scholarly journals Genomic characterization of world's longest selection experiment in mouse reveals the complexity of polygenic traits.

2021 ◽  
Author(s):  
Sergio Eliseo Palma-Vera ◽  
Henry Reyer ◽  
Martina Langhammer ◽  
Norbert Reinsch ◽  
Lorena Derezanin ◽  
...  

A unique set of mouse outbred lines has been generated through selective breeding in the longest selection experiment ever conducted on mice. Over the course of >140 generations, selection on the control line has given rise to two extremely fertile lines (>20 pups per litter each), two giant growth lines (one lean, one obese) and one long-distance running line. Genomic analysis revealed line-specific patterns of genetic variation among lines and high levels of homozygosity within lines as a result of long-term intensive selection, genetic drift and isolation. Detection of line-specific patterns of genetic differentiation and structural variation revealed multiple candidate genes behind the improvement of the selected traits. We conclude that the genomes of these lines are rich in beneficial alleles for the respective selected traits and represent an invaluable resource for unraveling the polygenic basis of fertility, obesity, muscle growth and endurance fitness.

2021 ◽  
Vol 11 ◽  
Author(s):  
Jean-Luc Raoul ◽  
Marie-Françoise Heymann ◽  
Frédéric Dumont ◽  
Alain Morel ◽  
Hélène Senellart ◽  
...  

Temporal and spatial tumor heterogeneity can be observed in pancreatic neuroendocrine tumor. We report the case of a young woman with long term stabilization of a G2 metastatic pancreatic NET that, after pregnancy, suddenly progressed into one single liver metastasis corresponding to a transformation into G3 large-cell neuroendocrine cancer. The patient underwent liver resection (the progressive and one dormant metastasis). With a 45 months follow-up the patient is without evolutive disease. Exome sequencing of the two metastases revealed completely different genomic signatures and gene alterations: the dormant metastasis was MSS without any gene alteration; the poorly differentiated tumor was MSI, with gain of many mutations including MEN1, BCL2, MLH1 and TP53 corresponding to a mutational signature 11. Could temozolomide play a role in this transformation?


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5566-5566 ◽  
Author(s):  
Stephanie Lheureux ◽  
Jonathan A. Ledermann ◽  
Sarah Runswick ◽  
Darren R Hodgson ◽  
Kirsten Timms ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
S. Alousi ◽  
T. Salloum ◽  
H. Arabaghian ◽  
G. M. Matar ◽  
G. F. Araj ◽  
...  

Escherichia coli is responsible for a wide variety of community and hospital acquired extraintestinal infections, and the emergence of ESBL resistant isolates is a major clinical concern. In this study, we characterized the genomic attributes of an OXA-48 and CTX-M-3 producing E. coli EC-IMP153. Whole-genome initial assembly produced 146 contigs with a combined 5,504,170 bp in size and a G+C content of 50.5%. wgSNPs-based phylogenetic comparison with 36 publically available genomes was also performed. Comprehensive genomic analysis showed that EC-IMP153 belonged to sequence type ST-405 and harbored several resistance determinants including the β-lactam resistance genes blaOXA-48, blaCTX-M-3, blaTEM-1B, blaOXA-1, and blaCMY-70, aminoglycoside fyuA and aac(3)IId, tetracycline tet(A) and tet(R), and fluoroquinolone gyrA, parC, and mfd resistance determinants. Plasmids with the following incompatibility groups were detected in silico and confirmed using PBRT: IncI1-α, IncL, IncW, Col (BS512), and IncF. To our knowledge this is the first in-depth genomic analysis of an OXA-48 producing E. coli ST-405 isolated from a patient in Lebanon and linked to a blood stream infection. Continuous monitoring is necessary to better understand the continued diffusion of such pathogens, especially in view of the population movements triggered by unrest in the Middle East.


2019 ◽  
Author(s):  
Nathan A. Wyatt ◽  
Jonathan K. Richards ◽  
Robert S. Brueggeman ◽  
Timothy L. Friesen

AbstractPyrenophora teres f. teres causes net form net blotch of barley and is an economically important pathogen throughout the world. However, P. teres f. teres is lacking in the genomic resources necessary to characterize the mechanisms of virulence. Recently a high quality reference genome was generated for P. teres f. teres isolate 0-1. Here, we present the reference quality sequence and annotation of four new isolates and we use the five available P. teres f. teres genomes for an in-depth comparison resulting in the generation of hypotheses pertaining to the potential mechanisms and evolution of virulence. Comparative analyses were performed between all five P. teres f. teres genomes examining genomic organization, structural variations, and core and accessory genomic content, specifically focusing on the genomic characterization of known virulence loci and the localization of genes predicted to encode secreted and effector proteins. We showed that 14 of 15 currently published virulence quantitative trait loci (QTL) span accessory genomic regions consistent with these accessory regions being important drivers of host adaptation. Additionally, these accessory genomic regions were frequently found in sub-telomeric regions of chromosomes with 10 of the 14 accessory region QTL localizing to sub-telomeric regions. Comparative analysis of the sub-telomeric regions of P. teres f. teres chromosomes revealed translocation events where homology was detected between non-homologous chromosomes at a significantly higher rate than the rest of the genome. These results indicate that the sub-telomeric accessory genomic compartments not only harbor most of the known virulence loci, but also that these regions have the capacity to rapidly evolve.


Author(s):  
Jasvinder Singh ◽  
Anup Sharma ◽  
Nita Ahuja

Peritoneal malignancies and metastasis are traditionally approached as a terminal disease, however with multiple lines of clinical therapy; long-term survival can be achieved in selected patients using aggressive cytoreduction and hyperthermic intraperitoneal chemotherapy. This is especially true for Pseudomyxoma peritonei from appendiceal neoplasms, peritoneal mesothelioma and peritoneal metastasis from colorectal cancer. In this article, we discuss the nature of genomic alterations in these three peritoneal malignancies and their potential as prognostic and therapeutic markers in clinical decisions. Genomic characterization of malignancies using technological advances including what is now widely used and accepted next-generation genomic sequencing methods has identified genomic anomalies (i.e. mutations, epigenetic modifications, transcription and expression changes in RNA) which is used for targeted therapy, prognostication, surveillance and prediction of response to therapy.


2020 ◽  
Vol 15 (9) ◽  
pp. 713-721
Author(s):  
Qifeng Sun ◽  
Jiao Feng ◽  
Yigang Tong ◽  
Luhua Liang ◽  
Fei Zhai ◽  
...  

Aim: To characterize two plasmids p13294-KPC and pA1966-NR from clinical Klebsiella pneumoniae strains. Materials & methods: Plasmids p13294-KPC and pA1966-NR were fully sequenced and then detailed genomic analysis was performed in this work. The antimicrobial resistance phenotypes were determined. Results: p13294-KPC and pA1966-NR displayed IncpA1763-KPC:IncFIIK7 dual-replicon structures. The backbone of these two plasmids were closely related to each other. p13294-KPC contained two accessory modules, namely ΔIS Kpn25 and blaKPC-2 region, and the blaKPC-2 region carried a range of mobile elements and resistance gene blaKPC-2. while pA1966-NR contained four individual IS elements in its backbone and carried no resistance genes. Conclusion: This study provided a deeper insight into the genomic characterization of IncpA1763-KPC: IncFIIK7 type plasmids p13294-KPC and pA1966-NR.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 206-206
Author(s):  
Tom Murphy ◽  
Jennifer M Thomson ◽  
James Berardinelli ◽  
Brent Roeder

Abstract A long-term selection experiment was conducted in a Rambouillet flock from 1969 to 2017. The high (HL) and low lines (LL) were divergently selected based on a maternal reproductive index, and an unselected control line (CL) was also maintained. Adult ewe traits considered were NLB, greasy fleece weight (GFW), and body weight after fall weaning of their lambs (BW). Results indicated that NLB was greatest for HL (1.67 ± 0.01), intermediate for CL (1.48 ± 0.02), and least for LL (1.28 ± 0.01; P < 0.001). Ewe GFW was greatest for LL (3.9 ± 0.02 kg; P ≤ 0.01) but not different between HL (3.82 ± 0.02 kg) and CL (3.88 ± 0.02 kg; P = 0.08); whereas, BW was least for HL (61.7 ± 0.19 kg; P ≤ 0.01) and not different between LL (62.9 ± 0.21 kg) and CL (62.6 ± 0.25 kg; P = 0.58). Heritability was estimated to be low for NLB (0.13 ± 0.02) and moderate for GFW (0.55 ± 0.03) and BW (0.46 ± 0.04). Genetic correlations were estimated to be near zero between NLB and GFW (-0.07 ± 0.08) and NLB and BW (0.12 ± 0.08) and low between GFW and BW (0.29 ± 0.06). Trends for NLB predicted breeding value differed among all 3 lines (P < 0.01) and was positive for HL (0.012 ± 0.0002 lambs/birth year), negative for LL (-0.005 ± 0.0002), and small but positive for CL (0.002 ± 0.0002). Inbreeding rates were positive in all lines but greatest for HL (0.45 ± 0.005 %/birth year), intermediate in LL (0.37 ± 0.006), and lowest in CL (0.28 ± 0.006). Results indicated long-term phenotypic selection for reproductive rate was effective and not genetically antagonistic with wool production or mature BW.


2021 ◽  
Author(s):  
Krzysztof Maćkała ◽  
Dariusz Mroczek ◽  
Paweł Chmura ◽  
Marek Konefał ◽  
Damian Pawlik ◽  
...  

Abstract The aim of this research is to evaluate marathon performance and asses the influence of this long-distance running endurance exercise on the changes of muscle stiffness in recreational runners aged 50 + years. Thirty-one male long-distance runners aged 50–73 years participated in the experiment. The muscle stiffness of quadriceps and calves was measured in two independent sessions: the day before the marathon and 30 min after the completed marathon run using a Myoton device. The 42.195-km run was completed in 4.30,05 h ± 35.12 min, which indicates an intensity of 79.3% ± 7.1% of HRmax. The long-term, low-intensity running exercise (marathon) in older recreational runners, along with the low level of HRmax and VO2max showed no statistically significant changes in muscle stiffness (quadriceps and calves). There was reduced muscle stiffness, but only in the triceps of the calf in the dominant (left) leg. Moreover, in order to optimally evaluate the marathon and adequately prepare for the performance training programme, we need to consider the direct and indirect analyses of the running economy, running technique, and HRmax and VO2max and DOMS variables. These variables significantly affect the marathon exercise.


2013 ◽  
Vol 94 (8) ◽  
pp. 1888-1895 ◽  
Author(s):  
Abdelmadjid Djoumad ◽  
Don Stoltz ◽  
Catherine Béliveau ◽  
Brian Boyle ◽  
Lisa Kuhn ◽  
...  

Polydnaviruses (PDVs) are symbiotic viruses carried by endoparasitic wasps and transmitted to caterpillar hosts during parasitization. Although they share several features, including a segmented dsDNA genome, a unique life cycle where replication is restricted to the wasp host, and immunodepressive/developmental effects on the caterpillar host, PDVs carried by ichneumonid and braconid wasps (referred to as ichnoviruses and bracoviruses, respectively) have different evolutionary origins. In addition, ichnoviruses (IVs) form two distinct lineages, with viral entities found in wasps belonging to the subfamilies Campopleginae and Banchinae displaying strikingly different virion morphologies and genomic features. However, the current description for banchine IVs is based on the characterization of a single species, namely that of the Glypta fumiferanae IV (GfIV). Here we provide an ultrastructural and genomic analysis of a second banchine IV isolated from the wasp Apophua simplicipes, and we show that this virus shares many features with GfIV, including a multi-nucleocapsid virion, an aggregate genome size of ~300 kb, genome segments <5 kb, an impressively high degree of genome segmentation and a very similar gene content (same gene families in both viruses). Altogether, the data presented here confirm the existence of shared characteristics within this banchine IV lineage.


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