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eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Thomas S McAlear ◽  
Susanne Bechstedt

Cells increase microtubule dynamics to make large rearrangements to their microtubule cytoskeleton during cell division. Changes in microtubule dynamics are essential for the formation and function of the mitotic spindle, and misregulation can lead to aneuploidy and cancer. Using in vitro reconstitution assays we show that the mitotic spindle protein Cytoskeleton-Associated Protein 2 (CKAP2) has a strong effect on nucleation of microtubules by lowering the critical tubulin concentration 100-fold. CKAP2 increases the apparent rate constant ka of microtubule growth by 50-fold and increases microtubule growth rates. In addition, CKAP2 strongly suppresses catastrophes. Our results identify CKAP2 as the most potent microtubule growth factor to date. These finding help explain CKAP2's role as an important spindle protein, proliferation marker, and oncogene.


2022 ◽  
Author(s):  
Qichao Lian ◽  
Victor Solier ◽  
Birgit Walkemeier ◽  
Bruno Huettel ◽  
Korbinian Schneeberger ◽  
...  

Meiotic recombination frequency varies along chromosomes and strongly correlates with sequence divergence. However, the causality underlying this correlation is unclear. To untangle the relationship between recombination landscapes and polymorphisms, we characterized the genome-wide recombination landscape in the absence of polymorphisms, using Arabidopsis thaliana homozygous inbred lines in which a few hundred genetic markers were introduced through mutagenesis. We found that megabase-scale recombination landscapes in inbred lines are strikingly similar to the recombination landscapes in hybrids, with the sole exception of heterozygous large rearrangements where recombination is prevented locally. In addition, we found that the megabase-scale recombination landscape can be accurately predicted by chromatin features. Our results show that polymorphisms are not causal for the shape of the megabase-scale recombination landscape, rather, favor alternative models in which recombination and chromatin shape sequence divergence across the genome.


Author(s):  
Jana Wold ◽  
Klaus-Peter Koepfli ◽  
Stephanie Galla ◽  
Carolyn J. Hogg ◽  
David Eccles ◽  
...  

Structural variants (SVs) are large rearrangements (> 50 bp) within the genome that impact gene function and the content and structure of chromosomes. As a result, SVs are a significant source of functional genomic variation, i.e. variation at genomic regions underpinning phenotype differences, that can have large effects on individual and population fitness. While there are increasing opportunities to investigate functional genomic variation in threatened species via single nucleotide polymorphism (SNP) datasets, SVs remain understudied despite their potential influence on fitness traits of conservation interest. In this future-focused Opinion, we contend that characterizing SVs offers the conservation genomics community an exciting opportunity to complement SNP-based approaches to enhance species recovery. We also leverage the existing literature–predominantly in human health, agriculture and eco-evolutionary biology–to identify approaches for readily characterizing SVs and consider how integrating these into the conservation genomics toolbox may transform the way we manage some of the world’s most threatened species.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254101
Author(s):  
Fatiha Salmi ◽  
Fatima Maachi ◽  
Amal Tazzite ◽  
Rachid Aboutaib ◽  
Jamal Fekkak ◽  
...  

Prostate cancer is the most common male cancer in Morocco. Although sporadic forms account for a large proportion of patients, familial forms of prostate cancer are observed in 20% of cases and about 5% are due to hereditary transmission. Indeed, germline mutations in BRCA1/2 genes have been associated with prostate cancer risk. However, the spectrum of these mutations was not investigated in Moroccan Prostate cancer patients. Thereby, the aim of this study was to characterize and to estimate the prevalence of germline BRCA1/2 mutations and large rearrangements in Moroccan patients with familial prostate cancer. The entire coding regions and intron/exon boundaries of BRCA1 and BRCA2 genes have been analyzed by next generation sequencing (NGS) in a total of 30 familial prostate cancer patients. Three pathogenic mutations were detected in four unrelated patients (13.3%). One BRCA1 mutation (c.1953_1956delGAAA) and two BRCA2 mutations (c.7234_7235insG and BRCA2ΔE12). In addition, sixty-three distinct polymorphisms and unclassified variants have been found. Early identification of germline BRCA1/2 mutations may be relevant for the management of Moroccan prostate cancer patients.


Author(s):  
Jana Wold ◽  
Stephanie Galla ◽  
Anna Santure ◽  
David Eccles ◽  
Carolyn J. Hogg ◽  
...  

Structural variants (SVs) are large rearrangements (> 50 bp) within the genome that impact the form and structure of chromosomes. As a result, SVs are a significant source of functional genomic diversity, i.e. variation at genomic regions underpinning phenotype differences, that can have large effects on individual and population fitness. While there are increasing opportunities to investigate functional genomic diversity in threatened species via single nucleotide polymorphism (SNP) datasets, SVs remain understudied despite their potential influence on complex traits of conservation interest. In this future-focused Opinion, we contend that characterizing SVs offers the conservation genomics community an exciting opportunity to complement SNP-based approaches to enhance species recovery. We identify three critical resources to characterize SVs de novo: 1) High-quality, contiguous, annotated reference genome(s); 2) Whole genome resequence data from representative individuals of the target species/populations; and 3) Well-curated metadata including pedigrees. We also leverage the existing literature–predominantly in human health, agriculture and eco-evol biology–to identify pangenomic approaches for readily characterizing SVs and consider how integrating these into the conservation genomics toolbox may transform the way we intensively manage some of the world’s most threatened species.


Author(s):  
Jana Wold ◽  
Stephanie Galla ◽  
Anna Santure ◽  
David Eccles ◽  
Carolyn J. Hogg ◽  
...  

Structural variants (SVs) are large rearrangements (> 50 bp) within the genome that impact the form and structure of chromosomes. As a result, SVs are a significant source of functional genomic diversity, i.e. variation at genomic regions underpinning phenotype differences, that can have large effects on individual and population fitness. While there are increasing opportunities to investigate functional genomic diversity in threatened species via single nucleotide polymorphism (SNP) datasets, SVs remain understudied despite their potential influence on complex traits of conservation interest. In this future-focused Opinion, we contend that characterizing SVs offers the conservation genomics community an exciting opportunity to complement SNP-based approaches to enhance species recovery. We identify three critical resources to characterize SVs de novo: 1) High-quality, contiguous, annotated reference genome(s); 2) Whole genome resequence data from representative individuals of the target species/populations; and 3) Well-curated metadata including pedigrees. We also leverage the existing literature–predominantly in human health, agriculture and eco-evol biology–to identify pangenomic approaches for readily characterizing SVs and consider how integrating these into the conservation genomics toolbox may transform the way we intensively manage some of the world’s most threatened species.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dario A. Leon ◽  
Augusto Gonzalez

AbstractData from a long time evolution experiment with Escherichia Coli and from a large study on copy number variations in subjects with European ancestry are analyzed in order to argue that mutations can be described as Levy flights in the mutation space. These Levy flights have at least two components: random single-base substitutions and large DNA rearrangements. From the data, we get estimations for the time rates of both events and the size distribution function of large rearrangements.


2021 ◽  
Vol 7 (20) ◽  
pp. eabe4507
Author(s):  
Natalee D. Newton ◽  
Joshua M. Hardy ◽  
Naphak Modhiran ◽  
Leon E. Hugo ◽  
Alberto A. Amarilla ◽  
...  

Flaviviruses are the cause of severe human diseases transmitted by mosquitoes and ticks. These viruses use a potent fusion machinery to enter target cells that needs to be restrained during viral assembly and egress. A molecular chaperone, premembrane (prM) maintains the virus particles in an immature, fusion-incompetent state until they exit the cell. Taking advantage of an insect virus that produces particles that are both immature and infectious, we determined the structure of the first immature flavivirus with a complete spike by cryo–electron microscopy. Unexpectedly, the prM chaperone forms a supporting pillar that maintains the immature spike in an asymmetric and upright state, primed for large rearrangements upon acidification. The collapse of the spike along a path defined by the prM chaperone is required, and its inhibition by a multivalent immunoglobulin M blocks infection. The revised architecture and collapse model are likely to be conserved across flaviviruses.


2021 ◽  
Vol 10 (6) ◽  
pp. 1183
Author(s):  
Madalina Nicoleta Nan ◽  
Rosa Roig ◽  
Susana Martínez ◽  
Jose Rives ◽  
Eulàlia Urgell ◽  
...  

The most common form of congenital adrenal hyperplasia (CAH) results from a deficiency of the 21-hydroxylase enzyme (21-OHD), presenting with a broad spectrum of clinical phenotypes according to the CYP21A2 gene mutations. Of the 59 patients with suspected CAH, 62.7% presented a positive genetic result. Of them, 78.4% and 18.9% presented with non-classical and classical forms, respectively. An overall phenotype-genotype correlation of 88.9% was observed. Biochemically, 17-hydroxiprogesterone concentrations were significantly higher in genetically confirmed patients. Genetically, 36 patients presented with previously reported pathogenic variants, and one presented a new variant in homozygosis. Among the 74 alleles tested, point mutations were found in 89.2% and large rearrangements were found in the rest. The most prevalent pathogenic variant was p.(Val282Leu). The inclusion of relatives revealed one further case. Interestingly, 87.5% of relatives were carriers of a pathogenic variant, including two siblings initially classified as genetically positive. In addition, the study of male partners with gestational desire identified several carriers of mild mutations. Studying the allelic distribution of the variants also allowed for reclassifying one patient. In conclusion, a genetic approach including Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, and allelic distribution of the pathogenic variants represents a beneficial tool for better classifying patients with 21-OHD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naoya Yanagisawa ◽  
Rei Kurita

AbstractFoams can be ubiquitously observed in nature and in industrial products. Despite the relevance of their properties to deformation, fluidity, and collapse, all of which are essential for applications, there are few experimental studies of collective relaxation dynamics in a wet foam. Here, we directly observe how the relaxation dynamics changes with increasing liquid fraction in both monodisperse and polydisperse two-dimensional foams. As we increase the liquid fraction, we quantitatively characterize the slowing-down of the relaxation, and the increase of the correlation length. We also find two different relaxation modes which depend on the size distribution of the bubbles. It suggests that the bubbles which are simply near to each other play an important role in large rearrangements, not just those in direct contact. Finally, we confirm the generality of our experimental findings by a numerical simulation for the relaxation process of wet foams.


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