
Phenotype Space ◽  
Genome Content ◽  
Metabolic Models

Even closely related prokaryotes often show an astounding diversity in their ability to grow in different nutritional environments. It has been hypothesized that complex metabolic adaptations—those requiring the independent acquisition of multiple new genes—can evolve via selectively neutral intermediates. However, it is unclear whether this neutral exploration of phenotype space occurs in nature, or what fraction of metabolic adaptations is indeed complex. Here, we reconstruct metabolic models for the ancestors of a phylogeny of 53Escherichia colistrains, linking genotypes to phenotypes on a genome-wide, macroevolutionary scale. Based on the ancestral and extant metabolic models, we identify 3,323 phenotypic innovations in the history of theE. coliclade that arose through changes in accessory genome content. Of these innovations, 1,998 allow growth in previously inaccessible environments, while 1,325 increase biomass yield. Strikingly, every observed innovation arose through the horizontal acquisition of a single DNA segment less than 30 kb long. Although we found no evidence for the contribution of selectively neutral processes, 10.6% of metabolic innovations were facilitated by horizontal gene transfers on earlier phylogenetic branches, consistent with a stepwise adaptation to successive environments. Ninety-eight percent of metabolic phenotypes accessible to the combinedE. colipangenome can be bestowed on any individual strain by transferring a single DNA segment from one of the extant strains. These results demonstrate an amazing ability of theE. colilineage to adapt to novel environments through single horizontal gene transfers (followed by regulatory adaptations), an ability likely mirrored in other clades of generalist bacteria.

scholarly journals The Alkaline Phosphatase (ALPL) Locus Is Associated with B6 Vitamer Levels in CSF and Plasma

Genes ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 8 ◽  
Author(s):  
Loes Loohuis ◽  
Monique Albersen ◽  
Simone de Jong ◽  
Timothy Wu ◽  
Jurjen Luykx ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Genome Wide Association Study ◽  
Active Form ◽  
Minor Allele ◽  
Chromosome 1 ◽  
Joint Analysis ◽  
Genome Wide ◽  
A Genome

The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. The brain is dependent on vitamin B6 for its neurotransmitter balance. To obtain insight into the genetic determinants of vitamin B6 homeostasis, we conducted a genome-wide association study (GWAS) of the B6 vitamers pyridoxal (PL), PLP and the degradation product of vitamin B6, pyridoxic acid (PA). We collected a unique sample set of cerebrospinal fluid (CSF) and plasma from the same healthy human subjects of Dutch ancestry (n = 493) and included concentrations and ratios in and between these body fluids in our analysis. Based on a multivariate joint analysis of all B6 vitamers and their ratios, we identified a genome-wide significant association at a locus on chromosome 1 containing the ALPL (alkaline phosphatase) gene (minimal p = 7.89 × 10−10, rs1106357, minor allele frequency (MAF) = 0.46), previously associated with vitamin B6 levels in blood. Subjects homozygous for the minor allele showed a 1.4-times-higher ratio between PLP and PL in plasma, and even a 1.6-times-higher ratio between PLP and PL in CSF than subjects homozygous for the major allele. In addition, we observed a suggestive association with the CSF:plasma ratio of PLP on chromosome 15 (minimal p = 7.93 × 10−7, and MAF = 0.06 for rs28789220). Even though this finding is not reaching genome-wide significance, it highlights the potential of our experimental setup for studying transport and metabolism across the blood–CSF barrier. This GWAS of B6 vitamers identifies alkaline phosphatase as a key regulator in human vitamin B6 metabolism in CSF as well as plasma. Furthermore, our results demonstrate the potential of genetic studies of metabolites in plasma and CSF to elucidate biological aspects underlying metabolite generation, transport and degradation.

scholarly journals Molecular characteristics of Staphylococcus aureus associated prosthetic joint infections after hip fractures treated with hemiarthroplasty: a retrospective genome-wide association study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
J. Christopher Noone ◽  
Marc Stegger ◽  
Berit Lilje ◽  
Knut Stavem ◽  
Karin Helmersen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
University Hospital ◽  
Genome Wide Association ◽  
Molecular Characteristics ◽  
Joint Infections ◽  
Orthopaedic Patients ◽  
Prosthetic Joint ◽  
Genome Wide ◽  
A Genome ◽  
Prosthetic Joint Infections

Abstract A retrospective study of Staphylococcus aureus isolates from orthopaedic patients treated between 2000 and 2017 at Akershus University Hospital, Norway was performed using a genome-wide association approach. The aim was to characterize and investigate molecular characteristics unique to S. aureus isolates from HHA associated prosthetic joint infections and potentially explain the HHA patients’ elevated 1-year mortality compared to a non-HHA group. The comparison group consisted of patients with non-HHA lower-extremity implant-related S. aureus infections. S. aureus isolates from diagnostic patient samples were whole-genome sequenced. Univariate and multivariate analyses were performed to detect group-associated genetic signatures. A total of 62 HHA patients and 73 non-HHA patients were included. Median age (81 years vs. 74 years; p < 0.001) and 1-year mortality (44% vs. 15%, p < 0.001) were higher in the HHA group. A total of 20 clonal clusters (CCs) were identified; 75% of the isolates consisted of CC45, CC30, CC5, CC15, and CC1. Analyses of core and accessory genome content, including virulence, resistance genes, and k-mer analysis revealed few group-associated variants, none of which could explain the elevated 1-year mortality in HHA patients. Our findings support the premise that all S. aureus can cause invasive infections given the opportunity.

Detection of quantitative trait loci for locomotion and osteochondrosis-related traits in Large White ✕ Meishan pigs

2003 ◽  
Vol 76 (2) ◽  
pp. 155-165 ◽  
Author(s):  
G.J. Lee ◽  
A.L. Archibald ◽  
G.B. Garth ◽  
A.S. Law ◽  
D. Nicholson ◽  
...  
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Chromosome 1 ◽  
Chromosome 15 ◽  
Large White ◽  
Chromosome 13 ◽  
Genome Wide ◽  
A Genome ◽  
Trait Loci ◽  
Gait Score

AbstractData from the F2 generation of a Large White (LW) ✕ Meishan (MS) crossbred population were analysed to detect quantitative trait loci (QTL) for leg and gait scores, osteochondrosis and physis scores. Legs, feet and gait score were assessed in 308 F2 animals at 85 ( + 5) kg and osteochondrosis and physis scores were recorded for the right foreleg after slaughter. A genome scan was performed using 111 genetic markers chosen to span the genome that were genotyped on the F2 animals and their F1 parents and purebred grandparents. A QTL on chromosome 1 affecting gait score was significant at the genome-wide significance level. Additional QTL significant at the chromosome-wide 5% threshold level (approx. equivalent to the genome-wide suggestive level) were detected on chromosome 1 for front feet and back legs scores, on chromosome 13 for front legs and front feet scores, on chromosome 14 for front legs, front feet and back legs scores and on chromosome 15 for back feet score. None of the QTL for osteochondrosis score exceeded the chromosome-wide suggestive level, but one chromosome-wide QTL for physis score was found on chromosome 7. On chromosome 1, gait and front feet scores mapped to the middle of the chromosome and showed additive effects in favour of the LW alleles and no dominance effects. The QTL for back legs score mapped to the distal end of the chromosome and showed a dominant effect and no additive effect. On chromosomes 14 and 15, the LW allele was again superior to the MS allele. On chromosome 13, there were both additive and dominance effects in favour of the MS allele. The MS alleles on chromosome 13 may have potential for introgression into a commercial LW population. The other putative QTLs identified may have value in marker-assisted selection in LW or MS-synthetic populations.

Extended evidence for association between the melanoma inhibitory activity 3 gene and myocardial infarction

2011 ◽  
Vol 105 (04) ◽  
pp. 670-675 ◽  
Author(s):  
Anna Schatke ◽  
Hannah Wolferstetter ◽  
Jakob Mueller ◽  
Albert Schömig ◽  
Adnan Kastrati ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Inhibitory Activity ◽  
Chromosome 1 ◽  
Nucleotide Polymorphisms ◽  
Current Cigarette Smoking ◽  
A Genome ◽  
Increased Risk ◽  
Melanoma Inhibitory Activity ◽  
History Of ◽  
The Impact

SummaryIn a genome-wide scan, isolated single nucleotide polymorphisms (SNPs), including rs17465637, in the melanoma inhibitory activity 3 gene (MIA3) on chromosome 1 were identified to be associated with coronary artery disease and myocardial infarction (MI). Because the role of common variation at the MIA3 locus has not yet been investigated, the aim of this case-control study was to determine the impact of haplotype-tagging SNPs and haplotypes in the MIA3 region on the risk of MI. In a set of nine haplotype-tagging SNPs, rs17465637, but none of the other SNPs, was associated with MI. After adjustments were made for age, gender, history of arterial hypertension, history of hyper-cholesterolaemia, current cigarette smoking and diabetes mellitus, multiple logistic regression analyses showed an increased risk in the carriers of one or two C alleles [adjusted odds ratio (OR) 1.17, 95% confidence interval (CI) 1.04–1.32, and 1.37, 95% CI 1.08–1.74, respectively]. Nine common haplotypes (frequency >1%) were established across the MIA3 region. Two of the haplotypes were associated with an increased risk of MI: the frequent (48%) TGACCAAAG haplotype and the rare (2%) CGACCAAAG haplotype (adjusted OR 1.102, 95% CI 1.002–1.212, and 1.574, 95% CI 1.077–2.298, respectively). Showing association between rs17465637 and MI, this work was consistent with results from the original detection study and most prior replication studies addressing this issue. In addition to correspond with such isolated evidence of association with MI, the present study identified specific haplotypes capturing the risk-related variation in the entire MIA3 region.

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