scholarly journals Novel Genetic Rearrangements Termed “Structural Variation Polymorphisms“ Contribute to the Genetic Diversity of Orthohepadnaviruses

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 871
Author(s):  
Kei Fujiwara ◽  
Kentaro Matsuura ◽  
Kayoko Matsunami ◽  
Etsuko Iio ◽  
Yoshihito Nagura ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Structural Variation ◽  
Genomic Structure ◽  
Detailed Examination ◽  
Multiple Alignment ◽  
Structural Variations ◽  
Genetic Changes ◽  
Genetic Sequences ◽  
Genetic Rearrangements

The genetic diversity of orthohepadnaviruses is not yet fully understood. This study was conducted to investigate the role of structural variations (SVs) in their diversity. Genetic sequences of orthohepadnaviruses were retrieved from databases. The positions of sequence gaps were investigated, since they were found to be related to SVs, and they were further used to search for SVs. Then, a combination of pair-wise and multiple alignment analyses was performed to analyze the genomic structure. Unique patterns of SVs were observed; genetic sequences at certain genomic positions could be separated into multiple patterns, such as no SV, SV pattern 1, SV pattern 2, and SV pattern 3, which were observed as polymorphic changes. We provisionally referred to these genetic changes as SV polymorphisms. Our data showed that higher frequency of sequence gaps and lower genetic identity were observed in the pre-S1-S2 region of various types of HBVs. Detailed examination of the genetic structure in the pre-S region by a combination of pair-wise and multiple alignment analyses showed that the genetic diversity of orthohepadnaviruses in the pre-S1 region could have been also induced by SV polymorphisms. Our data showed that novel genetic rearrangements provisionally termed SV polymorphisms were observed in various orthohepadnaviruses.

scholarly journals A 6.5kb intergenic structural variation enhances P450-mediated resistance to pyrethroids in malaria vectors lowering bed net efficacy

2020 ◽  
Author(s):  
Leon M.J. Mugenzi ◽  
Benjamin D. Menze ◽  
Magellan Tchouakui ◽  
Murielle J. Wondji ◽  
Helen Irving ◽  
...  
Keyword(s):  
Structural Variation ◽  
Pyrethroid Resistance ◽  
Strong Association ◽  
Anopheles Funestus ◽  
Malaria Vectors ◽  
Structural Variations ◽  
Resistance Level ◽  
Translocation Event ◽  
Detrimental Impact

AbstractElucidating the complex evolutionary armory that mosquitoes deploy against insecticides is crucial to maintain the effectiveness of insecticide-based interventions. Here, we deciphered the role of a 6.5kb structural variation (SV) in driving cytochrome P450-mediated pyrethroid resistance in the malaria vector, Anopheles funestus. Whole genome pooled sequencing detected an intergenic 6.5kb SV between duplicated CYP6P9a/b P450s in pyrethroid resistant mosquitoes through a translocation event. Promoter analysis revealed a 17.5-fold higher activity (P<0.0001) for the SV-carrying fragment than the SV-free one. qRT-PCR expression profiling of CYP6P9a/b for each SV genotype supported its role as an enhancer since SV+/SV+ homozygote mosquitoes had significantly greater expression for both genes than heterozygotes SV+/SV- (1.7-2-fold) and homozygotes SV-/SV- (4-5-fold). Designing a PCR assay revealed a strong association between this SV and pyrethroid resistance (SV+/SV+ vs SV-/SV-; OR=2079.4, P=<0.001). The 6.5kb SV is present at high frequency in southern Africa (80-100%) but absent in East/Central/West Africa. Experimental hut trials revealed that homozygote SV mosquitoes had significantly greater chance to survive exposure to pyrethroid-treated Nets (OR 27.7; P < 0.0001) and to blood feed than susceptible. Furthermore, triple homozygote resistant (SV+/CYP6P9a_R/CYP6P9b_R) exhibit a higher resistance level leading to a far superior ability to survive exposure to nets than triple susceptible mosquitoes, revealing a strong additive effect. This study highlights the important role of structural variations in the development of insecticide resistance in malaria vectors and their detrimental impact on the effectiveness of pyrethroid-based nets.

The Interplay Between Secondhand Cigarette Smoke, Genetics, and Cervical Cancer: A Review of the Literature

2009 ◽  
Vol 10 (4) ◽  
pp. 392-399 ◽  
Author(s):  
Natalie Pate Capps ◽  
Ayasha Stewart ◽  
Cindy Burns
Keyword(s):  
Cervical Cancer ◽  
Cancer Risk ◽  
Genomic Structure ◽  
New Technology ◽  
Genetic Changes ◽  
Cervical Cancer Risk ◽  
Exposure Biomarkers ◽  
Shs Exposure ◽  
Pathologic Processes

Research has suggested a link between smoking and cervical cancer; however, little data are available on secondhand smoke (SHS) exposure and cervical cancer risk. This article reviews the literature on the links among smoking, SHS exposure and cervical cancer. The review was based on a search of electronic databases. The research reviewed clearly showed that smoking increases cervical cancer risk through myriad mechanisms that interact with genetics and the pathologic processes leading to cervical cancer. However, less is understood about the role of SHS in cervical cancer. With new technology enabling scientists to examine how genomic structure responds to environmental stimuli, more information should be forthcoming on links between SHS exposure, biomarkers, and genetic changes involved in the development of cervical cancer.

scholarly journals Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka
Keyword(s):  
Knee Osteoarthritis ◽  
Noncoding Rnas ◽  
Pathological Process ◽  
Joint Disease ◽  
Limited Information ◽  
Genetic Changes ◽  
Small Noncoding Rnas ◽  
Knee Oa ◽  
Cartilage Homeostasis

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.

First record of albino lowland tapirs (Tapirus terrestris Linnaeus 1758) in an important Brazilian Atlantic Forest hotspot

Mammalia ◽  
2020 ◽  
Vol 84 (6) ◽  
pp. 601-604
Author(s):  
Mariana Bueno Landis ◽  
Luciano Candisani ◽  
Leticia Prado Munhoes ◽  
João Carlos Zecchini Gebin ◽  
Frineia Rezende ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Atlantic Forest ◽  
Scientific Research ◽  
First Record ◽  
Brazilian Atlantic Forest ◽  
Tapirus Terrestris

AbstractAlbinism is the absence of pigmentation or coloration and is rarely found in nature. In this study we examined photos and videos obtained by cameras traps in the Legado das Águas Reserve. In the images, we identified two albino lowland tapirs. The results highlight the necessity of understanding the genetic diversity of lowland tapir populations and the important role of the professional photography associated with scientific research.

scholarly journals Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 593
Author(s):  
Srikanth Umakanthan ◽  
Maryann M Bukelo
Keyword(s):  
Epstein Barr Virus ◽  
Diagnostic Tools ◽  
Main Role ◽  
Genetic Changes ◽  
Barr Virus ◽  
Cancer Pathogenesis ◽  
Genomic Studies ◽  
Epstein Barr ◽  
Oncogenic Form

Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. This article reviews the role of genetic changes in EBV-associated lymphomas and carcinomas. This includes the prolific molecular genesis, key diagnostic tools, and target-specific drugs that have been in recent clinical use.

scholarly journals Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

2021 ◽  
Author(s):  
Wenhui Li ◽  
Wanjun Lei ◽  
Xiaopei Chao ◽  
Xiaochen Song ◽  
Yalan Bi ◽  
...  
Keyword(s):  
Copy Number ◽  
Somatic Mutations ◽  
Hpv Infection ◽  
Copy Number Variations ◽  
Cervical Adenocarcinoma ◽  
Structural Variations ◽  
Driver Genes ◽  
Genetic Changes ◽  
Genomic Changes ◽  
Whole Exome

AbstractThe association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

scholarly journals Dialectal intelligibility of Assamese tested functionally

2021 ◽  
Vol 2 (4) ◽  
pp. 9-22
Author(s):  
Sabbah Qamri
Keyword(s):  
Structural Variation ◽  
Native Speakers ◽  
Connected Speech ◽  
Regional Dialects ◽  
Testing Approach

This paper includes a detailed discussion on the intelligibility of the speakers of four regional dialects of the Indo-Aryan language of Assamese. Prior research on Assamese dialects mostly being confined to examining structural variation lends this study relevance and urgency. The dialects of Standard Assamese, Central Assamese, Kamrupi, and Goalparia, covering three varieties each, were considered for the study. Using a functional intelligibility testing approach, the rate of overall intelligibility as well as of inter- and intra-dialectal mutual intelligibility of the dialects were determined. 24 speakers (1 male and 1 female from each variety) were asked to record ‘texts’— words, sentences, and connected speech in their native varieties of Assamese. 11 listeners from each variety (132 in total) were then tested on their comprehension of texts from non-native varieties. Thereafter, their rates of comprehension were used to determine the rates of mutual intelligibility between speakers of the different dialects and varieties of Assamese. This paper establishes that the rates of mutual intelligibility are unequal and asymmetric among the dialects— the native speakers of the Standard and Central Assamese dialects were more intelligible to the speakers of Kamrupi and Goalparia than vice-versa. Finally, the paper finds that the rate of intelligibility is the lowest for words in isolation and reinforces the important role of context in intelligibility.

scholarly journals Ecological specialisation and evolutionary reticulation in extant Hyaenidae

2020 ◽  
Author(s):  
M V Westbury ◽  
Diana Le Duc ◽  
David A. Duchêne ◽  
Arunkumar Krishnan ◽  
Stefan Prost ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Single Species ◽  
Spotted Hyena ◽  
Genetic Changes ◽  
Slow Decline ◽  
Extant Species ◽  
Phylogenetic Discordance ◽  
Population Sizes ◽  
Olfactory Receptor Genes ◽  
Striped Hyena

AbstractDuring the Miocene, Hyaenidae was a highly diverse family of Carnivora that has since been severely reduced to four extant genera, each of which contains only a single species. These species include the bone-cracking spotted, striped, and brown hyenas, and the specialised insectivorous aardwolf. Previous genome studies have analysed the evolutionary histories of the spotted and brown hyenas, but little is known about the remaining two species. Moreover, the genomic underpinnings of scavenging and insectivory, defining traits of the extant species, remain elusive. To tackle these questions, we generated an aardwolf genome and analysed it together with those from the other three species. We provide new insights into the evolutionary relationships between the species, the genomic underpinnings of their scavenging and insectivorous lifestyles, and their respective genetic diversities and demographic histories. High levels of phylogenetic discordance within the family suggest gene flow between the aardwolf lineage and the ancestral brown/striped hyena lineage. Genes related to immunity and digestion in the bone-cracking hyenas and craniofacial development in the aardwolf showed the strongest signals of selection in their respective lineages, suggesting putative key adaptations to carrion or termite feeding. We also found a family-wide expansion in olfactory receptor genes suggesting that an acute sense of smell was a key early adaptation for the Hyaenidae family. Finally, we report very low levels of genetic diversity within the brown and striped hyenas despite no signs of inbreeding, which we putatively link to their similarly slow decline in Neover the last ∼2 million years. We found much higher levels of genetic diversity in both the spotted hyena and aardwolf and more stable population sizes through time. Taken together, these findings highlight how ecological specialisation can impact the evolutionary history, demographics, and adaptive genetic changes of a lineage.

scholarly journals Genetic diversity of Collaborative Cross mice controls viral replication, clinical severity and brain pathology induced by Zika virus infection, independently of Oas1b

2019 ◽  
Author(s):  
Caroline Manet ◽  
Etienne Simon-Lorière ◽  
Grégory Jouvion ◽  
David Hardy ◽  
Matthieu Prot ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Viral Load ◽  
Viral Replication ◽  
Clinical Severity ◽  
Brain Pathology ◽  
Zikv Infection ◽  
Infected Cells ◽  
Host Genetic ◽  
Host Genes

ABSTRACTThe explosive spread of Zika virus (ZIKV) has been associated with major variations in severe disease and congenital afflictions among infected populations, suggesting an influence of host genes. We investigated how genome-wide variants could impact susceptibility to ZIKV infection in mice. We first describe that the susceptibility of Ifnar1 knockout mice is largely influenced by their genetic background. We then show that the broad genetic diversity of Collaborative Cross mice, which receptor to type I interferon (IFNAR) was blocked by anti-IFNAR antibody, expressed phenotypes ranging from complete resistance to severe symptoms and death with large variations in the peak and rate of decrease of plasma viral load, in brain viral load, in brain histopathology and in viral replication rate in infected cells. Differences of susceptibility between CC strains were correlated between Zika, Dengue and West Nile viruses. We identified highly susceptible and resistant mouse strains as new models to investigate the mechanisms of human ZIKV disease and other flavivirus infections. Genetic analyses revealed that phenotypic variations are driven by multiple genes with small effects, reflecting the complexity of ZIKV disease susceptibility in human population. Notably, our results rule out a role of the Oas1b gene in the susceptibility to ZIKV. Altogether, this study emphasizes the role of host genes in the pathogeny of ZIKV infection and lays the foundation for further genetic and mechanistic studies.IMPORTANCEIn recent outbreaks, ZIKV has infected millions of people and induced rare but potentially severe complications, including Guillain-Barré syndrome and encephalitis in adults. While several viral sequence variants were proposed to enhance the pathogenicity of ZIKV, the influence of host genetic variants in the clinical heterogeneity remains mostly unexplored. We have addressed this question using a mouse panel which models the genetic diversity of human population and a ZIKV strain from a recent clinical isolate. Through a combination of in vitro and in vivo approaches, we demonstrate that multiple host genetic variants determine viral replication in infected cells, and clinical severity, kinetics of blood viral load and brain pathology in mice. We describe new mouse models expressing high susceptibility or resistance to ZIKV and to other flaviviruses. These models will facilitate the identification and mechanistic characterization of host genes that influence ZIKV pathogenesis.

scholarly journals Role of oncoviruses in oncogenesis

2020 ◽  
Vol 76 (12) ◽  
pp. 684-689
Author(s):  
Madej J.A.
Keyword(s):  
Growth Factors ◽  
Cell Growth ◽  
Neoplastic Transformation ◽  
Genetic Changes ◽  
Stimulate Cell Growth ◽  
Stimulate Cell ◽  
Optimization Principle ◽  
Clonal Development ◽  
Transcription Activators

The author describes DNA oncoviruses and RNA oncoviruses, their ways of infiltrating the host’s cells, and the possibilities of neoplastic transformation of cells by these microorganisms. The role of protooncogenesis and oncogenesis in both humans and animals is discussed. The transformation of cells by viruses is normally insufficient for oncogenesis; the cells also need to gain “immortality,” which usually requires 4-5 genetic changes (the so-called clonal development of cells), (Fig. 1). Oncoviruses remove suppressor growth factors while enhancing the effects that stimulate cell growth through e.g. hormones, cytokines, or transcription activators. In addition, the author discusses the role of the optimization principle in neogenesis.

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