scholarly journals Genome-wide mapping of genomic DNA damage: methods and implications

2021 ◽  
Author(s):  
Stefano Amente ◽  
Giovanni Scala ◽  
Barbara Majello ◽  
Somaiyeh Azmoun ◽  
Helen G. Tempest ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Dna ◽  
Positional Information ◽  
Cellular Function ◽  
Molecular Approaches ◽  
Genome Wide ◽  
Genomic Location ◽  
Mutational Hotspots ◽  
Genome Wide Data ◽  
The Impact

AbstractExposures from the external and internal environments lead to the modification of genomic DNA, which is implicated in the cause of numerous diseases, including cancer, cardiovascular, pulmonary and neurodegenerative diseases, together with ageing. However, the precise mechanism(s) linking the presence of damage, to impact upon cellular function and pathogenesis, is far from clear. Genomic location of specific forms of damage is likely to be highly informative in understanding this process, as the impact of downstream events (e.g. mutation, microsatellite instability, altered methylation and gene expression) on cellular function will be positional—events at key locations will have the greatest impact. However, until recently, methods for assessing DNA damage determined the totality of damage in the genomic location, with no positional information. The technique of “mapping DNA adductomics” describes the molecular approaches that map a variety of forms of DNA damage, to specific locations across the nuclear and mitochondrial genomes. We propose that integrated comparison of this information with other genome-wide data, such as mutational hotspots for specific genotoxins, tumour-specific mutation patterns and chromatin organisation and transcriptional activity in non-cancerous lesions (such as nevi), pre-cancerous conditions (such as polyps) and tumours, will improve our understanding of how environmental toxins lead to cancer. Adopting an analogous approach for non-cancer diseases, including the development of genome-wide assays for other cellular outcomes of DNA damage, will improve our understanding of the role of DNA damage in pathogenesis more generally.

scholarly journals Revealing the impact of the Caucasus region on the genetic legacy of Romani people from genome-wide data

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0202890 ◽  
Author(s):  
Zsolt Bánfai ◽  
Valerián Ádám ◽  
Etelka Pöstyéni ◽  
Gergely Büki ◽  
Márta Czakó ◽  
...  
Keyword(s):  
The Caucasus ◽  
Caucasus Region ◽  
Genome Wide ◽  
Genome Wide Data ◽  
The Impact

scholarly journals The impact of recent events on human genetic diversity

2012 ◽  
Vol 367 (1590) ◽  
pp. 793-799 ◽  
Author(s):  
Mark A. Jobling
Keyword(s):  
Genetic Diversity ◽  
Historical Record ◽  
Social Selection ◽  
New Methods ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Male Specific ◽  
Demographic Impact ◽  
The Impact ◽  
And Linguistics

The historical record tells us stories of migrations, population expansions and colonization events in the last few thousand years, but what was their demographic impact? Genetics can throw light on this issue, and has mostly done so through the maternally inherited mitochondrial DNA (mtDNA) and the male-specific Y chromosome. However, there are a number of problems, including marker ascertainment bias, possible influences of natural selection, and the obscuring layers of the palimpsest of historical and prehistorical events. Y-chromosomal lineages are particularly affected by genetic drift, which can be accentuated by recent social selection. A diversity of approaches to expansions in Europe is yielding insights into the histories of Phoenicians, Roma, Anglo-Saxons and Vikings, and new methods for producing and analysing genome-wide data hold much promise. The field would benefit from more consensus on appropriate methods, and better communication between geneticists and experts in other disciplines, such as history, archaeology and linguistics.

scholarly journals Pervasive selection biases inferences of the species tree

2020 ◽  
Author(s):  
Rui Borges ◽  
Bastien Boussau ◽  
Gergely Szollosi ◽  
Carolin Kosiol
Keyword(s):  
Simulated Data ◽  
Population Level ◽  
Fruit Fly ◽  
Genetic Distances ◽  
Species Tree ◽  
Molecular Dating ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Gc Bias ◽  
The Impact

Despite the importance of natural selection in species' evolutionary history, phylogenetic methods that take into account population-level processes ignore selection. Assuming neutrality is often based on the idea that selection occurs at a minority of loci in the genome and is unlikely to significantly compromise phylogenetic inferences. However, selection might behave more pervasively, as it the case of nearly neutral evolving mutations. Genome-wide processes like GC-bias and some of the variation segregating at the coding regions are known to evolve in the nearly neutral range. As we are now using genome-wide data to estimate species tree, it is just natural to ask whether weak, but pervasive, selection is likely to blur species tree inferences. Here, we employed a polymorphism-aware phylogenetic model, specially tailored for measuring signatures of nucleotide usage biases, to test the impact of nearly neutrally in the substitution process. Analyses with simulated data indicate that while the inferred relationships among species are not significantly compromised, the genetic distances are systematically underestimated, with the deeper nodes suffering more than the younger ones. Such biases have implications for molecular dating. We found signatures of GC-bias considerably affecting the estimated divergence times (up to 21%) of worldwide fruit fly populations. Our findings call for the need to account for nearly neutral forces (or any other form of pervasive selection) when quantifying divergence or dating species evolution.

scholarly journals In Silico Analysis of P450s and Their Role in Secondary Metabolism in the Bacterial Class Gammaproteobacteria

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1538
Author(s):  
Ntombizethu Nokuphiwa Msomi ◽  
Tiara Padayachee ◽  
Nomfundo Nzuza ◽  
Puleng Rosinah Syed ◽  
Justyna Dorota Kryś ◽  
...  
Keyword(s):  
Data Mining ◽  
Secondary Metabolism ◽  
Bacterial Species ◽  
In Silico Analysis ◽  
Cytochrome P450 Enzymes ◽  
Genome Data ◽  
Genome Wide ◽  
Genome Wide Data ◽  
The Impact ◽  
Silico Analysis

The impact of lifestyle on shaping the genome content of an organism is a well-known phenomenon and cytochrome P450 enzymes (CYPs/P450s), heme-thiolate proteins that are ubiquitously present in organisms, are no exception. Recent studies focusing on a few bacterial species such as Streptomyces, Mycobacterium, Cyanobacteria and Firmicutes revealed that the impact of lifestyle affected the P450 repertoire in these species. However, this phenomenon needs to be understood in other bacterial species. We therefore performed genome data mining, annotation, phylogenetic analysis of P450s and their role in secondary metabolism in the bacterial class Gammaproteobacteria. Genome-wide data mining for P450s in 1261 Gammaproteobacterial species belonging to 161 genera revealed that only 169 species belonging to 41 genera have P450s. A total of 277 P450s found in 169 species grouped into 84 P450 families and 105 P450 subfamilies, where 38 new P450 families were found. Only 18% of P450s were found to be involved in secondary metabolism in Gammaproteobacterial species, as observed in Firmicutes as well. The pathogenic or commensal lifestyle of Gammaproteobacterial species influences them to such an extent that they have the lowest number of P450s compared to other bacterial species, indicating the impact of lifestyle on shaping the P450 repertoire. This study is the first report on comprehensive analysis of P450s in Gammaproteobacteria.

scholarly journals Evaluating the Impact of Sex-Biased Genetic Admixture in the Americas through the Analysis of Haplotype Data

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1580
Author(s):  
Linda Ongaro ◽  
Ludovica Molinaro ◽  
Rodrigo Flores ◽  
Davide Marnetto ◽  
Marco R. Capodiferro ◽  
...  
Keyword(s):  
Social Practices ◽  
Genetic Admixture ◽  
X Chromosomes ◽  
Colonial Era ◽  
Post Colonial ◽  
Genome Wide ◽  
Haplotype Data ◽  
Genome Wide Data ◽  
Males And Females ◽  
The Impact

A general imbalance in the proportion of disembarked males and females in the Americas has been documented during the Trans-Atlantic Slave Trade and the Colonial Era and, although less prominent, more recently. This imbalance may have left a signature on the genomes of modern-day populations characterised by high levels of admixture. The analysis of the uniparental systems and the evaluation of continental proportion ratio of autosomal and X chromosomes revealed a general sex imbalance towards males for European and females for African and Indigenous American ancestries. However, the consistency and degree of this imbalance are variable, suggesting that other factors, such as cultural and social practices, may have played a role in shaping it. Moreover, very few investigations have evaluated the sex imbalance using haplotype data, containing more critical information than genotypes. Here, we analysed genome-wide data for more than 5000 admixed American individuals to assess the presence, direction and magnitude of sex-biased admixture in the Americas. For this purpose, we applied two haplotype-based approaches, ELAI and NNLS, and we compared them with a genotype-based method, ADMIXTURE. In doing so, besides a general agreement between methods, we unravelled that the post-colonial admixture dynamics show higher complexity than previously described.

scholarly journals Array-Based Comparative Genomic Hybridization Application for Revealing Genomic Micro Imbalances in Congenital Malformations

2009 ◽  
Vol 12 (1) ◽  
pp. 3-8
Author(s):  
S Hadjidekova ◽  
D Toncheva
Keyword(s):  
Comparative Genomic Hybridization ◽  
Congenital Malformations ◽  
Comparative Genomic ◽  
Whole Genome ◽  
Industrialized Countries ◽  
Genomic Hybridization ◽  
Genomic Imbalances ◽  
Genome Wide ◽  
Genomic Location ◽  
The Impact

Array-Based Comparative Genomic Hybridization Application for Revealing Genomic Micro Imbalances in Congenital MalformationsBirth defects affect 3-5% of live births and are a major cause of fetal, neonatal and infant morbidity and mortality in all industrialized countries. Some 40-60% of congenital physical anomalies in humans have no cause, 20% that seem to be multifactorial, 10-13% environmental and 12-25% genetic.Classical cytogenetic or common comparative genomic hybridization (CGH) methods have limited use in investigation of the whole genome because of their low resolution (5-10 Mb). Fluorescence in situ hybridization (FISH) and quantitative fluorescence polymerase chain reaction (QF-PCR) have higher resolution but do not allow genome-wide screening and require some prior knowledge regarding the suspected chromosomal abnormality and its genomic location.Because of these limitations, the impact of genetic micro imbalances as etiological factors for the development of congenital malformations (CM) is underestimated. Array-based techniques have enabled higher resolution screens for genomic imbalances in CM as they permit identification of micro aberrations with a size between 60 bp and several hundred kilobases. They make possible screening of the whole genome and detection of novel unbalanced micro structural rearrangements in a single reaction and also effective screening of new dose-dependent genes. In addition, the application of the aCGH technology has the potential to improve our understanding of the normal quantitative variants of the human genome.

scholarly journals Genetic Affinities among Southern Africa Hunter-Gatherers and the Impact of Admixing Farmer and Herder Populations

2019 ◽  
Vol 36 (9) ◽  
pp. 1849-1861 ◽  
Author(s):  
Mário Vicente ◽  
Mattias Jakobsson ◽  
Peter Ebbesen ◽  
Carina M Schlebusch
Keyword(s):  
Gene Flow ◽  
Southern Africa ◽  
Isolation By Distance ◽  
Hunter Gatherers ◽  
Data Set ◽  
Genome Wide ◽  
Distance Model ◽  
Comprehensive Picture ◽  
Genome Wide Data ◽  
The Impact

Abstract Southern African indigenous groups, traditionally hunter-gatherers (San) and herders (Khoekhoe), are commonly referred to as “Khoe-San” populations and have a long history in southern Africa. Their ancestors were largely isolated up until ∼2,000 years ago before the arrival of pastoralists and farmers in southern Africa. Assessing relationships among regional Khoe-San groups has been challenging due to admixture with immigrant populations that obscure past population affinities and gene flow among these autochthonous communities. We re-evaluate a combined genome-wide data set of previously published southern Africa Khoe-San populations in conjunction with novel data from Khoe-San individuals collected in Xade (Central Kalahari Game Reserve, Botswana) prior to their resettlement outside the reserve. After excluding regions in the genome that trace their ancestry to recent migrant groups, the genetic diversity of 20 Khoe-San groups fitted an isolation-by-distance model. Even though isolation-by-distance explained most genetic affinities between the different autochthonous groups, additional signals of contact between Khoe-San groups could be detected. For instance, we found stronger genetic affinities, than what would be explained by isolation-by-distance gene flow, between the two geographically separated Khoe-San groups, who speak branches of the Kx’a-language family (ǂHoan and Ju). We also scanned the genome-wide data for signals of adaptive gene flow from farmers/herders into Khoe-San groups and identified a number of genomic regions potentially introduced by the arrival of the new groups. This study provides a comprehensive picture of affinities among Khoe-San groups, prior to the arrival of recent migrants, and found that these affinities are primarily determined by the geographic landscape.

scholarly journals Genome-wide surveillance of transcription errors in response to genotoxic stress

2020 ◽  
Vol 118 (1) ◽  
pp. e2004077118
Author(s):  
C. Fritsch ◽  
J.-F. Gout ◽  
S. Haroon ◽  
A. Towheed ◽  
C. Chung ◽  
...  
Keyword(s):  
Dna Damage ◽  
Human Physiology ◽  
Genetic Instability ◽  
Genotoxic Stress ◽  
Genetic Mutations ◽  
Human Aging ◽  
Powerful Source ◽  
Genome Wide ◽  
The Impact ◽  
Kinetics Of

Mutagenic compounds are a potent source of human disease. By inducing genetic instability, they can accelerate the evolution of human cancers or lead to the development of genetically inherited diseases. Here, we show that in addition to genetic mutations, mutagens are also a powerful source of transcription errors. These errors arise in dividing and nondividing cells alike, affect every class of transcripts inside cells, and, in certain cases, greatly exceed the number of mutations that arise in the genome. In addition, we reveal the kinetics of transcription errors in response to mutagen exposure and find that DNA repair is required to mitigate transcriptional mutagenesis after exposure. Together, these observations have far-reaching consequences for our understanding of mutagenesis in human aging and disease, and suggest that the impact of DNA damage on human physiology has been greatly underestimated.

Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

2020 ◽  
Vol 23 ◽  
Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Silver Nanoparticles ◽  
Nuclear Dna ◽  
Liquid Paraffin ◽  
Tail Length ◽  
Hepatic Tissue ◽  
Tissue Destruction ◽  
Group 2 ◽  
The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

Sign in / Sign up

Export Citation Format

Share Document