The Needle in the Haystack—Searching for Genetic and Epigenetic Differences in Monozygotic Twins Discordant for Tetralogy of Fallot

Congenital heart defects (CHDs) are the most common birth defect in human with an incidence of almost 1% of all live births. Most cases have a multifactorial origin with both genetics and the environment playing a role in its development and progression. Adding an epigenetic component to this aspect is exemplified by monozygotic twins which share the same genetic background but have a different disease status. As a result, the interplay between the genetic, epigenetic and the environmental conditions might contribute to the etiology and phenotype. To date, the underlying causes of the majority of CHDs remain poorly understood. In this study, we performed genome-wide high-throughput sequencing to examine the genetic, structural genomic and epigenetic differences of two identical twin pairs discordant for Tetralogy of Fallot (TOF), representing the most common cyanotic form of CHDs. Our results show the almost identical genetic and structural genomic identity of the twins. In contrast, several epigenetic alterations could be observed given by DNA methylation changes in regulatory regions of known cardiac-relevant genes. Overall, this study provides first insights into the impact of genetic and especially epigenetic factors underlying monozygotic twins discordant for CHD like TOF.

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Assessing Genome-Wide Diversity in European Hantaviruses through Sequence Capture from Natural Host Samples

Viruses ◽

10.3390/v12070749 ◽

2020 ◽

Vol 12 (7) ◽

pp. 749 ◽

Cited By ~ 3

Author(s):

Melanie Hiltbrunner ◽

Gerald Heckel

Keyword(s):

High Throughput Sequencing ◽

De Novo ◽

Phylogenetic Analyses ◽

Common Vole ◽

Natural Host ◽

Sequence Information ◽

Coding Region ◽

Sequence Capture ◽

Genome Wide ◽

The Impact

Research on the ecology and evolution of viruses is often hampered by the limitation of sequence information to short parts of the genomes or single genomes derived from cultures. In this study, we use hybrid sequence capture enrichment in combination with high-throughput sequencing to provide efficient access to full genomes of European hantaviruses from rodent samples obtained in the field. We applied this methodology to Tula (TULV) and Puumala (PUUV) orthohantaviruses for which analyses from natural host samples are typically restricted to partial sequences of their tri-segmented RNA genome. We assembled a total of ten novel hantavirus genomes de novo with very high coverage (on average >99%) and sequencing depth (average >247×). A comparison with partial Sanger sequences indicated an accuracy of >99.9% for the assemblies. An analysis of two common vole (Microtus arvalis) samples infected with two TULV strains each allowed for the de novo assembly of all four TULV genomes. Combining the novel sequences with all available TULV and PUUV genomes revealed very similar patterns of sequence diversity along the genomes, except for remarkably higher diversity in the non-coding region of the S-segment in PUUV. The genomic distribution of polymorphisms in the coding sequence was similar between the species, but differed between the segments with the highest sequence divergence of 0.274 for the M-segment, 0.265 for the S-segment, and 0.248 for the L-segment (overall 0.258). Phylogenetic analyses showed the clustering of genome sequences consistent with their geographic distribution within each species. Genome-wide data yielded extremely high node support values, despite the impact of strong mutational saturation that is expected for hantavirus sequences obtained over large spatial distances. We conclude that genome sequencing based on capture enrichment protocols provides an efficient means for ecological and evolutionary investigations of hantaviruses at an unprecedented completeness and depth.

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Unbalanced Sample Size Introduces Spurious Correlations to Genome-wide Heterozygosity Analyses

10.1101/2020.02.06.937599 ◽

2020 ◽

Author(s):

Li Liu ◽

Richard J Caselli

Keyword(s):

Genetic Diversity ◽

Sample Size ◽

High Throughput Sequencing ◽

Rare Variants ◽

Meta Analysis ◽

Simulated Data ◽

Disease Status ◽

Future Research ◽

Data Sets ◽

Genome Wide

AbstractExcess of heterozygosity (H) is a widely used measure of genetic diversity of a population. As high-throughput sequencing and genotyping data become readily available, it has been applied to investigating the associations of genome-wide genetic diversity with human diseases and traits. However, these studies often report contradictory results. In this paper, we present a meta-analysis of five whole-exome studies to examine the association of H scores with Alzheimer’s disease. We show that the mean H score of a group is not associated with the disease status, but is associated with the sample size. Across all five studies, the group with more samples has a significantly lower H score than the group with fewer samples. To remove potential confounders in empirical data sets, we perform computer simulations to create artificial genomes controlled for the number of polymorphic loci, the sample size and the allele frequency. Analyses of these simulated data confirm the negative correlation between the sample size and the H score. Furthermore, we find that genomes with a large number of rare variants also have inflated H scores. These biases altogether can lead to spurious associations between genetic diversity and the phenotype of interest. Based on these findings, we advocate that studies shall balance the sample sizes when using genome-wide H scores to assess genetic diversities of different populations, which helps improve the reproducibility of future research.

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Faculty Opinions recommendation of The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14176957.15682057 ◽

2012 ◽

Author(s):

Anne Salonen

Keyword(s):

Gut Microbiome ◽

Monozygotic Twins ◽

Fermented Milk ◽

Gnotobiotic Mice ◽

The Impact

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Neuroblastoma and the epigenome

Cancer and Metastasis Reviews ◽

10.1007/s10555-020-09946-y ◽

2021 ◽

Author(s):

Irfete S. Fetahu ◽

Sabine Taschner-Mandl

Keyword(s):

Dna Methylation ◽

Histone Modifications ◽

Disease Diagnosis ◽

Dna Methyltransferases ◽

Epigenetic Alterations ◽

Aberrant Expression ◽

Tet Proteins ◽

Relative Paucity ◽

Underlying Causes ◽

Aberrant Dna Methylation

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.

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Growth and development of children under 5 years of age with tetralogy of Fallot in a Chinese population

Scientific Reports ◽

10.1038/s41598-021-93726-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xin Li ◽

Jin Zhu ◽

Jun An ◽

Yuqing Wang ◽

Yili Wu ◽

...

Keyword(s):

Body Weight ◽

Tetralogy Of Fallot ◽

Growth Retardation ◽

Growth And Development ◽

Heart Defects ◽

Body Height ◽

Child Growth ◽

The Body ◽

Early Age ◽

Local Conditions

AbstractCongenital Heart Defects (CHDs) are associated with different patterns of malnutrition and growth retardation, which may vary worldwide and need to be evaluated according to local conditions. Although tetralogy of Fallot (TOF) is one of the first described CHDs, the etiology outcomes in growth and development of TOF in early age child is still unclear in most cases. This study was designed to investigate the growth retardation status of Chinese pediatric TOF patients under 5 years old. The body height, body weight and body mass index (BMI) of 262 pediatric patients (138 boys and 124 girls) who underwent corrective surgery for TOF between 2014 and 2018 were measured using conventional methods. The average body height, body weight and BMI of the patients were significantly lower than WHO Child Growth Standards, while the most affected was body height. Meanwhile, higher stunting frequency and greater deterioration of both the body height and weight happened in elder age (aged 13–60 months) rather than in infant stage (aged 0–12 months) among these patients. Our results confirmed that intervention should be given at early age to prevent the growth retardation of TOF patients getting severer.

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An unusual case of tetralogy of Fallot with an absent pulmonary valve associated with a retro-aortic innominate vein in a patient with a 16p12.2 microdeletion

Cardiology in the Young ◽

10.1017/s1047951120004667 ◽

2021 ◽

pp. 1-2

Author(s):

Niall Linnane ◽

Andrew Green ◽

Colin J. McMahon

Keyword(s):

Aortic Arch ◽

Tetralogy Of Fallot ◽

Congenital Heart Defects ◽

Congenital Heart ◽

Unusual Case ◽

Pulmonary Valve ◽

Heart Defects ◽

Innominate Vein ◽

Absent Pulmonary Valve ◽

Rare Association

Abstract 16p12.2 microdeletion has been associated with congenital heart defects and developmental delay. In this case, we describe the rare association between tetralogy of Fallot with an absent pulmonary valve a right-sided aortic arch and a retro-aortic innominate vein associated with a 16p12.2 microdeletion and epilepsy.

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Chloroplast genome variation and phylogenetic relationships of Atractylodes species

BMC Genomics ◽

10.1186/s12864-021-07394-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yiheng Wang ◽

Sheng Wang ◽

Yanlei Liu ◽

Qingjun Yuan ◽

Jiahui Sun ◽

...

Keyword(s):

Chloroplast Genome ◽

High Throughput Sequencing ◽

Phylogenetic Analyses ◽

Herbal Medicines ◽

Structural Genomic ◽

Protein Coding ◽

Chloroplast Genomes ◽

Original Plant ◽

Morphological Differences ◽

Rna Genes

Abstract Background Atractylodes DC is the basic original plant of the widely used herbal medicines “Baizhu” and “Cangzhu” and an endemic genus in East Asia. Species within the genus have minor morphological differences, and the universal DNA barcodes cannot clearly distinguish the systemic relationship or identify the species of the genus. In order to solve these question, we sequenced the chloroplast genomes of all species of Atractylodes using high-throughput sequencing. Results The results indicate that the chloroplast genome of Atractylodes has a typical quadripartite structure and ranges from 152,294 bp (A. carlinoides) to 153,261 bp (A. macrocephala) in size. The genome of all species contains 113 genes, including 79 protein-coding genes, 30 transfer RNA genes and four ribosomal RNA genes. Four hotspots, rpl22-rps19-rpl2, psbM-trnD, trnR-trnT(GGU), and trnT(UGU)-trnL, and a total of 42–47 simple sequence repeats (SSR) were identified as the most promising potentially variable makers for species delimitation and population genetic studies. Phylogenetic analyses of the whole chloroplast genomes indicate that Atractylodes is a clade within the tribe Cynareae; Atractylodes species form a monophyly that clearly reflects the relationship within the genus. Conclusions Our study included investigations of the sequences and structural genomic variations, phylogenetics and mutation dynamics of Atractylodes chloroplast genomes and will facilitate future studies in population genetics, taxonomy and species identification.

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Persistent end-diastolic forward flow after pulmonary valve replacement in patients with repaired tetralogy of Fallot

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezab098 ◽

2021 ◽

Author(s):

Yuji Tominaga ◽

Masaki Taira ◽

Takashi Kido ◽

Tomomitsu Kanaya ◽

Kanta Araki ◽

...

Keyword(s):

Tetralogy Of Fallot ◽

Valve Replacement ◽

Pulmonary Valve ◽

Pulmonary Valve Replacement ◽

Right Atrial ◽

Volume Index ◽

Forward Flow ◽

Repaired Tetralogy Of Fallot ◽

Increased Risk ◽

The Impact

Abstract OBJECTIVES The clinical significance of persistent end-diastolic forward flow (EDFF) after pulmonary valve replacement (PVR) remains unclear in patients with repaired tetralogy of Fallot. This study aimed to identify the characteristics of these patients and the impact of persistent EDFF on outcomes. METHODS Of 46 consecutive patients who underwent PVR for moderate to severe pulmonary regurgitation between 2003 and 2019, 23 (50%) did not show EDFF before PVR [group (−)]. In the remaining 23 patients with EDFF before PVR, EDFF was diminished after PVR in 13 (28%) [group (+, −)] and persisted in 10 (22%) [group (+, +)]. The following variables were compared between these 3 groups: (i) preoperative right ventricular (RV) and right atrial volumes measured by magnetic resonance imaging, haemodynamic parameters measured by cardiac catheterization and the degree of RV myocardial fibrosis measured by RV biopsy obtained at PVR and (ii) the post-PVR course, development of atrial arrhythmia and need for intervention. RESULTS A high RV end-diastolic pressure, a greater right atrial volume index and a greater RV end-systolic volume index before PVR and a high degree of RV fibrosis were significantly associated with persistent EDFF 1 year after PVR. Persistent EDFF was a significant risk factor for postoperative atrial tachyarrhythmia, and catheter ablation and pacemaker implantation were required more frequently in these patients. CONCLUSIONS Persistent EDFF after PVR could predict a worse prognosis, especially an increased risk of arrhythmia. Close follow-up is required in patients with persistent EDFF for early detection of arrhythmia and prompt reintervention if necessary. Clinical trial registration number Institutional review board of Osaka University Hospital, number 16105

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Effects of pH shock on microaerobic activated sludge system with a graphene oxide/nano-magnetic powder composite

Nordic Pulp & Paper Research Journal ◽

10.1515/npprj-2020-0022 ◽

2020 ◽

Vol 35 (3) ◽

pp. 457-463

Author(s):

Huixia Lan ◽

Xiangzhi Wang ◽

Shixin Qi ◽

Da Yang ◽

Hao Zhang

Keyword(s):

Graphene Oxide ◽

Activated Sludge ◽

High Throughput Sequencing ◽

Impact Resistance ◽

Magnetic Powder ◽

Blank Group ◽

Activated Sludge System ◽

Ph Shock ◽

Dominant Bacteria ◽

The Impact

AbstractUsing the acclimated activated sludge from the pulping middle-stage effluent, the effect of pH shock on the micro-oxygen activated sludge system with a nano-magnetic powder/graphene oxide composite was studied. The results showed that the removal rates of chemical oxygen demand (CODCr) and ultraviolet adsorption at 254 nm (UV254) decreased. Also, the sludge settling performance was poor due to the impact of pH, but the impact resistance of nano-magnetic powder/graphene oxide group (MGO group) was higher and the recovery was faster. Results of high throughput sequencing indicated that the diversity of microbial community was reduced by the impact of pH, but it was significantly higher in MGO group than in the blank group. The dominant bacteria after pH shock or recovery in both of the system had a large difference. The percentage of the dominant bacteria in the MGO group was higher than that in the blank group. The MGO group had higher electron transfer system (ETS) activity which made the system having a strong pH impact resistance.

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