18,751 results on '"Genetic recombination"'
Search Results
2. The Third Codon Nucleotide’s Role in Genetic Recombination Within SARS-CoV-2 Spike Protein: A Pilot Study
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Guerrero-Tamayo, Ana, Urquijo, Borja Sanz, Olivares, Isabel, Tosantos, María-Dolores Moragues, Casado, Concepción, Pastor-López, Iker, Goos, Gerhard, Series Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Quintián, Héctor, editor, Corchado, Emilio, editor, Troncoso Lora, Alicia, editor, Pérez García, Hilde, editor, Jove Pérez, Esteban, editor, Calvo Rolle, José Luis, editor, Martínez de Pisón, Francisco Javier, editor, García Bringas, Pablo, editor, Martínez Álvarez, Francisco, editor, Herrero, Álvaro, editor, and Fosci, Paolo, editor
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- 2025
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3. Population Genomics of Adaptive Radiations: Exceptionally High Levels of Genetic Diversity and Recombination in an Endemic Spider From the Canary Islands.
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Escuer, Paula, Guirao‐Rico, Sara, Arnedo, Miquel A., Sánchez‐Gracia, Alejandro, and Rozas, Julio
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ADAPTIVE radiation , *ENDEMIC species , *SPECIES diversity , *GENETIC variation , *GENETIC recombination - Abstract
The spider genus Dysdera has undergone a remarkable diversification in the oceanic archipelago of the Canary Islands, with ~60 endemic species having originated during the 20 million years since the origin of the archipelago. This evolutionary radiation has been accompanied by substantial dietary shifts, often characterised by phenotypic modifications encompassing morphological, metabolic and behavioural changes. Hence, these endemic spiders represent an excellent model for understanding the evolutionary drivers and to pinpoint the genomic determinants underlying adaptive radiations. Recently, we achieved the first chromosome‐level genome assembly of one of the endemic species, D. silvatica, providing a high‐quality reference sequence for evolutionary genomics studies. Here, we conducted a low coverage‐based resequencing study of a natural population of D. silvatica from La Gomera island. Taking advantage of the new high‐quality genome, we characterised genome‐wide levels of nucleotide polymorphism, divergence and linkage disequilibrium, and inferred the demographic history of this population. We also performed comprehensive genome‐wide scans for recent positive selection. Our findings uncovered exceptionally high levels of nucleotide diversity and recombination in this geographically restricted endemic species, indicative of large historical effective population sizes. We also identified several candidate genomic regions that are potentially under positive selection, highlighting relevant biological processes, such as vision and nitrogen extraction as potential adaptation targets. These processes may ultimately drive species diversification in this genus. This pioneering study of spiders that are endemic to an oceanic archipelago lays the groundwork for broader population genomics analyses aimed at understanding the genetic mechanisms driving adaptive radiation in island ecosystems. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Understanding admixture fractions: theory and estimation of gene-flow.
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Liang, Mason, Shishkin, Mikhail, Shchur, Vladimir, and Nielsen, Rasmus
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AFRICAN American history , *GENETIC drift , *GENETIC models , *ESTIMATION theory , *GENETIC recombination - Abstract
Estimation of admixture proportions has become one of the most commonly used computational tools in population genomics. However, there is remarkably little population genetic theory on statistical properties of these variables. We develop theoretical results that can accurately predict means and variances of admixture proportions within a population using models with recombination and genetic drift. Based on established theory on measures of multilocus disequilibrium, we show that there is a set of recurrence relations that can be used to derive expectations for higher moments of the admixture proportions distribution. We obtain closed form solutions for some special cases. Using these results, we develop a method for estimating admixture parameters from estimated admixture proportions obtained from programs such as Structure or Admixture. We apply this method to HapMap 3 data and find that the population history of African Americans, as expected, is not best explained by a single admixture event between people of European and African ancestry. The model of constant gene flow starting at 8 generations and ending at 2 generations before present gives the best fit. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Genome-Wide Association Studies for Key Agronomic and Quality Traits in Potato (Solanum tuberosum L.).
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Yuan, Jianlong, Cheng, Lixiang, Wang, Yuping, and Zhang, Feng
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GENOME-wide association studies , *GENETIC recombination , *POTATO quality , *GENETIC mutation , *CHROMOSOMES - Abstract
Deciphering the genetic mechanisms underlying key agronomic and quality traits in potato (Solanum tuberosum L.) is essential for advancing varietal improvement. Phenotypic instability in early clonal generations and inbreeding depression, coupled with the complexity of tetrasomic inheritance, pose significant challenges in constructing mapping populations for the genetic dissection of complex traits. Genome-wide association studies (GWASs) offer an efficient method to establish trait–genome associations by analyzing genetic recombination and mutation events in natural populations. This review systematically examines the application of GWASs in identifying agronomic traits in potato, such as plant architecture, yield components, tuber shape, and resistance to early and late blight and nematodes, as well as quality traits including dry matter, starch, and glycoalkaloid content. Some key chromosomal hotspots identified through GWASs include chromosome 5 associated with tuber yield, starch content, and late blight resistance; chromosome 4 and 10 associations with tuber shape and starch content; chromosomes 1, 9, and 11 associated with plant height, tuber number, glycoalkaloid content, and pest resistance. It elucidates the advantages and limitations of GWASs for genetic loci identification in this autotetraploid crop, providing theoretical insights and a reference framework for the precise localization of key genetic loci and the discovery of underlying genes using GWASs. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Genomic analysis of an acute gastroenteritis outbreak caused by rotavirus C in Hebei, China.
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Wang, Kaiying, Wang, Yun, Yang, Lang, Li, Jinhui, Li, Peihan, Yang, Chaojie, Jia, Leili, Qiu, Shaofu, Song, Hongbin, and Li, Peng
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WHOLE genome sequencing , *GENETIC recombination , *GENETIC variation , *GENOMICS , *NUCLEOTIDE sequencing - Abstract
Rotavirus group C is an important cause of sporadic cases and outbreaks of gastroenteritis worldwide. Whole-Genome sequences of human rotavirus C (RVC) in public databases are limited. We performed genome sequencing to analyze a RVC outbreak of acute gastroenteritis in China. Samples from 22 patients were screened for pathogens using RT-PCR, and six samples were positive for rotavirus. Whole-Genome sequencing analysis showed that the outbreak strain SJZ217 belongs to the G4-P[2]-I2-R2-C2-M3-A2-N2-T2-E2-H2 genotype and shares almost identical genomic sequences with Chungnam isolated in Korea. Phylogenetic analysis revealed strain SJZ217 also fell into a cluster with rotavirus C strains from Japan and Europe. Reassortment in the VP4 fragment was observed. These results helped to understand the genetic diversity and possible spread of RVC strains. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Assisted sexual coral recruits show high thermal tolerance to the 2023 Caribbean mass bleaching event.
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Miller, Margaret W., Mendoza Quiroz, Sandra, Lachs, Liam, Banaszak, Anastazia T., Chamberland, Valérie F., Guest, James R., Gutting, Alexandra N., Latijnhouwers, Kelly R. W., Sellares-Blasco, Rita I., Virdis, Francesca, Villalpando, Maria F., and Petersen, Dirk
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MARINE heatwaves , *GENETIC recombination , *CORALS , *REPRODUCTIVE technology , *CORAL bleaching , *CORAL reefs & islands , *GENETIC variation - Abstract
Assisted sexual coral propagation, resulting in greater genet diversity via genetic recombination, has been hypothesized to lead to more adaptable and, hence, resilient restored populations compared to more common clonal techniques. Coral restoration efforts have resulted in substantial populations of 'Assisted sexual Recruits' (i.e., juvenile corals derived from assisted sexual reproduction; AR) of multiple species outplanted to reefs or held in in situ nurseries across many locations in the Caribbean. These AR populations provided context to evaluate their relative resilience compared to co-occurring coral populations during the 2023 marine heat wave of unprecedented duration and intensity that affected the entire Caribbean. Populations of six species of AR, most ranging in age from 1–4 years, were surveyed across five regions during the mass bleaching season in 2023 (Aug-Dec), alongside co-occurring groups of corals to compare prevalence of bleaching and related mortality. Comparison groups included conspecific adult colonies as available, but also the extant co-occurring coral assemblages in which conspecifics were rare or lacking, as well as small, propagated coral fragments. Assisted sexual recruits had significantly lower prevalence of bleaching impacts (overall pooled ~ 10%) than conspecific coral populations typically comprised of larger colonies (~ 60–100% depending on species). In addition, small corals derived from fragmentation (rather than sexual propagation) in two regions showed bleaching susceptibility intermediate between AR and wild adults. Overall, AR exhibited high bleaching resistance under heat stress exposure up to and exceeding Degree Heating Weeks of 20°C-weeks. As coral reefs throughout the globe are subject to increasingly frequent and intense marine heatwaves, restoration activities that include sexual reproduction and seeding can make an important contribution to sustain coral populations. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Alternative double strand break repair pathways shape the evolution of high recombination in the honey bee, Apis mellifera.
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Fouks, Bertrand, Miller, Katelyn J., Ross, Caitlin, Jones, Corbin, and Rueppell, Olav
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GENE conversion , *HOMOLOGOUS recombination , *HONEYBEES , *INSECT societies , *GENETIC recombination - Abstract
Social insects, particularly honey bees, have exceptionally high genomic frequencies of genetic recombination. This phenomenon and underlying mechanisms are poorly understood. To characterise the patterns of crossovers and gene conversion in the honey bee genome, a recombination map of 187 honey bee brothers was generated by whole‐genome resequencing. Recombination events were heterogeneously distributed without many true hotspots. The tract lengths between phase shifts were bimodally distributed, indicating distinct crossover and gene conversion events. While crossovers predominantly occurred in G/C‐rich regions and seemed to cause G/C enrichment, the gene conversions were found predominantly in A/T‐rich regions. The nucleotide composition of sequences involved in gene conversions that were associated with or distant from crossovers corresponded to the differences between crossovers and gene conversions. These combined results suggest two types of DNA double‐strand break repair during honey bee meiosis: non‐canonical homologous recombination, leading to gene conversion and A/T enrichment of the genome, and the canonical homologous recombination based on completed double Holliday Junctions, which can result in gene conversion or crossover and is associated with G/C bias. This G/C bias may be selected for to balance the A/T‐rich base composition of eusocial hymenopteran genomes. The lack of evidence for a preference of the canonical homologous recombination for double‐strand break repair suggests that the high genomic recombination rate of honey bees is mainly the consequence of a high rate of double‐strand breaks, which could in turn result from the life history of honey bees and their A/T‐rich genome. [ABSTRACT FROM AUTHOR]
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- 2024
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9. A Rapid Detection Method for H3 Avian Influenza Viruses Based on RT–RAA.
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Li, Jiaqi, Cui, Huan, Zhang, Yuxin, Wang, Xuejing, Liu, Huage, Mu, Yingli, Wang, Hongwei, Chen, Xiaolong, Dong, Tongchao, Zhang, Cheng, and Chen, Ligong
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AVIAN influenza A virus , *BLUE light , *GENETIC recombination , *GENETIC transcription , *POULTRY industry , *GENE amplification - Abstract
Simple Summary: The continuous evolution of the H3 subtype of avian influenza virus (AIV) poses a constant threat to the poultry industry and human health. This study successfully established a highly specific and rapid detection method for H3 AIV using real-time reverse transcription recombinase-aided isothermal amplification (RT–RAA). This method achieves accurate detection of H3 AIV by designing specific primers and probes without cross-reactivity with other viruses. The results show that the method exhibits high sensitivity and specificity and is highly consistent with the results of real-time quantitative PCR (RT–qPCR). In addition, RT–RAA amplification products can be visually observed by a portable blue light instrument, which is suitable for rapid detection in resource-constrained settings. The continued evolution of H3 subtype avian influenza virus (AIV)—which crosses the interspecific barrier to infect humans—and the potential risk of genetic recombination with other subtypes pose serious threats to the poultry industry and human health. Therefore, rapid and accurate detection of H3 virus is highly important for preventing its spread. In this study, a method based on real-time reverse transcription recombinase-aided isothermal amplification (RT–RAA) was successfully developed for the rapid detection of H3 AIV. Specific primers and probes were designed to target the hemagglutinin (HA) gene of H3 AIV, ensuring highly specific detection of H3 AIV without cross-reactivity with other important avian respiratory viruses. The results showed that the detection limit of the RT–RAA fluorescence reading method was 224 copies/response within the 95% confidence interval, while the detection limit of the RT–RAA visualization method was 1527 copies/response within the same confidence interval. In addition, 68 clinical samples were examined and the results were compared with those of real-time quantitative PCR (RT–qPCR). The results showed that the real-time fluorescence RT–RAA and RT–qPCR results were completely consistent, and the kappa value reached 1, indicating excellent correlation. For visual detection, the sensitivity was 91.43%, the specificity was 100%, and the kappa value was 0.91, which also indicated good correlation. In addition, the amplified products of RT–RAA can be visualized with a portable blue light instrument, which enables rapid detection of H3 AIV even in resource-constrained environments. The H3 AIV RT-RAA rapid detection method established in this study can meet the requirements of basic laboratories and provide a valuable reference for the early diagnosis of H3 AIV. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Rabbit hemorrhagic disease virus 2, 2010–2023: a review of global detections and affected species.
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Asin, Javier, Calvete, Carlos, Uzal, Francisco A., Crossley, Beate M., Duarte, Margarida Dias, Henderson, Eileen E., and Abade dos Santos, Fábio
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RABBIT diseases ,EUROPEAN rabbit ,DISSEMINATED intravascular coagulation ,GENETIC recombination ,RED beds - Abstract
Rabbit hemorrhagic disease virus 2/genotype GI.2 (RHDV2/GI.2; Caliciviridae, Lagovirus) causes a highly contagious disease with hepatic necrosis and disseminated intravascular coagulation in several Leporidae species. RHDV2 was first detected in European rabbits (Oryctolagus cuniculus) in France in 2010 and has since spread widely. We gather here data on viral detections reported in various countries and affected species, and discuss pathology, genetic differences, and novel diagnostic aspects. RHDV2 has been detected almost globally, with cases reported in Europe, Africa, Oceania, Asia, and North America as of 2023. Since 2020, large scale outbreaks have occurred in the United States and Mexico and, at the same time, cases have been reported for the first time in previously unaffected countries, such as China, Japan, Singapore, and South Africa, among others. Detections have been notified in domestic and wild European rabbits, hares and jackrabbits (Lepus spp.), several species of cottontail and brush rabbits (Sylvilagus spp.), pygmy rabbits (Brachylagus idahoensis), and red rock rabbits (Pronolagus spp.). RHDV2 has also been detected in a few non-lagomorph species. Detection of RHDV2 causing RHD in Sylvilagus spp. and Leporidae species other than those in the genera Oryctolagus and Lepus is very novel. The global spread of this fast-evolving RNA virus into previously unexploited geographic areas increases the likelihood of host range expansion as new species are exposed; animals may also be infected by nonpathogenic caliciviruses that are disseminated by almost all species, and with which genetic recombination may occur. [ABSTRACT FROM AUTHOR]
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- 2024
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11. The Genetic Architecture of Recombination Rates is Polygenic and Differs Between the Sexes in Wild House Sparrows (Passer domesticus).
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McAuley, John B, Servin, Bertrand, Burnett, Hamish A, Brekke, Cathrine, Peters, Lucy, Hagen, Ingerid J, Niskanen, Alina K, Ringsby, Thor Harald, Husby, Arild, Jensen, Henrik, and Johnston, Susan E
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QUANTITATIVE genetics ,GENETIC correlations ,ENGLISH sparrow ,GENETIC recombination ,GENETIC variation - Abstract
Meiotic recombination through chromosomal crossing-over is a fundamental feature of sex and an important driver of genomic diversity. It ensures proper disjunction, allows increased selection responses, and prevents mutation accumulation; however, it is also mutagenic and can break up favorable haplotypes. This cost–benefit dynamic is likely to vary depending on mechanistic and evolutionary contexts, and indeed, recombination rates show huge variation in nature. Identifying the genetic architecture of this variation is key to understanding its causes and consequences. Here, we investigate individual recombination rate variation in wild house sparrows (Passer domesticus). We integrate genomic and pedigree data to identify autosomal crossover counts (ACCs) and intrachromosomal allelic shuffling ( r ¯ i n t r a ) in 13,056 gametes transmitted from 2,653 individuals to their offspring. Females had 1.37 times higher ACC, and 1.55 times higher r ¯ i n t r a than males. ACC and r ¯ i n t r a were heritable in females and males (ACC h
2 = 0.23 and 0.11; r ¯ i n t r a h2 = 0.12 and 0.14), but cross-sex additive genetic correlations were low (rA = 0.29 and 0.32 for ACC and r ¯ i n t r a ). Conditional bivariate analyses showed that all measures remained heritable after accounting for genetic values in the opposite sex, indicating that sex-specific ACC and r ¯ i n t r a can evolve somewhat independently. Genome-wide models showed that ACC and r ¯ i n t r a are polygenic and driven by many small-effect loci, many of which are likely to act in trans as global recombination modifiers. Our findings show that recombination rates of females and males can have different evolutionary potential in wild birds, providing a compelling mechanism for the evolution of sexual dimorphism in recombination. [ABSTRACT FROM AUTHOR]- Published
- 2024
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12. Annelid Comparative Genomics and the Evolution of Massive Lineage-Specific Genome Rearrangement in Bilaterians.
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Lewin, Thomas D, Liao, Isabel Jiah-Yih, and Luo, Yi-Jyun
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SYMMETRY (Biology) ,GENETIC recombination ,COMPARATIVE genomics ,CHROMOSOMES ,CLITELLATA - Abstract
The organization of genomes into chromosomes is critical for processes such as genetic recombination, environmental adaptation, and speciation. All animals with bilateral symmetry inherited a genome structure from their last common ancestor that has been highly conserved in some taxa but seemingly unconstrained in others. However, the evolutionary forces driving these differences and the processes by which they emerge have remained largely uncharacterized. Here, we analyze genome organization across the phylum Annelida using 23 chromosome-level annelid genomes. We find that while many annelid lineages have maintained the conserved bilaterian genome structure, the Clitellata, a group containing leeches and earthworms, possesses completely scrambled genomes. We develop a rearrangement index to quantify the extent of genome structure evolution and show that, compared to the last common ancestor of bilaterians, leeches and earthworms have among the most highly rearranged genomes of any currently sampled species. We further show that bilaterian genomes can be classified into two distinct categories—high and low rearrangement—largely influenced by the presence or absence, respectively, of chromosome fission events. Our findings demonstrate that animal genome structure can be highly variable within a phylum and reveal that genome rearrangement can occur both in a gradual, stepwise fashion, or rapid, all-encompassing changes over short evolutionary timescales. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Genomic analysis of an acute gastroenteritis outbreak caused by rotavirus C in Hebei, China
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Kaiying Wang, Yun Wang, Lang Yang, Jinhui Li, Peihan Li, Chaojie Yang, Leili Jia, Shaofu Qiu, Hongbin Song, and Peng Li
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Human rotavirus C ,Phylogenetic analysis ,Genetic recombination ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Rotavirus group C is an important cause of sporadic cases and outbreaks of gastroenteritis worldwide. Whole-Genome sequences of human rotavirus C (RVC) in public databases are limited. We performed genome sequencing to analyze a RVC outbreak of acute gastroenteritis in China. Samples from 22 patients were screened for pathogens using RT-PCR, and six samples were positive for rotavirus. Whole-Genome sequencing analysis showed that the outbreak strain SJZ217 belongs to the G4-P[2]-I2-R2-C2-M3-A2-N2-T2-E2-H2 genotype and shares almost identical genomic sequences with Chungnam isolated in Korea. Phylogenetic analysis revealed strain SJZ217 also fell into a cluster with rotavirus C strains from Japan and Europe. Reassortment in the VP4 fragment was observed. These results helped to understand the genetic diversity and possible spread of RVC strains.
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- 2024
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14. REC protein family expansion by the emergence of a new signaling pathway.
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Garber, Megan, Frank, Vered, Kazakov, Alexey, Incha, Matthew, Nava, Alberto, Zhang, Hanqiao, Valencia, Luis, Keasling, Jay, Rajeev, Lara, and Mukhopadhyay, Aindrila
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domain swapping ,evolution ,gene regulation ,genetic recombination ,large protein families ,response regulator ,signal transduction ,two-component regulatory systems - Abstract
We explore when and why large classes of proteins expand into new sequence space. We used an unsupervised machine learning approach to observe the sequence landscape of REC domains of bacterial response regulator proteins. We find that within-gene recombination can switch effector domains and, consequently, change the regulatory context of the duplicated protein.
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- 2023
15. An efficient gene targeting system using Δku80 and functional analysis of Cyp51A in Trichophyton rubrum.
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Ishii, Masaki, Yamada, Tsuyoshi, and Ohata, Shinya
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GENE targeting , *GENE expression , *DRUG tolerance , *GENETIC recombination , *DRUG resistance - Abstract
Trichophyton rubrum is one of the most frequently isolated fungi in patients with dermatophytosis. Despite its clinical significance, the molecular mechanisms of drug resistance and pathogenicity of T. rubrum remain to be elucidated because of the lack of genetic tools, such as efficient gene targeting systems. In this study, we generated a T. rubrum strain that lacks the nonhomologous end-joining-related gene ku80 (Δku80) and then developed a highly efficient genetic recombination system with gene targeting efficiency that was 46 times higher than that using the wild-type strain. Cyp51A and Cyp51B are 14-α-lanosterol demethylase isozymes in T. rubrum that promote ergosterol biosynthesis and are the targets of azole antifungal drugs. The expression of cyp51A mRNA was induced by the addition of the azole antifungal drug efinaconazole, whereas no such induction was detected for cyp51B, suggesting that Cyp51A functions as an azole-responsive Cyp51 isozyme. To explore the contribution of Cyp51A to susceptibility to azole drugs, the neomycin phosphotransferase (nptII) gene cassette was inserted into the cyp51A 3′-untranslated region of Δku80 to destabilize the mRNA of cyp51A. In this mutant, the induction of cyp51A mRNA expression by efinaconazole was diminished. The minimum inhibitory concentration for several azole drugs of this strain was reduced, suggesting that dermatophyte Cyp51A contributes to the tolerance for azole drugs. These findings suggest that an efficient gene targeting system using Δku80 in T. rubrum is applicable for analyzing genes encoding drug targets. Key Points: A novel gene targeting system using Δku80 strain was established in T. rubrum Cyp51A in T. rubrum responds to the azole antifungal drug efinaconazole Cyp51A contributes to azole drug tolerance in T. rubrum [ABSTRACT FROM AUTHOR]
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- 2024
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16. Genetic variation and recombination analysis of PRRSV-2 GP3 gene in China from 1996 to 2023.
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Chen Lv, Yajie Zheng, Kexin Liu, Gan Li, Qin Luo, Hang Zhang, Huiyang Sha, Ruining Wang, Weili Kong, and Mengmeng Zhao
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GENETIC recombination ,AMINO acid sequence ,GENETIC variation ,GENE families ,SWINE industry ,PORCINE reproductive & respiratory syndrome - Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) has become widespread in China particularly the highly pathogenic porcine reproductive and respiratory syndromes (HP-PRRSV), NADC30, and NADC34 strains, and has posed a threat to the swine industry for over 20 years. To monitor genetic variation in PRRSV-2 GP3 strains in China, we analyzed 618 strains isolated between 1996 to 2023 and constructed phylogenetic trees. Additionally, 60 selected strains were used to analyze nucleotide and amino acid homology. PRRSV GP3 gene exhibited nucleotide identity ranging from 78.2% to 100.0% and amino acid similarity ranging from 74.9% to 99.6%. The GP3 gene in the 60 selected strains consisted of 254 amino acids, and amino acid mutations in the strains primarily occurred in B-cell epitopes, T-cell epitopes, and highly variable regions. The glycosylation sites of the strains used for amino acid sequence comparisons remained unaltered, except for the N
29 site in the GD20220303-2022 strain. PRRSV-2 strains in China belong to lineages 1, 3, 5, and 8. Recombination analysis detected two recombination events, involving lineages 1 and 8. In conclusion, this study investigated multiple strains of the PRRSV-2 GP3 gene to explore the prevalence and genetic diversity of the GP3 gene in China from a gene family perspective. The results of the analyses provide a basis for clinical prevention strategies and vaccine development. [ABSTRACT FROM AUTHOR]- Published
- 2024
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17. refMLST: reference-based multilocus sequence typing enables universal bacterial typing.
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Khdhiri, Mondher, Thomas, Ella, de Smet, Chanel, Chandar, Priyanka, Chandrakumar, Induja, Davidson, Jean M., Anderson, Paul, and Chorlton, Samuel D.
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GENETIC recombination , *YERSINIA enterocolitica , *BACTERIAL typing , *SINGLE nucleotide polymorphisms , *GENOMES - Abstract
Background: Commonly used approaches for genomic investigation of bacterial outbreaks, including SNP and gene-by-gene approaches, are limited by the requirement for background genomes and curated allele schemes, respectively. As a result, they only work on a select subset of known organisms, and fail on novel or less studied pathogens. We introduce refMLST, a gene-by-gene approach using the reference genome of a bacterium to form a scalable, reproducible and robust method to perform outbreak investigation. Results: When applied to multiple outbreak causing bacteria including 1263 Salmonella enterica, 331 Yersinia enterocolitica and 6526 Campylobacter jejuni genomes, refMLST enabled consistent clustering, improved resolution, and faster processing in comparison to commonly used tools like chewieSnake. Conclusions: refMLST is a novel multilocus sequence typing approach that is applicable to any bacterial species with a public reference genome, does not require a curated scheme, and automatically accounts for genetic recombination. Availability and implementation: refMLST is freely available for academic use at https://bugseq.com/academic. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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18. Classification of SARS-CoV-2 sequences as recombinants via a pre-trained CNN and identification of a mathematical signature relative to recombinant feature at Spike, via interpretability.
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Guerrero-Tamayo, Ana, Sanz Urquijo, Borja, Olivares, Isabel, Moragues Tosantos, María-Dolores, Casado, Concepción, and Pastor-López, Iker
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GENETIC recombination , *ARITHMETIC series , *COVID-19 pandemic , *IMAGE processing , *SARS-CoV-2 , *SPECTROGRAMS - Abstract
The global impact of the SARS-CoV-2 pandemic has underscored the need for a deeper understanding of viral evolution to anticipate new viruses or variants. Genetic recombination is a fundamental mechanism in viral evolution, yet it remains poorly understood. In this study, we conducted a comprehensive research on the genetic regions associated with genetic recombination features in SARS-CoV-2. With this aim, we implemented a two-phase transfer learning approach using genomic spectrograms of complete SARS-CoV-2 sequences. In the first phase, we utilized a pre-trained VGG-16 model with genomic spectrograms of HIV-1, and in the second phase, we applied HIV-1 VGG-16 model to SARS-CoV-2 spectrograms. The identification of key recombination hot zones was achieved using the Grad-CAM interpretability tool, and the results were analyzed by mathematical and image processing techniques. Our findings unequivocally identify the SARS-CoV-2 Spike protein (S protein) as the pivotal region in the genetic recombination feature. For non-recombinant sequences, the relevant frequencies clustered around 1/6 and 1/12. In recombinant sequences, the sharp prominence of the main hot zone in the Spike protein prominently indicated a frequency of 1/6. These findings suggest that in the arithmetic series, every 6 nucleotides (two triplets) in S may encode crucial information, potentially concealing essential details about viral characteristics, in this case, recombinant feature of a SARS-CoV-2 genetic sequence. This insight further underscores the potential presence of multifaceted information within the genome, including mathematical signatures that define an organism's unique attributes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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19. Using preimplantation genetic testing for monogenic disease for preventing citrullinemia type 1 transmission.
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Zubo Wu, Tao Liang, Yi Liu, Xiaofang Ding, and Defeng Shu
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GENETIC testing ,MEDICAL genetics ,GENETIC variation ,HAPLOTYPES ,GENETIC recombination - Abstract
Aim: The aimof this study is to investigate if Preimplantation Genetic Testing (PGT) can effectively identify unreported variants according to American College of Medical Genetics and Genomics (ACMG)to prevent citrullinemia type 1 affection. Design: This study involves a detailed case analysis of a family with history of citrullinemia type 1, focusing on the use of PGT for monogenic diseases (PGT-M). The genetic variants were identified using ACMG guidelines, and PGT was employed to prevent the inheritance of these variants. The study included haplotype analysis and Sanger sequencing to confirm the results. Results: The study identified previously unreported variations in the ASS1 gene causing citrullinemia type 1. PGT successfully prevented the transmission of these variants, resulting in the birth of a healthy fetus. However, challenges such as allele dropout (ADO) and gene recombination were encountered during haplotype analysis, which could potentially defeat the diagnosis. The study demonstrated that combining haplotype analysis with Sanger sequencing can enhance the accuracy of PGT. Conclusion: Preimplantation Genetic Testing (PGT) targeting likely pathogenic and pathogenic variants in the ASS1 gene, as rated by ACMG, allows the birth of healthy infants free from citrullinemia type 1. Additionally, the establishment of single haplotypes and Sanger sequencing can reduce the misdiagnosis rate caused by allele dropout (ADO) and genetic recombination. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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20. Genetic variation and recombination analysis of the GP5 gene of the porcine reproductive and respiratory syndrome virus in Thailand.
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Yajie Zheng, Gan Li, Kexin Liu, Qin Luo, Wenchao Sun, and Mengmeng Zhao
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GENETIC recombination ,PORCINE reproductive & respiratory syndrome ,GENETIC variation ,CIRCOVIRUS diseases ,AMINO acid sequence ,SWINE industry ,SEQUENCE alignment - Abstract
Introduction: Porcine reproductive and respiratory syndrome (PRRS) is a significant threat to the global swine industry, and its prevalence in Thailand spans over two decades. Methods: To understand the genetic variation and recombination of the PRRS virus (PRRSV) GP5 gene in Thailand, we retrieved 726 GP5 gene sequences from the NCBI database. Phylogenetic trees were constructed using the neighbor-joining (NJ) and maximum likelihood (ML) methods, and recombination analysis was performed. Results: Homology analysis was conducted on 83 PRRSV-1 and 83 PRRSV-2 strains. Phylogenetic analysis revealed the prevalence of both PRRSV-1 and PRRSV-2 strains in Thailand, with the latter exhibiting wider distribution. PRRSV-1 strains clustered into clades A, D, and H, while PRRSV-2 strains grouped into lineages 1, 5, and sublineage 8.7, further divided into 8.7/HP and 8.7/NA sublineages. Sublineage 8.7/NA strains accounted for a significant proportion of circulating PRRSV-2 strains. Homology analysis showed nucleotide and amino acid similarities ranging from 75.4 to 100.0% and 41.3 to 100.0% for PRRSV-1, and 78.6 to 100.0% and 70.8 to 100.0% for PRRSV-2 strains. Amino acid sequence alignments revealed mutations, insertions, and deletions in PRRSV-1 GP5, and key residue mutations in PRRSV-2 GP5 associated with biological functions. Recombination analysis identified two recombination events within PRRSV-2 sublineage 8.7 strains. Discussion: These findings confirm the variability of the GP5 protein. This study enhances our understanding of PRRSV prevalence and genetic variation in Thailand, contributing valuable insights for PRRS prevention and control. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Intra- and inter-host origin, evolution dynamics and spatial-temporal transmission characteristics of circoviruses.
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Yongqiu Cui, Siting Li, Weiying Xu, Jiali Xie, Dedong Wang, Lei Hou, Jianwei Zhou, Xufei Feng, and Jue Liu
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GENETIC recombination ,CIRCOVIRUSES ,RANDOM variables ,ANIMAL species ,ANIMAL diseases ,CIRCOVIRUS diseases - Abstract
Introduction: Since their identification in 1974, circoviruses have caused clinicopathological diseases in various animal species, including humans. However, their origin, transmission, and genetic evolution remain poorly understood. Methods: In this study, the genome sequences of circovirus were obtained from GenBank, and the Bayesian stochastic search variable selection algorithm was employed to analyzed the evolution and origin of circovirus. Results: Here, the evolutionary origin, mode of transmission, and genetic recombination of the circovirus were determined based on the available circovirus genome sequences. The origin of circoviruses can be traced back to fish circovirus, which might derive from fish genome, and human contributes to transmission of fish circovirus to other species. Furthermore, mosquitos, ticks, bats, and/or rodents might play a role as intermediate hosts in circovirus intraand inter-species transmission. Two major lineages (A and B) of circoviruses are identified, and frequent recombination events accelerate their variation and spread. The time to the most recent common ancestor of circoviruses can be traced back to around A.D. 600 and has been evolving at a rate of 10
-4 substitutions site-1 year-1 for a long time. Discussion: These comprehensive findings shed light on the evolutionary origin, population dynamics, transmission model, and genetic recombination of the circovirus providing valuable insights for the development of prevention and control strategies against circovirus infections. [ABSTRACT FROM AUTHOR]- Published
- 2024
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22. Phylodynamic and Epistatic Analysis of Coxsackievirus A24 and Its Variant.
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Cheng, Chia-Chi, Chu, Pei-Huan, Huang, Hui-Wen, Ke, Guan-Ming, Ke, Liang-Yin, and Chu, Pei-Yu
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ACUTE flaccid paralysis , *GENETIC recombination , *EPISTASIS (Genetics) , *MISSENSE mutation , *EYE infections - Abstract
Coxsackievirus A24 (CV-A24) is a human enterovirus that causes acute flaccid paralysis. However, a Coxsackievirus A24 variant (CV-A24v) is the most common cause of eye infections. The causes of these variable pathogenicity and tissue tropism remain unclear. To elucidate the phylodynamics of CV-A24 and CV-A24v, we analyzed a dataset of 66 strains using Bayesian phylodynamic approach, along with detailed sequence variation and epistatic analyses. Six CV-A24 strains available in GenBank and 60 CV-A24v strains, including 11 Taiwanese strains, were included in this study. The results revealed striking differences between CV-A24 and CV-A24v exhibiting long terminal branches in the phylogenetic tree, respectively. CV-A24v presented distinct ladder-like clustering, indicating immune escape mechanisms. Notably, 10 genetic recombination events in the 3D regions were identified. Furthermore, 11 missense mutation signatures were detected to differentiate CV-A24 and CV-A24v; among these mutations, the F810Y substitution may significantly affect the secondary structure of the GH loop of VP1 and subsequently affect the epitopes of the capsid proteins. In conclusion, this study provides critical insights into the evolutionary dynamics and epidemiological characteristics of CV-A24 and CV-A24v, and highlights the differences in viral evolution and tissue tropism. [ABSTRACT FROM AUTHOR]
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- 2024
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23. 异宗配合食用真菌双核体和单核体相关概念辨析.
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鲍大鹏, 徐建平, 潘迎捷, and 谭 琦
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LIFE history theory ,EDIBLE fungi ,PHENOMENOLOGICAL biology ,GENETIC recombination ,SEXUAL selection - Abstract
Copyright of Acta Edulis Fungi is the property of Acta Edulis Fungi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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24. Life cycle strategies in free‐living unicellular eukaryotes: Diversity, evolution, and current molecular tools to unravel the private life of microorganisms.
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Rizos, Iris, Frada, Miguel J., Bittner, Lucie, and Not, Fabrice
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SEXUAL cycle , *GENETIC recombination , *GENETIC markers , *DICTYOSTELIUM , *PROTISTA - Abstract
An astonishing range of morphologies and life strategies has arisen across the vast diversity of protists, allowing them to thrive in most environments. In model protists, like Tetrahymena, Dictyostelium, or Trypanosoma, life cycles involving multiple life stages with different morphologies have been well characterized. In contrast, knowledge of the life cycles of free‐living protists, which primarily consist of uncultivated environmental lineages, remains largely fragmentary. Various life stages and lineage‐specific cellular innovations have been observed in the field for uncultivated protists, but such innovations generally lack functional characterization and have unknown physiological and ecological roles. In the actual state of knowledge, evidence of sexual processes is confirmed for 20% of free‐living protist lineages. Nevertheless, at the onset of eukaryotic diversification, common molecular trends emerged to promote genetic recombination, establishing sex as an inherent feature of protists. Here, we review protist life cycles from the viewpoint of life cycle transitions and genetics across major eukaryotic lineages. We focus on the scarcely observed sexual cycle of free‐living protists, summarizing evidence for its existence and describing key genes governing its progression, as well as, current methods for studying the genetics of sexual cycles in both cultivable and uncultivated protist groups. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Effects of demographic history on recombination hotspots in soybean.
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McConaughy, Samantha, Amundsen, Keenan, and Hyten, David
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PLANT breeding , *SOYBEAN , *GENETIC recombination , *HAPLOTYPES , *LINKAGE disequilibrium , *GENETIC variation - Abstract
SUMMARY: Recombination is the primary mechanism underlying genetic improvement in populations and allows plant breeders to create new allelic combinations for agronomic improvement. Soybean [Glycine max (L.) Merr.] has gone through multiple genetic bottlenecks that have significantly affected its genetic diversity, linkage disequilibrium, and altered allele frequencies. To investigate the impact of genetic bottlenecks on recombination hotspots in soybeans, historical recombination was studied in three soybean populations. The populations were wild soybean [Glycine soja (Sieb. and Zucc.)], landraces, and North American elite soybean cultivars that have been genotyped with the SoySNP50K BeadChip. While each population after a genetic bottleneck had an increased average haplotype block size, they did not have a significant difference in the number of hotspots between each population. Instead, the increase in observed haplotype block size is likely due to an elimination of individuals that contained historical recombination at hotspots which decreased the observed rate of recombination for the hotspot after each genetic bottleneck. Conversely, heterochromatic DNA which has an increased haplotype block size compared to euchromatic DNA had a significantly different number of hotspots but not a significant difference in the average hotspot recombination rate. Previously identified genomic motifs associated with hotspots were also associated with hotspots found in the historical populations suggesting a common mechanism. This characterization of historical recombination hotspots in soybeans provides further insights into the effect genetic bottlenecks and selection have on recombination hotspots. Significance Statement: This manuscript provides a first look into soybean recombination hotspots across three diverse soybean populations. The populations used consist of a wild soybean population, landrace population, and North American elite soybean population. Through comparing the characteristics of the hotspots between the populations, this work provides insights into how selection and the genetic bottlenecks of domestication, introduction, and modern plant breeding have affected recombination hotspots and haplotype block structure in soybeans. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Phylogenomics identifies parents of naturally occurring tetraploid bananas.
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Lin, Yu-En, Chiu, Hui-Lung, Wu, Chung-Shien, and Chaw, Shu-Miaw
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BANANAS , *SEED harvesting , *GENETIC recombination , *REPRODUCTION , *OVUM , *DNA analysis , *TETRAPLOIDY , *GENETIC variation - Abstract
Background: Triploid bananas are almost sterile. However, we succeeded in harvesting seeds from two edible triploid banana individuals (Genotype: ABB) in our conservation repository where various wild diploid bananas were also grown. The resulting rare offspring survived to seedling stages. DNA content analyses reveal that they are tetraploid. Since bananas contain maternally inherited plastids and paternally inherited mitochondria, we sequenced and assembled plastomes and mitogenomes of these seedlings to trace their hybridization history. Results: The coding sequences of both organellar genomic scaffolds were extracted, aligned, and concatenated for constructing phylogenetic trees. Our results suggest that these tetraploid seedlings be derived from hybridization between edible triploid bananas and wild diploid Musa balbisiana (BB) individuals. We propose that generating female triploid gametes via apomeiosis may allow the triploid maternal bananas to produce viable seeds. Conclusions: Our study suggests a practical avenue towards expanding genetic recombination and increasing genetic diversity of banana breeding programs. Further cellular studies are needed to understand the fusion and developmental processes that lead to formation of hybrid embryos in banana reproduction, polyploidization, and evolution. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Enhanced recombination empowers the detection and mapping of Quantitative Trait Loci.
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Capilla-Pérez, Laia, Solier, Victor, Gilbault, Elodie, Lian, Qichao, Goel, Manish, Huettel, Bruno, Keurentjes, Joost J. B., Loudet, Olivier, and Mercier, Raphael
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LOCUS (Genetics) , *HOMOLOGOUS chromosomes , *GENETIC recombination , *PLANT breeding , *CHROMOSOMES , *GENOME editing , *ARABIDOPSIS thaliana - Abstract
Modern plant breeding, such as genomic selection and gene editing, is based on the knowledge of the genetic architecture of desired traits. Quantitative trait loci (QTL) analysis, which combines high throughput phenotyping and genotyping of segregating populations, is a powerful tool to identify these genetic determinants and to decipher the underlying mechanisms. However, meiotic recombination, which shuffles genetic information between generations, is limited: Typically only one to two exchange points, called crossovers, occur between a pair of homologous chromosomes. Here we test the effect on QTL analysis of boosting recombination, by mutating the anti-crossover factors RECQ4 and FIGL1 in Arabidopsis thaliana full hybrids and lines in which a single chromosome is hybrid. We show that increasing recombination ~6-fold empowers the detection and resolution of QTLs, reaching the gene scale with only a few hundred plants. Further, enhanced recombination unmasks some secondary QTLs undetected under normal recombination. These results show the benefits of enhanced recombination to decipher the genetic bases of traits. A quantitative genetic analysis on Arabidopsis mutants shows that increasing the frequency of meiotic crossovers boosts the detection and mapping of Quantitative Trait Loci (QTL). [ABSTRACT FROM AUTHOR]
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- 2024
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28. Anatomy Study to the Reproductive System in the Female Scorpions Androctonus Crassicauda.
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Al-Azawi, Zeina N.
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GENITALIA , *GENETIC recombination , *SCORPIONS , *ANATOMY , *FERTILITY - Abstract
Objectives: This study has investigated the anatomy of the reproductive system in the female scorpion Androctonus Crassicauda. Methods: Eight adult females were collected and dissected to investigate the structure and function of their reproductive organs. The adults female of scorpion Androctonus Crassicauda belonging to family Buthidae and the females of scorpion Androctonus Crassicauda were collected from provinces Baghdad and Wasit. Measurements of various body parts were taken, and the internal anatomy was examined under a microscope. Results: In general studies showed the female of scorpions have the ovariuterus consists of a reticular net are longitudinal and transverse ovarian tubes extend from third to seventh mesosomal segments, longitudinal ovarian tubes connected either by transverse ovarian tubes, but in the Buthidae family have an eight-celled reticular ovariuterus, that is five transverse ovarian tubes and the female Androctonus Crassicauda do not have five transverse tubes only the anterior and posterior forming a two-celled ovariuterus, and they have reproductive organs include ovaries, uterus, vagina. These results showed that female Androctonus Crassicauda has a simplified ovariuterus compared to other scorpions in the Buthidae family. It has only two cells because all the distal anastomosis are absent, the oocytes are contained in follicles directly in contact with the ovariuterus, Conclusions: This unique anatomy may be related to the reproductive strategies of this particular species, all scorpion juveniles derive some nutrients directly from females during development. The functions of these organs are involved in fertility, conception, pregnancy, and childbirth. The reproductive organs also have a significant influence on other aspects of health. The major function of the reproductive system in scorpions is to ensure the survival of the species and there are many systems in the body like the endocrine and urinary systems, which work to maintain homeostasis for survival. Reproduction plays a role in evolution as it creates variations via genetic recombination, therefore it is needed to have detailed study and experiments for the understanding of anatomy of the reproductive system in the Female Scorpions. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Novel Pan-Coronavirus 3CL Protease Inhibitor MK-7845: Biological and Pharmacological Profiling.
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Alvarez, Nadine, Adam, Gregory C., Howe, John A., Sharma, Vijeta, Zimmerman, Matthew D., Dolgov, Enriko, Rasheed, Risha, Nizar, Fatima, Sahay, Khushboo, Nelson, Andrew M., Park, Steven, Zhou, Xiaoyan, Burlein, Christine, Fay, John F., Iwamoto, Daniel V., Bahnck-Teets, Carolyn M., Getty, Krista L., Lin Goh, Shih, Salhab, Imad, and Smith, Keith
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SARS-CoV-2 , *MERS coronavirus , *CORONAVIRUSES , *GENETIC recombination , *COVID-19 pandemic , *LUNGS - Abstract
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After the extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction in viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice). [ABSTRACT FROM AUTHOR]
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- 2024
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30. A catalogue of recombination coldspots in interspecific tomato hybrids.
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Fuentes, Roven Rommel, Nieuwenhuis, Ronald, Chouaref, Jihed, Hesselink, Thamara, van Dooijeweert, Willem, van den Broeck, Hetty C., Schijlen, Elio, Schouten, Henk J., Bai, Yuling, Fransz, Paul, Stam, Maike, de Jong, Hans, Trivino, Sara Diaz, de Ridder, Dick, van Dijk, Aalt D. J., and Peters, Sander A.
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TOMATOES , *GENETIC variation , *TOMATO breeding , *GENETIC recombination , *CULTIVATED plants , *FOOD supply - Abstract
Increasing natural resistance and resilience in plants is key for ensuring food security within a changing climate. Breeders improve these traits by crossing cultivars with their wild relatives and introgressing specific alleles through meiotic recombination. However, some genomic regions are devoid of recombination especially in crosses between divergent genomes, limiting the combinations of desirable alleles. Here, we used pooled-pollen sequencing to build a map of recombinant and non-recombinant regions between tomato and five wild relatives commonly used for introgressive tomato breeding. We detected hybrid-specific recombination coldspots that underscore the role of structural variations in modifying recombination patterns and maintaining genetic linkage in interspecific crosses. Crossover regions and coldspots show strong association with specific TE superfamilies exhibiting differentially accessible chromatin between somatic and meiotic cells. About two-thirds of the genome are conserved coldspots, located mostly in the pericentromeres and enriched with retrotransposons. The coldspots also harbor genes associated with agronomic traits and stress resistance, revealing undesired consequences of linkage drag and possible barriers to breeding. We presented examples of linkage drag that can potentially be resolved by pairing tomato with other wild species. Overall, this catalogue will help breeders better understand crossover localization and make informed decisions on generating new tomato varieties. Author summary: Ensuring a stable food supply in a changing climate hinges on enhancing plants' natural defenses and resilience. Breeders achieve this by crossing cultivated plants with their wild counterparts, mixing specific gene variants through genetic recombination. Yet, in some cases, certain genomic areas lack this recombination, particularly when crossing diverse plant types, limiting the mix of beneficial genes. In this study we used a method called pooled-pollen sequencing to map regions where genetic recombination does and doesn't occur when breeding tomatoes with five wild relatives. We discovered specific regions where genetic exchange is rare, mainly due to structural differences in DNA. These regions tend to be rich in repetitive DNA sequences and are less likely to swap genes during reproduction. Importantly, many of these "recombination coldspots" contain genes related to plant health and stress resistance, inadvertently limiting the effectiveness of breeding efforts. By identifying these regions, breeders can now make more informed choices when developing new tomato varieties, potentially by incorporating genes from other wild species to overcome these limitations and improve crop resilience. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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31. EXPLORING NATURAL SELECTION SIGNATURES ON THE ALPHA-AMYLASE GENE OF NOVEL BACILLUS LICHENIFORMIS 208 STRAIN ISOLATED FROM A LOCAL HOT SPRING.
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ASAD, W., KIRAN, T., KHAN, M. H., SALEEM, F., ASAD, S. B., RASOOL, S. A., SHAH, T. A., AZIZ, T., ALHARBI, M., ALASMARI, A. F., and ALBEKAIRI, T. H.
- Subjects
NATURAL selection ,ASPARTIC acid ,BACILLUS licheniformis ,GENETIC recombination ,ALPHA-amylase ,AMYLASES - Abstract
This study emphasized the alpha-amylase gene from Bacillus licheniformis as this species has been witnessed as the most prolific bio-factories for the alpha amylase production on industrial scales with particular reference to its wide commercial applicability. In the present study, a gene encoding alpha-amylase from an indigenously isolated B. licheniformis 208 strain was PCR amplified and sequenced. The obtained 1313 bp long nucleotide sequence (GenBank KM27230) exhibited the closest match with its homologous genes in B. licheniformis ATCC 9945A and ATCC 14580 strains. Gene translation retrieved 437 amino acid long enzyme sequence and exhibits a molecular weight of 50231.8 KDa. Other computed parameters include isoelectric point (5.95), aliphatic index (67.4), instability index (27.45), and GRAVY (-0.627) values. The structure of alphaamylase 208 was found to exhibit a 17 residues long active site, a conserved catalytic site with 3 residues, and a ligand-binding site comprised of 3 residues. Secondary structure configuration in the alpha-amylase 208 was predominated with a-helix and random coils followed by extended strands. The number of ß-turns was found comparatively less. ITASSER assigned E.C number to the BLA 208 sequence was 3.2.1.1 with extracellular origin. Deduced tertiary structure of BLA 208 showed the 7 residues long active site comprising of histidine, arginine, aspartic acid, glutamic acid, tryptophan, histidine, and aspartic acid at position 122, 246, 248, 278, 280, 344, 345 respectively. Na, K, and Ca were observed as the ligand-binding sites existing as a metal triad. Natural selection analysis explains that the alpha-amylase gene in B. licheniformis species is under purifying or negative selection i.e. it stabilizes itself by removing the deleterious mutation. Recombination event analysis was done using GARD (Genetic algorithm for recombination detection). Although, it rather inferred the presence of two break points which were found insignificant when validated via Kishino-Hasegawa test which demonstrates topological incongruence. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Exploring the Accuracy and Limits of Algorithms for Localizing Recombination Breakpoints.
- Author
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Cen, Shi and Rasmussen, David A
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GENETIC recombination ,SEQUENCE alignment ,GENETIC algorithms ,GENOMES ,PHYLOGENY - Abstract
Phylogenetic methods are widely used to reconstruct the evolutionary relationships among species and individuals. However, recombination can obscure ancestral relationships as individuals may inherit different regions of their genome from different ancestors. It is, therefore, often necessary to detect recombination events, locate recombination breakpoints, and select recombination-free alignments prior to reconstructing phylogenetic trees. While many earlier studies have examined the power of different methods to detect recombination, very few have examined the ability of these methods to accurately locate recombination breakpoints. In this study, we simulated genome sequences based on ancestral recombination graphs and explored the accuracy of three popular recombination detection methods: MaxChi, 3SEQ, and Genetic Algorithm Recombination Detection. The accuracy of inferred breakpoint locations was evaluated along with the key factors contributing to variation in accuracy across datasets. While many different genomic features contribute to the variation in performance across methods, the number of informative sites consistent with the pattern of inheritance between parent and recombinant child sequences always has the greatest contribution to accuracy. While partitioning sequence alignments based on identified recombination breakpoints can greatly decrease phylogenetic error, the quality of phylogenetic reconstructions depends very little on how breakpoints are chosen to partition the alignment. Our work sheds light on how different features of recombinant genomes affect the performance of recombination detection methods and suggests best practices for reconstructing phylogenies based on recombination-free alignments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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33. Salivary Gland Tissue Recombination Can Modify Cell Fate.
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Sekiguchi, R., Martin, D., Doyle, A.D., Wang, S., and Yamada, K.M.
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SALIVARY glands ,RNA sequencing ,SUBMANDIBULAR gland ,PAROTID glands ,EPITHELIAL cells ,GENETIC recombination ,IMAGING systems in biology - Abstract
Although mesenchyme is essential for inducing the epithelium of ectodermal organs, its precise role in organ-specific epithelial fate determination remains poorly understood. To elucidate the roles of tissue interactions in cellular differentiation, we performed single-cell RNA sequencing and imaging analyses on recombined tissues, where mesenchyme and epithelium were switched ex vivo between two types of embryonic mouse salivary glands: the parotid gland (a serous gland) and the submandibular gland (a predominantly mucous gland). We found partial induction of molecules that define gland-specific acinar and myoepithelial cells in recombined salivary epithelium. The parotid epithelium recombined with submandibular mesenchyme began to express mucous acinar genes not intrinsic to the parotid gland. While myoepithelial cells do not normally line parotid acini, newly induced myoepithelial cells densely populated recombined parotid acini. However, mucous acinar and myoepithelial markers continued to be expressed in submandibular epithelial cells recombined with parotid mesenchyme. Consequently, some epithelial cells appeared to be plastic, such that their fate could still be modified in response to mesenchymal signaling, whereas other epithelial cells appeared to be already committed to a specific fate. We also discovered evidence for bidirectional induction: transcriptional changes were observed not only in the epithelium but also in the mesenchyme after heterotypic tissue recombination. For example, parotid epithelium induced the expression of muscle-related genes in submandibular fibroblasts that began to mimic parotid fibroblast gene expression. These studies provide the first comprehensive unbiased molecular characterization of tissue recombination approaches exploring the regulation of cell fate. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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34. Dissecting positive selection events and immunological drives during the evolution of adeno-associated virus lineages.
- Author
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Li, Lirong, Qin, Runkuan, Liu, Yunbo, Tseng, Yu-Shan, Zhang, Weihan, Yu, Lin, Mietzsch, Mario, Zou, Xinkai, Liu, Haizhou, Lu, Guangwen, Hu, Hongbo, Mckenna, Robert, Yang, Jinliang, Wei, Yuquan, Agbandje-Mckenna, Mavis, Hu, Jiankun, and Yang, Lin
- Subjects
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ADENO-associated virus , *GENE therapy , *GENETIC recombination , *GENETIC variation , *HUMAN genes , *ADENOVIRUSES - Abstract
Adeno-associated virus (AAV) serotypes from primates are being developed and clinically used as vectors for human gene therapy. However, the evolutionary mechanism of AAV variants is far from being understood, except that genetic recombination plays an important role. Furthermore, little is known about the interaction between AAV and its natural hosts, human and nonhuman primates. In this study, natural AAV capsid genes were subjected to systemic evolutionary analysis with a focus on selection drives during the diversification of AAV lineages. A number of positively selected sites were identified from these AAV lineages with functional relevance implied by their localization on the AAV structures. The selection drives of the two AAV2 capsid sites were further investigated in a series of biological experiments. These observations did not support the evolution of the site 410 of the AAV2 capsid driven by selection pressure from the human CD4+ T-cell response. However, positive selection on site 548 of the AAV2 capsid was directly related to host humoral immunity because of the profound effects of mutations at this site on the immune evasion of AAV variants from human neutralizing antibodies at both the individual and population levels. Overall, this work provides a novel interpretation of the genetic diversity and evolution of AAV lineages in their natural hosts, which may contribute to their further engineering and application in human gene therapy. Author summary: Adeno-associated virus (AAV) is a viral vector that is universally applied in human gene therapy. Despite their versatile applications in gene therapy, the origin and evolution of AAV serotypes have not been extensively studied. In this study, positive selection upon diversification of AAV capsid genes was carefully investigated by evolutionary analysis. Numerous diversifying selected sites were dispersed among the AAV lineages, and evolutionary pathways were inferred for two selected sites of the AAV2 capsid gene. Furthermore, the putative immunological drives underlying the selection of AAV2 capsid genes were experimentally dissected. This work provides a novel interpretation of the evolution and diversity of AAV serotypes and might be helpful for their engineering and application in gene therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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35. The pigeon circovirus evolution, epidemiology and interaction with the host immune system under One Loft Race rearing conditions.
- Author
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Stenzel, Tomasz, Dziewulska, Daria, Łukaszuk, Ewa, Custer, Joy M., De Koch, Matthew D., Kraberger, Simona, and Varsani, Arvind
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PIGEONS , *IMMUNE system , *GENETIC recombination , *VIRAL shedding , *GENETIC variation - Abstract
This study was aimed to investigate the frequency of PiCV recombination, the kinetics of PiCV viremia and shedding and the correlation between viral replication and host immune response in young pigeons subclinically infected with various PiCV variants and kept under conditions mimicking the OLR system. Fifteen racing pigeons originating from five breeding facilities were housed together for six weeks. Blood and cloacal swab samples were collected from birds every seven days to recover complete PiCV genomes and determine PiCV genetic diversity and recombination dynamics, as well as to assess virus shedding rate, level of viremia, expression of selected genes and level of anti-PiCV antibodies. Three hundred and eighty-eight complete PiCV genomes were obtained and thirteen genotypes were distinguished. Twenty-five recombination events were detected. Recombinants emerged during the first three weeks of the experiment which was consistent with the peak level of viremia and viral shedding. A further decrease in viremia and shedding partially corresponded with IFN-γ and MX1 gene expression and antibody dynamics. Considering the role of OLR pigeon rearing system in spreading infectious agents and allowing their recombination, it would be reasonable to reflect on the relevance of pigeon racing from both an animal welfare and epidemiological perspective. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Genetic heterogeneity of chicken anemia virus isolated in selected Egyptian provinces as a preliminary investigation.
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Abdel-Mawgod, Sara, Zanaty, Ali, Elhusseiny, Mohamed, Said, Dalia, Samir, Abdelhafez, Elsayed, Moataz M., Mahana, Osama, Said, Mahmoud, Hussein, Ahmed M., Hassan, Heba M., Selim, Abdullah, Shahien, Momtaz A., and Selim, Karim
- Subjects
CHICKENS ,GENETIC recombination ,H7N9 Influenza ,POULTRY farms ,POSTMORTEM changes ,STUNTED growth ,POLYMERASE chain reaction ,ANEMIA - Abstract
Chicken anemia virus (CAV) is a widespread and economically significant pathogen in the poultry industry. In this study 110 samples were collected from various poultry farms in selected Egyptian provinces during 2021-2022 and were tested against CAV by Polymerase Chain Reaction (PCR), revealing 22 positive samples with 20% incidence rate. Full sequence analysis of five selected CAV strains revealed genetic variations in VP1, VP2, and VP3 genes. Phylogenetic analysis grouped the Egyptian strains with reference viruses, mainly in group II, while vaccines like Del-Rose were categorized in group III. Recombination events were detected between an Egyptian strain (genotype II) and the Del-Rose vaccine strain (genotype III), indicating potential recombination between live vaccine strains and field isolates. To evaluate pathogenicity, one Egyptian isolate (F883-2022 CAV) and Del-Rose vaccine were tested in Specific Pathogen Free (SPF) chicks. Chicks in the positive group displayed clinical symptoms, including weakness and stunted growth, with postmortem findings consistent with CAV infection. The vaccine group showed milder symptoms and less severe postmortem changes. This study provides important insights into the genetic diversity of CAV in selected Egyptian poultry farms showing recombination event between field strain and vaccine strains, highlighting the need for advanced vaccination programs, especially for broilers. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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37. GENE PYRAMIDING THROUGH INTERCROSS POPULATIONS FOR BACTERIAL BLIGHT AND BROWN PLANTHOPPER RESISTANCE IN RICE.
- Author
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ABBASI, M. F., DIN, A. U., and ABBASI, F. M.
- Subjects
- *
NILAPARVATA lugens , *GENETIC recombination , *GENETIC variation , *BROWN rice , *XANTHOMONAS oryzae , *RICE diseases & pests - Abstract
Conventional breeding approaches often rely on bi-parental crosses, in which analysis occurs only on two alleles, and genetic recombination in such a population is insufficient, limiting genetic diversity. Multi-parent advanced generation inter-cross (MAGIC) populations display large sets of recombinant inbred lines (RILs) that exhibit a genetic mosaic of multiple founder parents. MAGIC populations result in a broader genetic base that has emerged as a powerful tool for genetic analysis and breeding for disease resistance in rice. This study developed the MAGIC population by intermating eight diverse founder parents. Conducting the molecular survey sought to analyze the genes resistant to bacterial blight (BB) and brown planthopper (BPH). The research used primers specific for Xa21, xa13, Xa4, and Bph1 in the polymerase chain reaction (PCR). The survey identified combinations of three genes: (Xa4+xa13+Xa21) in BR52 and (Xa4+xa13+Bph1) in BR43, BR44, BR48, and BR58. Two-gene combination (xa13 and Xa4) materialized in BR53, BR54, BR60, BR73, BR85, and BR86, while identifying a combination of xa13 and Bph1 in BR11, BR41, and BR99. Xa4 was present in 14, xa13 in six, and Bph1 in three lines. Screening the population against Xanthomonas oryzae validated the presence of BB-resistant genes. The consistent finding is that the RILs with a combination of two or more genes express a high level of resistance compared with the RILs with a single gene. The RILs with Xa4 and xa13 expressed more resistance than the lines with xa13 and Bph1. Employing the MAGIC populations approach remains to be effective for gene pyramiding. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Development and Validation of an Enzyme-Linked Immunosorbent Assay-Based Protocol for Evaluation of Respiratory Syncytial Virus Vaccines.
- Author
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Nham, Eliel, Jang, A-Yeung, Ji, Hyun Jung, Ahn, Ki Bum, Bae, Joon-Yong, Park, Man-Seong, Yoon, Jin Gu, Seong, Hye, Noh, Ji Yun, Cheong, Hee Jin, Kim, Woo Joo, Seo, Ho Seong, and Song, Joon Young
- Subjects
- *
RESPIRATORY syncytial virus , *VIRAL vaccines , *RESPIRATORY syncytial virus infection vaccines , *ENZYME-linked immunosorbent assay , *GENETIC recombination , *IMMUNOGLOBULIN G , *ALKALINE phosphatase - Abstract
Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. High-Frequency Recombination of Human Adenovirus in Children with Acute Respiratory Tract Infections in Beijing, China.
- Author
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Wang, Fangming, De, Ri, Han, Zhenzhi, Xu, Yanpeng, Zhu, Runan, Sun, Yu, Chen, Dongmei, Zhou, Yutong, Guo, Qi, Qu, Dong, Cao, Ling, Liu, Liying, and Zhao, Linqing
- Subjects
- *
RESPIRATORY infections , *ADENOVIRUSES , *GENETIC recombination , *NUCLEOTIDE sequencing , *CHILD patients , *MIXED infections - Abstract
Recombination events in human adenovirus (HAdV) have led to some new highly pathogenic or infectious types. It is vital to monitor recombinant HAdVs, especially in children with acute respiratory tract infections (ARIs). In the retrospective study, HAdV positive specimens were collected from pediatric patients with ARIs during 2015 to 2021, then typed by sequence analysis of the penton base, hexon and fiber gene sequence. For those with inconsistent typing results, a modified method with species-specific primer sets of a fiber gene sequence was developed to distinguish co-infections of different types from recombinant HAdV infections. Then, plaque assays combined with meta-genomic next-generation sequencing (mNGS) were used to reveal the HAdV genomic characteristics. There were 466 cases positive for HAdV DNA (2.89%, 466/16,097) and 350 (75.11%, 350/466) successfully typed with the most prevalent types HAdV-B3 (56.57%, 198/350) and HAdV-B7 (32.00%, 112/350), followed by HAdV-C1 (6.00%, 21/350). Among 35 cases (7.51%, 35/466) with inconsistent typing results, nine cases were confirmed as co-infections by different types of HAdVs, and 26 cases as recombinant HAdVs in six genetic patterns primarily clustered to species C (25 cases) in pattern 1–5, or species D (1 case) in pattern 6. The novel recombinant HAdV of species D was identified with multiple recombinant events among HAdV-D53, HAdV-D64, and HAdV-D8, and officially named as HAdV-D115. High-frequency recombination of HAdVs in six genetic recombination patterns were identified among children with ARIs in Beijing. Specifically, there is a novel Adenovirus D human/CHN/S8130/2023/115[P22H8F8] designed as HAdV D115. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. A Knowledge-Guided Multi-Objective Shuffled Frog Leaping Algorithm for Dynamic Multi-Depot Multi-Trip Vehicle Routing Problem.
- Author
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Zhao, Yun, Shen, Xiaoning, and Ge, Zhongpei
- Subjects
- *
VEHICLE routing problem , *OPTIMIZATION algorithms , *PATTERN recognition systems , *GENETIC recombination , *ALGORITHMS , *TERMINALS (Transportation) , *FROGS - Abstract
Optimization algorithms have a wide range of applications in symmetry problems, such as graphs, networks, and pattern recognition. In this paper, a dynamic periodic multi-depot multi-trip vehicle routing model for scheduling test samples is constructed, which considers the differences in testing unit price and testing capacity of various agencies and introduces a cross-depot collaborative transport method. Both the cost and the testing time are minimized by determining the optimal sampling routes and testing agencies, subjecting to the constraints of vehicle capacity, number of vehicles, and delivery time. To solve the model, a knowledge-guided multi-objective shuffled frog leaping algorithm (KMOSFLA) is proposed. KMOSFLA adopts a convertible encoding mechanism to realize the diversified search in different search spaces. Three novel strategies are designed: the population initialization with historical information reuse, the leaping rule based on the greedy crossover and genetic recombination, and the objective-driven enhanced search. Systematic experimental studies are implemented. First, feasibility analyses of the model are carried out, where effectiveness of the cross-depot collaborative transport is validated and sensitivity analyses on two parameters (vehicle capacity and proportion of the third-party testing agencies) are performed. Then, the proposed algorithm KMOSFLA is compared with five state-of-the-art algorithms. Experimental results indicate that KMOSFLA can provide a set of non-dominated schedules with lower cost and shorter testing time in each scheduling period, which provides a reference for the dispatcher to make a final decision. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Linkage Mapping and Genome-Wide Association Study Identified Two Peanut Late Leaf Spot Resistance Loci, PLLSR-1 and PLLSR-2, Using Nested Association Mapping.
- Author
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Gangurde, Sunil S., Thompson, Ethan, Yaduru, Shasidhar, Hui Wang, Fountain, Jake C., Ye Chu, Ozias-Akins, Peggy, Isleib, Thomas G., Holbrook, Corley, Dutta, Bhabesh, Culbreath, Albert K., Pandey, Manish K., and Baozhu Guo
- Subjects
- *
LOCUS (Genetics) , *GENOME-wide association studies , *GENETIC recombination , *LEAF spots , *SINGLE nucleotide polymorphisms , *POLLEN - Abstract
Identification of candidate genes and molecular markers for late leaf spot (LLS) disease resistance in peanut (Arachis hypogaea) has been a focus of molecular breeding for the U.S. industry-funded peanut genome project. Efforts have been hindered by limited mapping resolution due to low levels of genetic recombination and marker density available in traditional biparental mapping populations. To address this, a multi-parental nested association mapping population has been genotyped with the peanut 58K single-nucleotide polymorphism (SNP) array and phenotyped for LLS severity in the field for 3 years. Joint linkage-based quantitative trait locus (QTL) mapping identified nine QTLs for LLS resistance with significant phenotypic variance explained up to 47.7%. A genome-wide association study identified 13 SNPs consistently associated with LLS resistance. Two genomic regions harboring the consistent QTLs and SNPs were identified from 1,336 to 1,520 kb (184 kb) on chromosome B02 and from 1,026.9 to 1,793.2 kb (767 kb) on chromosome B03, designated as peanut LLS resistance loci, PLLSR-1 and PLLSR-2, respectively. PLLSR-1 contains 10 nucleotide-binding site leucine-rich repeat disease resistance genes. A nucleotide-binding site leucine-rich repeat disease resistance gene, Arahy.VKVT6A, was also identified on homoeologous chromosome A02. PLLSR-2 contains five significant SNPs associated with five different genes encoding callose synthase, pollen defective in guidance protein, pentatricopeptide repeat, acyl-activating enzyme, and C2 GRAM domains-containing protein. This study highlights the power of multi-parent populations such as nested association mapping for genetic mapping and marker-trait association studies in peanuts. Validation of these two LLS resistance loci will be needed for marker-assisted breeding. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. Characterization of a novel cfr/fexA-carrying SCCmec variant from a Mammaliicoccus sciuri isolated from henhouses.
- Author
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Xiao, Jia, Guo, Yunqing, Zhang, Wenting, Hu, Qiao, Lu, Qin, Wen, Guoyuan, Shao, Huabin, Cheng, Zhenyu, Luo, Qingping, and Zhang, Tengfei
- Subjects
- *
MOBILE genetic elements , *GENETIC recombination , *DNA modification & restriction , *POULTRY farms , *HEART sounds , *TRANSPOSONS - Abstract
The article discusses the characterization of a novel composite SCCmec ⅢA variant from a multi-resistant M. sciuri strain isolated from a henhouse in China. The strain, WHA07, exhibited resistance to oxacillin, linezolid, and florfenicol, and contained resistance genes such as cfr, fexA, tet(M), and qacG. The study provides evidence of the integrative recombination of cfr and fexA from plasmid to mobile SCCmec element in the chromosome, suggesting potential transfer of these resistance genes among staphylococci. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
43. Genetic recombination-mediated evolutionary interactions between phages of potential industrial importance and prophages of their hosts within or across the domains of Escherichia, Listeria, Salmonella, Campylobacter, and Staphylococcus
- Author
-
Saba Kobakhidze, Stylianos Koulouris, Nata Kakabadze, and Mamuka Kotetishvili
- Subjects
Bacteriophage ,Phage ,Prophage ,Genetic recombination ,Lateral genetic transfer ,Intergeneric recombination ,Microbiology ,QR1-502 - Abstract
Abstract Background The in-depth understanding of the role of lateral genetic transfer (LGT) in phage-prophage interactions is essential to rationalizing phage applications for human and animal therapy, as well as for food and environmental safety. This in silico study aimed to detect LGT between phages of potential industrial importance and their hosts. Methods A large array of genetic recombination detection algorithms, implemented in SplitsTree and RDP4, was applied to detect LGT between various Escherichia, Listeria, Salmonella, Campylobacter, Staphylococcus, Pseudomonas, and Vibrio phages and their hosts. PHASTER and RAST were employed respectively to identify prophages across the host genome and to annotate LGT-affected genes with unknown functions. PhageAI was used to gain deeper insights into the life cycle history of recombined phages. Results The split decomposition inferences (bootstrap values: 91.3–100; fit: 91.433-100), coupled with the Phi (0.0-2.836E-12) and RDP4 (P being well below 0.05) statistics, provided strong evidence for LGT between certain Escherichia, Listeria, Salmonella, and Campylobacter virulent phages and prophages of their hosts. The LGT events entailed mainly the phage genes encoding for hypothetical proteins, while some of these genetic loci appeared to have been affected even by intergeneric recombination in specific E. coli and S. enterica virulent phages when interacting with their host prophages. Moreover, it is shown that certain L. monocytogenes virulent phages could serve at least as the donors of the gene loci, involved in encoding for the basal promoter specificity factor, for L. monocytogenes. In contrast, the large genetic clusters were determined to have been simultaneously exchanged by many S. aureus prophages and some Staphylococcus temperate phages proposed earlier as potential therapeutic candidates (in their native or modified state). The above genetic clusters were found to encompass multiple genes encoding for various proteins, such as e.g., phage tail proteins, the capsid and scaffold proteins, holins, and transcriptional terminator proteins. Conclusions It is suggested that phage-prophage interactions, mediated by LGT (including intergeneric recombination), can have a far-reaching impact on the co-evolutionary trajectories of industrial phages and their hosts especially when excessively present across microbially rich environments.
- Published
- 2024
- Full Text
- View/download PDF
44. Genetic landscape of interval and screen detected breast cancer.
- Author
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Mills, Charlie, Sud, Amit, Everall, Andrew, Chubb, Daniel, Lawrence, Samuel E. D., Kinnersley, Ben, Cornish, Alex J., Bentham, Robert, and Houlston, Richard S.
- Subjects
BREAST cancer ,MEDICAL screening ,HOMOLOGOUS recombination ,WHOLE genome sequencing ,GENETIC recombination ,GENE targeting ,CANCER invasiveness - Abstract
Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Bridging the gap between the evolutionary dynamics and the molecular mechanisms of meiosis: A model based exploration of the PRDM9 intra-genomic Red Queen.
- Author
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Genestier, Alice, Duret, Laurent, and Lartillot, Nicolas
- Subjects
- *
GAMETOGENESIS , *MEIOSIS , *GENETIC recombination , *GENE conversion , *HOMOLOGOUS chromosomes - Abstract
Molecular dissection of meiotic recombination in mammals, combined with population-genetic and comparative studies, have revealed a complex evolutionary dynamic characterized by short-lived recombination hotspots. Hotspots are chromosome positions containing DNA sequences where the protein PRDM9 can bind and cause crossing-over. To explain these fast evolutionary dynamic, a so-called intra-genomic Red Queen model has been proposed, based on the interplay between two antagonistic forces: biased gene conversion, mediated by double-strand breaks, resulting in hotspot extinction (the hotspot conversion paradox), followed by positive selection favoring mutant PRDM9 alleles recognizing new sequence motifs. Although this model predicts many empirical observations, the exact causes of the positive selection acting on new PRDM9 alleles is still not well understood. In this direction, experiment on mouse hybrids have suggested that, in addition to targeting double strand breaks, PRDM9 has another role during meiosis. Specifically, PRDM9 symmetric binding (simultaneous binding at the same site on both homologues) would facilitate homology search and, as a result, the pairing of the homologues. Although discovered in hybrids, this second function of PRDM9 could also be involved in the evolutionary dynamic observed within populations. To address this point, here, we present a theoretical model of the evolutionary dynamic of meiotic recombination integrating current knowledge about the molecular function of PRDM9. Our modeling work gives important insights into the selective forces driving the turnover of recombination hotspots. Specifically, the reduced symmetrical binding of PRDM9 caused by the loss of high affinity binding sites induces a net positive selection eliciting new PRDM9 alleles recognizing new targets. The model also offers new insights about the influence of the gene dosage of PRDM9, which can paradoxically result in negative selection on new PRDM9 alleles entering the population, driving their eviction and thus reducing standing variation at this locus. Author summary: Meiosis is an important step in the eukaryotic life cycle, leading to the formation of gametes and implementing genetic mixing by recombination of paternal and maternal genomes. A key step of meiosis is the pairing of homologous chromosomes, which is required in order to distribute them evenly into the gametes. Chromosome pairing will also determine the exact position at which paternal and maternal chromosomes will exchange material. Research on the molecular basis of meiosis has revealed the role of a key gene, PRDM9. The protein encoded by PRDM9 binds to specific DNA sequences, by which it determines the location of recombination points. Symmetric binding of the protein (at the same position on the homologous chromosomes) also facilitates chromosome pairing. This molecular mechanism, however, has paradoxical consequences, among which the local destruction of the DNA sequences recognized by PRDM9, leading to their rapid loss at the level of the population over a short evolutionary time. In order to better understand why recombination is maintained over time despite this process, we have developed a simulation program implementing a model taking into account these molecular mechanisms. Our model makes realistic predictions about recombination evolution and confirms the important role played by PRDM9 during meiosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Genetic diversity and phylogeographic dynamics of avihepadnavirus: a comprehensive full-length genomic view.
- Author
-
Sikandar, Muhammad, Shah, Pir Tariq, and Li Xing
- Subjects
HEPATITIS B virus ,GENETIC variation ,SNOW goose ,VIRAL genomes ,HEPATITIS B ,GENETIC recombination ,CHLOROPLAST DNA ,BIRDS - Abstract
Avihepadnavirus is a genus of the Hepadnaviridae family. It primarily infects birds, including species of duck, geese, cranes, storks, and herons etc. To understand the genetic relatedness and evolutionary diversity among avihepadnavirus strains, a comprehensive analysis of the available 136 full-length viral genomes (n = 136) was conducted. The genomes were classified into two major genotypes, i.e., GI and GII. GI viruses were further classified into 8 sub-genotypes including DHBV-I (duck hepatitis B virus-I), DHBV-II (Snow goose Hepatitis B, SGHBV), DHBV-III, RGHBV (rossgoose hepatitis B virus), CHBV (crane hepatitis B virus), THBV (Tinamou hepatitis B virus), STHBV (stork hepatitis B virus), and HHBV (Heron hepatitis B virus). DHBV-I contains two sub-clades DHBV-Ia and DHBVIb. Parrot hepatitis B virus (PHBV) stains fall into GII which appeared as a separate phylogenetic branch/clade. All the subtypes of viruses in GI and GII seem to be genetically connected with viruses of DHBV-I by multiple mutational steps in phylogeographic analysis. Furthermore, 16 potential recombination events among different sub-genotypes in GI and one in GII were identified, but none of which is inter-genotypic between GI and GII. Overall, the results provide a whole picture of the genetic relatedness of avihepadnavirus strains, which may assist in the surveillance of virus spreading. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Genetic recombination-mediated evolutionary interactions between phages of potential industrial importance and prophages of their hosts within or across the domains of Escherichia, Listeria, Salmonella, Campylobacter, and Staphylococcus.
- Author
-
Kobakhidze, Saba, Koulouris, Stylianos, Kakabadze, Nata, and Kotetishvili, Mamuka
- Subjects
- *
INDUSTRIAL capacity , *LISTERIA , *ESCHERICHIA , *STAPHYLOCOCCUS , *ESCHERICHIA coli , *SALMONELLA enterica , *BACTERIOPHAGES - Abstract
Background: The in-depth understanding of the role of lateral genetic transfer (LGT) in phage-prophage interactions is essential to rationalizing phage applications for human and animal therapy, as well as for food and environmental safety. This in silico study aimed to detect LGT between phages of potential industrial importance and their hosts. Methods: A large array of genetic recombination detection algorithms, implemented in SplitsTree and RDP4, was applied to detect LGT between various Escherichia, Listeria, Salmonella, Campylobacter, Staphylococcus, Pseudomonas, and Vibrio phages and their hosts. PHASTER and RAST were employed respectively to identify prophages across the host genome and to annotate LGT-affected genes with unknown functions. PhageAI was used to gain deeper insights into the life cycle history of recombined phages. Results: The split decomposition inferences (bootstrap values: 91.3–100; fit: 91.433-100), coupled with the Phi (0.0-2.836E-12) and RDP4 (P being well below 0.05) statistics, provided strong evidence for LGT between certain Escherichia, Listeria, Salmonella, and Campylobacter virulent phages and prophages of their hosts. The LGT events entailed mainly the phage genes encoding for hypothetical proteins, while some of these genetic loci appeared to have been affected even by intergeneric recombination in specific E. coli and S. enterica virulent phages when interacting with their host prophages. Moreover, it is shown that certain L. monocytogenes virulent phages could serve at least as the donors of the gene loci, involved in encoding for the basal promoter specificity factor, for L. monocytogenes. In contrast, the large genetic clusters were determined to have been simultaneously exchanged by many S. aureus prophages and some Staphylococcus temperate phages proposed earlier as potential therapeutic candidates (in their native or modified state). The above genetic clusters were found to encompass multiple genes encoding for various proteins, such as e.g., phage tail proteins, the capsid and scaffold proteins, holins, and transcriptional terminator proteins. Conclusions: It is suggested that phage-prophage interactions, mediated by LGT (including intergeneric recombination), can have a far-reaching impact on the co-evolutionary trajectories of industrial phages and their hosts especially when excessively present across microbially rich environments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
48. Albumin promoter-driven FlpO expression induces efficient genetic recombination in mouse liver.
- Author
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Zhu, Xiaohui, Yang, Yan, Feng, Dongfeng, Wang, Oliver, Chen, Jiaxiang, Wang, Jiale, Wang, Bin, Liu, Yang, Edenfield, Brandy H., Haddock, Ashley N., Wang, Ying, Patel, Tushar, Bi, Yan, and Ji, Baoan
- Subjects
- *
GENETIC recombination , *GENE expression , *BACTERIAL artificial chromosomes , *P53 antioncogene , *ALBUMINS , *TUMOR suppressor genes , *GENE targeting - Abstract
Tissue-specific gene manipulations are widely used in genetically engineered mouse models. A single recombinase system, such as the one using Alb-Cre, has been commonly used for liver-specific genetic manipulations. However, most diseases are complex, involving multiple genetic changes and various cell types. A dual recombinase system is required for conditionally modifying different genes sequentially in the same cell or inducing genetic changes in different cell types within the same organism. A FlpO cDNA was inserted between the last exon and 3′-UTR of the mouse albumin gene in a bacterial artificial chromosome (BAC-Alb-FlpO). The founders were crossed with various reporter mice to examine the efficiency of recombination. Liver cancer tumorigenesis was investigated by crossing the FlpO mice with FSF-KrasG12D mice and p53frt mice (KPF mice). BAC-Alb-FlpO mice exhibited highly efficient recombination capability in both hepatocytes and intrahepatic cholangiocytes. No recombination was observed in the duodenum and pancreatic cells. BAC-Alb-FlpO-mediated liver-specific expression of mutant KrasG12D and conditional deletion of p53 gene caused the development of liver cancer. Remarkably, liver cancer in these KPF mice manifested a distinctive mixed hepatocellular carcinoma and cholangiocarcinoma phenotype. A highly efficient and liver-specific BAC-Alb-FlpO mouse model was developed. In combination with other Cre lines, different genes can be manipulated sequentially in the same cell, or distinct genetic changes can be induced in different cell types of the same organism. NEW & NOTEWORTHY: A liver-specific Alb-FlpO mouse line was generated. By coupling it with other existing CreERT or Cre lines, the dual recombinase approach can enable sequential gene modifications within the same cell or across various cell types in an organism for liver research through temporal and spatial gene manipulations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. Markov chain composite likelihood and its application in genetic recombination model.
- Author
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Sun, Jianping, Lindsay, Bruce G., and Rhodes, Grace E.
- Subjects
- *
GENETIC recombination , *GENETIC models , *MARKOV processes , *GENOMICS , *BINARY sequences - Abstract
Phylogenetic Trees are critical in human genome research for investigating human evolution and identifying disease-associated genetic markers. New high-throughput genome sequencing technologies raise an urgent need to develop statistical methods that can construct phylogenetic trees from long genome sequences with quick computation speeds, while considering various biological complexities. Though an ancestral mixture model has been proposed [Chen SC, Lindsay BG. Building mixture trees from binary sequence data. Biometrika. 2006;93(4):843–860. doi: 10.1093/biomet/93.4.843] to this end by allowing genetic mutations over generations, another essential evolution factor, genetic recombination, is missed. Therefore, in this paper, we develop a novel genetic recombination model for tree construction and propose to use Markov chain composite likelihood (MCCL) to make model estimation computationally feasible. To further reduce computation complexity, a hierarchical estimator is constructed to estimate unknown ancestral distributions through MCCL. Simulation studies and real data example show that our proposed methods perform well and fast, so have the potential for implementation in long sequence genome data. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. VIM-type metallo-β-lactamase (MBL)-encoding genomic islands in Pseudomonas spp. in Poland: predominance of clc-like integrative and conjugative elements (ICEs).
- Author
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Urbanowicz, P, Izdebski, R, Biedrzycka, M, and Gniadkowski, M
- Subjects
- *
PSEUDOMONAS , *PSEUDOMONAS aeruginosa , *PSEUDOMONAS putida , *GENETIC recombination , *INTEGRONS , *DRUG resistance in microorganisms - Abstract
Objectives To characterize VIM-type metallo-β-lactamase (MBL)-encoding genomic islands (GIs) in Pseudomonas aeruginosa and P. putida group isolates from Polish hospitals from 2001–2015/16. Methods Twelve P. aeruginosa and 20 P. putida group isolates producing VIM-like MBLs were selected from a large collection of these based on epidemiological and typing data. The organisms represented all major epidemic genotypes of these species spread in Poland with chromosomally located bla VIM gene-carrying integrons. The previously determined short-read sequences were complemented by long-read sequencing in this study. The comparative structural analysis of the GIs used a variety of bioinformatic tools. Results Thirty different GIs with bla VIM integrons were identified in the 32 isolates, of which 24 GIs from 26 isolates were integrative and conjugative elements (ICEs) of the clc family. These in turn were dominated by 21 variants of the GI2/ICE 6441 subfamily with a total of 19 VIM integrons, each inserted in the same position within the ICE's Tn 21 -like transposon Tn 4380. The three other ICEs formed a novel ICE 6705 subfamily, lacking Tn 4380 and having different VIM integrons located in another site of the elements. The remaining six non-ICE GIs represented miscellaneous structures. The presence of various integrons in the same ICE sublineage, and of the same integron in different GIs, indicated circulation and recombination of the integron-carrying genetic platforms across Pseudomonas species/genotypes. Conclusions Despite the general diversity of the bla VIM-carrying GIs in Pseudomonas spp. in Poland, a clear predominance of broadly spread and rapidly evolving clc -type ICEs was documented, confirming their significant role in antimicrobial resistance epidemiology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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