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https://www.readbyqxmd.com/read/28710064/time-course-analysis-of-early-meiotic-prophase-events-informs-mechanisms-of-homolog-pairing-and-synapsis-in-caenorhabditis-elegans
#1
Susanna Mlynarczyk-Evans, Anne M Villeneuve
Segregation of homologous chromosomes during meiosis depends on their ability to reorganize within the nucleus, discriminate among potential partners, and stabilize pairwise associations through assembly of the synaptonemal complex (SC). Here we report a high-resolution time-course analysis of these key early events during Caenorhabditis elegans meiosis. Labeled nucleotides are incorporated specifically into the X chromosomes during the last two hours of S phase, a property we exploit to identify a highly synchronous cohort of nuclei...
July 14, 2017: Genetics
https://www.readbyqxmd.com/read/28706002/micrornas-that-contribute-to-coordinating-the-immune-response-in-drosophila-melanogaster
#2
Magda L Atilano, Marcus Glittenberg, Annabel Monteiro, Richard Copley, Petros Ligoxygakis
Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defences. Here, we have used Drosophila melanogaster to explore the contribution of individual or clusters of miRNAs in countering systemic C. albicans infection. From a total of 72 tested, we identify six miRNAs allelic mutant backgrounds that modulate the survival response to infection and ability to control pathogen number. These mutants also exhibit dysregulation of the Toll pathway target transcripts Drosomycin (Drs) and Immune-Induced Molecule 1 (IM1)...
July 13, 2017: Genetics
https://www.readbyqxmd.com/read/28696218/non-canonical-decapentaplegic-signaling-activates-matrix-metalloproteinase-1-to-restrict-hedgehog-activity-and-limit-ectopic-eye-differentiation-in-drosophila
#3
Poonam Aggarwal, Jayati Gera, Saikat Ghosh, Lolitika Mandal, Sudip Mandal
One of the pertinent issues associated with cellular plasticity is to understand how the delicate balance between the determined state of cells and the extent to which they can transdetermine is maintained. Employing the well-established model of generating ectopic eyes in developing wing discs of Drosophila by ectopic eyeless expression, we provide evidence for the genetic basis of this mechanism. By both loss-of-function and gain-of-function genetic analyses, we demonstrate that Matrix metalloproteinase 1 (Mmp1) plays an important role in regulating the extent of ectopic ommatidial differentiation...
July 10, 2017: Genetics
https://www.readbyqxmd.com/read/28696217/exact-calculation-of-the-joint-allele-frequency-spectrum-for-isolation-with-migration-models
#4
Andrew D Kern, Jody Hey
Population genomic datasets collected over the past decade have spurred interest in developing methods that can utilize massive numbers of loci for inference of demographic and selective histories of populations. The allele frequency spectrum (AFS) provides a convenient statistic for such analysis and accordingly much attention has been paid to predicting theoretical expectations of the AFS under a number of different models. However, to date, exact solutions for the joint AFS of two or more populations under models of migration and divergence have not been found...
July 10, 2017: Genetics
https://www.readbyqxmd.com/read/28696216/regulation-of-lysosomal-function-by-the-daf-16-forkhead-transcription-factor-couples-reproduction-to-aging-in-caenorhabditis-elegans
#5
Kunal Baxi, Ata Ghavidel, Brandon Waddell, Troy A Harkness, Carlos E de Carvalho
Aging in eukaryotes is accompanied by widespread deterioration of the somatic tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in Caenorhabditis elegans In adult worms lacking germ cells, the activation of the DAF-9/DAF-12 steroid signalling pathway in the gonad recruits DAF-16 activity in the intestine to promote longevity-associated phenotypes. However, the impact of this pathway on the fitness of normally reproducing animals is less clear. Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity, a critical regulator of the proteolytic output of these organelles, as a novel biomarker of aging in C...
July 10, 2017: Genetics
https://www.readbyqxmd.com/read/28696215/a-model-for-epigenetic-inhibition-via-transvection-in-the-mouse
#6
Juan D Rodriguez, Dexter A Myrick, Ilaria Falciatori, Michael A Christopher, Teresa W Lee, Gregory J Hannon, David J Katz
Transvection is broadly defined as the ability of one locus to affect its homologous locus in trans Although it was first discovered in the 1950s, there are only two known cases in mammals. Here, we report another instance of mammalian transvection induced by the Cre/LoxP system, which is widely used for conditional gene targeting in the mouse. We attempted to use the germline expressed Vasa-Cre transgene to engineer a mouse mutation, but observe a dramatic reduction of LoxP recombination in mice that inherit an already deleted LoxP allele in trans A similar phenomenon has previously been observed with another Cre that is expressed during meiosis, Sycp-1-Cre This second example of LoxP inhibition in trans reinforces the conclusion that certain meiotically expressed Cre alleles can initiate transvection in mammals...
July 10, 2017: Genetics
https://www.readbyqxmd.com/read/28679547/connected-gene-communities-underlie-transcriptional-changes-in-cornelia-de-lange-syndrome
#7
Imène Boudaoud, Éric Fournier, Audrey Baguette, Maxime Vallée, Fabien C Lamaze, Arnaud Droit, Steve Bilodeau
Cornelia de Lange syndrome is a complex multisystem developmental disorder caused by mutations in cohesin subunits and regulators. While its precise molecular mechanisms are not well defined, they point toward a global deregulation of the transcriptional gene expression program. Cohesin is associated with the boundaries of chromosome domains and with enhancer and promoter regions connecting the three-dimensional genome organization with transcriptional regulation. Here we show that connected gene communities, structures emerging from the interactions of noncoding regulatory elements and genes in the three-dimensional chromosomal space, provide a molecular explanation for the pathoetiology of Cornelia de Lange syndrome associated with mutations in the cohesin-loading factor NIPBL and the cohesin subunit SMC1A NIPBL and cohesin are important constituents of connected gene communities that are centrally positioned at noncoding regulatory elements...
July 5, 2017: Genetics
https://www.readbyqxmd.com/read/28679546/untangling-heteroplasmy-structure-and-evolution-of-an-atypical-mitochondrial-genome-by-pacbio-sequencing
#8
Jean Peccoud, Mohamed Amine Chebbi, Alexandre Cormier, Bouziane Moumen, Clément Gilbert, Isabelle Marcadé, Christopher Chandler, Richard Cordaux
The highly compact mitochondrial genome of terrestrial isopods (Oniscidae) presents two unusual features. First, several loci can individually encode two tRNAs, thanks to single-nucleotide polymorphisms at anticodon sites. Within-individual variation (heteroplasmy) at these loci is thought to have been maintained for millions of years because individuals that do not carry all tRNA genes die, resulting in strong balancing selection. Second, the oniscid mtDNA genome comes in two conformations: a ~14kb linear monomer and a ~28kb circular dimer comprising two monomer units fused in palindrome...
July 5, 2017: Genetics
https://www.readbyqxmd.com/read/28679545/decomposing-the-site-frequency-spectrum-the-impact-of-tree-topology-on-neutrality-tests
#9
Luca Ferretti, Alice Ledda, Thomas Wiehe, Guillaume Achaz, Sebastian E Ramos-Onsins
We investigate the dependence of the site frequency spectrum (SFS) on the topological structure of genealogical trees. We show that basic population genetic statistics-for instance estimators of θ or neutrality tests such as Tajima's D-can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape...
July 5, 2017: Genetics
https://www.readbyqxmd.com/read/28679544/risk-prediction-modeling-on-family-based-sequencing-data-using-a-random-field-method
#10
Yalu Wen, Alexandra Burt, Qing Lu
Family-based design is one of the most popular designs in genetic studies and has many unique features for risk prediction research. It is more robust against genetic heterogeneity, and the relatedness among family members can be informative for predicting individuals' risk for disease with polygenic and shared environmental components of risk. Despite these strengths, family-based designs have been used infrequently in current risk prediction studies, and their related statistical methods have been much less developed...
July 5, 2017: Genetics
https://www.readbyqxmd.com/read/28679543/tracing-genetic-exchange-and-biogeography-of-cryptococcus-neoformans-var-grubii-at-the-global-population-level
#11
Johanna Rhodes, Christopher A Desjardins, Sean M Sykes, Mathew A Beale, Mathieu Vanhove, Sharadha Sakthikumar, Yuan Chen, Sharvari Gujja, Sakina Saif, Anuradha Chowdhary, Daniel John Lawson, Vinicius Ponzio, Arnaldo Lopes Colombo, Wieland Meyer, David M Engelthaler, Ferry Hagen, Maria Teresa Illnait-Zaragozi, Alexandre Alanio, Jo-Marie Vreulink, Joseph Heitman, John R Perfect, Anastasia Litvintseva, Tihana Bicanic, Thomas S Harrison, Matthew C Fisher, Christina A Cuomo
Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically HIV/AIDS patients from developing countries. Despite the worldwide emergence of this ubiquitous infection, little is known about the global molecular epidemiology of this fungal pathogen. Here we sequence the genomes of 188 diverse isolates and characterized the major subdivisions, their relative diversity and the level of genetic exchange between them...
July 5, 2017: Genetics
https://www.readbyqxmd.com/read/28663238/remarkable-evolutionary-conservation-of-anti-obesity-adipose-wdtc1-homologs-in-animals-and-plants
#12
Eric Ducos, Valentin Vergès, Thomas Dugé de Bernonville, Nathalie Blanc, Nathalie Giglioli-Guivarc'h, Christelle Dutilleul
ASG2 (Altered Seed Germination 2) is a prenylated protein in Arabidopsis thaliana that participates to abscisic acid signaling and is proposed to act as a substrate adaptor for the DDB1-CUL4 E3 ubiquitin ligase complex. ASG2 harbors WD40 and TetratricoPeptide Repeat (TPR) domains, and resembles the well-conserved animal gene called ADP (anti-obesity factor ADIPOSE) in fly and WDTC1 (WD40 and TPR 1) in humans. Loss of function of WDTC1 results in an increase in adipocytes, fat accumulation and obesity. Anti-adipogenic functions of WDTC1 involve regulation of fat-related gene transcription, notably through its binding to histone deacetylases...
June 29, 2017: Genetics
https://www.readbyqxmd.com/read/28652378/caenorhabditis-elegans-ces-1-snail-represses-pig-1-melk-expression-to-control-asymmetric-cell-division
#13
Hai Wei, Bo Yan, Julien Gagneur, Barbara Conradt
Snail-like transcription factors affect stem cell function through mechanisms that are incompletely understood. In the C. elegans NSM neuroblast lineage, CES-1 Snail coordinates cell cycle progression and cell polarity to ensure the asymmetric division of the NSM neuroblast and the generation of two daughter cells of different sizes and fates. We have previously shown that CES-1 Snail controls cell cycle progression by repressing the expression of cdc-25.2 CDC25. However, the mechanism through which CES-1 Snail affects cell polarity has been elusive...
June 26, 2017: Genetics
https://www.readbyqxmd.com/read/28652377/causal-genetic-variation-underlying-metabolome-differences
#14
Devjanee Swain-Lenz, Igor Nikolisky, Jiye Cheng, Priya Sudarsanam, Darcy Nayler, Max V Staller, Barak A Cohen
An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals...
June 26, 2017: Genetics
https://www.readbyqxmd.com/read/28646043/an-efficient-flp-based-toolkit-for-spatiotemporal-control-of-gene-expression-in-caenorhabditis-elegans
#15
Celia María Muñoz-Jiménez, Cristina Ayuso, Agnieszka Dobrzynska, Antonio Torres, Patricia de la Cruz Ruiz, Peter Askjaer
Site-specific recombinases are potent tools to regulate gene expression. In particular, the Cre and FLP enzymes are widely used to either activate or inactivate genes in a precise spatiotemporal manner. Both recombinases work efficiently in the popular model organism Caenorhabditis elegans but their use in this nematode is still only sporadic. To increase the utility of the FLP system in C. elegans we have generated a series of single-copy transgenic strains that stably express an optimized version of FLP in specific tissues or by heat induction...
June 23, 2017: Genetics
https://www.readbyqxmd.com/read/28642272/networks-underpinning-symbiosis-revealed-through-cross-species-eqtl-mapping
#16
Yuelong Guo, Sylwia Fudali, Jacinta Gimeno, Peter DiGennaro, Stella Chang, Valerie M Williamson, David McK Bird, Dahlia M Nielsen
Organisms engage in extensive cross-species molecular dialogue, yet the underlying molecular actors are known for only a few interactions. Many techniques have been designed to uncover genes involved in signaling between organisms. Typically, these focus on only one of the partners. We developed an expression quantitative trait locus (eQTL) mapping-based approach to identify cause-and-effect relationships between genes from two partners engaged in an interspecific interaction. We demonstrated the approach by assaying expression of ninety-eight isogenic plants (Medicago truncatula), each inoculated with a genetically distinct line of the diploid parasitic nematode Meloidogyne hapla With this design, systematic differences in gene expression across host plants could be mapped to genetic polymorphisms of their infecting parasites...
June 22, 2017: Genetics
https://www.readbyqxmd.com/read/28642271/powerful-genetic-association-analysis-for-common-or-rare-variants-with-high-dimensional-structured-traits
#17
Xiang Zhan, Ni Zhao, Anna Plantinga, Timothy A Thornton, Karen N Conneely, Michael P Epstein, Michael C Wu
Many genetic association studies collect a wide range of complex traits. As these traits may be correlated and share a common genetic mechanism, joint analysis can be statistically more powerful and biologically more meaningful. However, most existing tests for multiple traits cannot be used for high-dimensional and possibly structured traits, such as network-structured transcriptomic pathway expressions. To overcome potential limitations, in this paper we propose the dual kernel-based association test (DKAT) for testing the association between multiple traits and multiple genetic variants, both common and rare...
June 22, 2017: Genetics
https://www.readbyqxmd.com/read/28642270/heritable-micro-environmental-variance-covaries-with-fitness-in-an-outbred-population-of-drosophila-serrata
#18
Jacqueline L Sztepanacz, Katrina McGuigan, Mark W Blows
The genetic basis of stochastic variation within a defined environment, and the consequences of such micro-environmental variance for fitness are poorly understood. Using a multigenerational breeding design in Drosophila serrata, we demonstrated that the micro-environmental variance in a set of morphological wing traits in a randomly mating population had significant additive genetic variance in most single wing traits. Although heritability was generally low (< 1%), coefficients of additive genetic variance were of a magnitude typical of other morphological traits, indicating that the micro-environmental variance is an evolvable trait...
June 22, 2017: Genetics
https://www.readbyqxmd.com/read/28637712/shrinking-daughters-rlm1-dependent-g1-s-checkpoint-maintains-saccharomyces-cerevisiae-daughter-cell-size-and-viability
#19
Sarah Piccirillo, Deepshikha Neog, David Spade, J David Van Horn, LeAnn M Tiede-Lewis, Sarah L Dallas, Tamas Kapros, Saul M Honigberg
The Rlm1 transcription factor is a target of the cell-wall integrity pathway. We report that an rlm1Δ; mutant grown on a non-fermentable carbon source at low osmolarity forms cell groups in which a mother cell is surrounded by smaller "satellite daughter" cells. Mother cells in these groups progressed through repeated rounds of cell division with normal rates of bud growth and genetic stability; however, these cells underwent precocious START relative to wild-type mothers. Thus, once activated, Rlm1 delays the transition from G1 to S, a mechanism we term the CW/START checkpoint...
June 21, 2017: Genetics
https://www.readbyqxmd.com/read/28637711/the-exon-junction-complex-and-srp54-contribute-to-drosophila-hedgehog-signaling-via-ci-rna-splicing
#20
Elisa Garcia Garcia, Jamie C Little, Daniel Kalderon
Hedgehog (Hh) regulates the Cubitus interruptus (Ci) transcription factor in Drosophila melanogaster by activating full-length Ci-155 and blocking processing to Ci-75 repressor. However, the interplay between regulation of Ci-155 levels and activity, as well as processing-independent mechanisms that affect Ci-155 levels have not been explored extensively. Here we identified Mago Nashi (Mago) and Y14 core Exon Junction Complex (EJC) proteins, as well as the Srp54 splicing factor as modifiers of Hh pathway activity under sensitized conditions...
June 21, 2017: Genetics
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