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Jeremie Vandenplas, Mario P L Calus, Gregor Gorjanc
This study presents a method for genomic prediction that uses individual-level data and summary statistics from multiple populations. Genome-wide markers are nowadays widely used to predict complex traits, and genomic prediction using multi-population data is an appealing approach to achieve higher prediction accuracies. However, sharing of individual-level data across populations is not always possible. We present a method that enables integration of summary statistics from separate analyses with the available individual-level data...
July 18, 2018: Genetics
Maria Cristina Gambetta, Eileen E M Furlong
Insulator binding proteins (IBPs) play an important role in regulating gene expression by binding to specific DNA sites to facilitate appropriate gene regulation. There are several IBPs in Drosophila , each defined by their ability to insulate target gene promoters in transgenic assays from the activating or silencing effects of neighboring regulatory elements. Of these, only CCCTC-binding factor (CTCF) has an obvious ortholog in Mammals. CTCF is essential for mammalian cell viability and is an important regulator of genome architecture...
July 18, 2018: Genetics
Sultan Ciftci-Yilmaz, Wei-Chun Au, Prashant K Mishra, Jessica R Eisenstatt, Joy Chang, Anthony R Dawson, Iris Zhu, Mahfuzur Rahman, Sven Bilke, Michael Costanzo, Anastasia Baryshnikova, Chad L Myers, Paul S Meltzer, David Landsman, Richard E Baker, Charles Boone, Munira A Basrai
Centromeric localization of the evolutionarily conserved centromere-specific histone H3 variant CENP-A (Cse4 in yeast) is essential for faithful chromosome segregation. Overexpression and mislocalization of CENP-A leads to chromosome segregation defects in yeast, flies, and human cells. Overexpression of CENP-A has been observed in human cancers; however, the molecular mechanisms preventing CENP-A mislocalization are not fully understood. Here, we used a genome-wide Synthetic Genetic Array (SGA) to identify gene deletions that exhibit synthetic dosage lethality (SDL) when Cse4 is overexpressed...
July 16, 2018: Genetics
Daria Radchenko, Ines Teichert, Stefanie Pöggeler, Ulrich Kück
The supramolecular striatin-interacting phosphatases and kinases (STRIPAK) complex is conserved from yeast to human and regulates a variety of key biological processes. In animals, this complex consists of the scaffold protein striatin, the protein phosphatase 2A (PP2A), and kinases, such as germinal center kinase III (GCKIII) and GCKIV family members, as well as other associated proteins. The STRIPAK complex was identified as a negative regulator of the Hippo pathway, a large eukaryotic signaling network with a core composed of a GCK and a nuclear dbf-2 related (NDR) kinase...
July 16, 2018: Genetics
Beth L Dumont, Christina L Williams, Bee Ling Ng, Valerie Horncastle, Carol L Chambers, Lisa A McGraw, David Adams, Trudy F C Mackay, Matthew Breen
In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven interactions are required for meiotic progression and are essential for male fertility. Although the PAR fulfills key meiotic functions in most mammals, several exceptional species lack PAR-mediated sex chromosome associations at meiosis. Here, we leveraged the natural variation in meiotic sex chromosome programs present in North American voles ( Microtus ) to investigate the relationship between meiotic sex chromosome dynamics and X/Y sequence homology...
July 12, 2018: Genetics
Eunice López-Fuentes, Grecia Hernández-Hernández, Leonardo Castanedo, Guadalupe Gutiérrez-Escobedo, Katarzyna Oktaba, Alejandro De Las Peñas, Irene Castaño
Adherence, an important virulence factor, is mediated by the EPA (<u>Ep</u>ithelial <u>A</u>dhesin) genes in the opportunistic pathogen Candida glabrata Expression of adhesin-encoding genes requires tight regulation in order to respond to harsh environmental conditions within the host. The majority of EPA genes are localized in subtelomeric regions regulated by subtelomeric silencing, which depends mainly on Rap1 and the Sir proteins. In vitro adhesion to epithelial cells is primarily mediated by Epa1...
July 12, 2018: Genetics
Rakesh Bodhicharla, Ranjan Devkota, Mario Ruiz, Marc Pilon
Maintenance of membrane properties is an essential aspect of cellular homeostasis of which the regulatory mechanisms remain mostly uncharacterized. In C. elegans, the PAQR-2 and IGLR-2 proteins act together as a plasma membrane sensor that responds to decreased fluidity by promoting fatty acid desaturation, hence restoring membrane fluidity. Here, we used mosaic analysis for paqr-2 and iglr-2 , and tissue-specific paqr- 2 expression, to show that membrane homeostasis is achieved cell non-autonomously. Specifically, we found that expression of paqr-2 in hypodermis, gonad sheath cells or intestine is sufficient to suppress systemic paqr-2 mutant phenotypes including: tail tip morphology, membrane fluidity in intestinal cells, cold and glucose intolerance, vitellogenin transport to the germ line, germ cell development and brood size...
July 11, 2018: Genetics
Maria Alcaide-Gavilán, Rafael Lucena, Katherine Schubert, Karen Artiles, Jessica Zapata, Douglas R Kellogg
Nutrient availability, growth rate and cell size are closely linked. For example, in budding yeast, the rate of cell growth is proportional to nutrient availability, cell size is proportional to growth rate, and growth rate is proportional to cell size. Thus, cells grow slowly in poor nutrients and are nearly half the size of cells growing in rich nutrients. Moreover, large cells grow faster than small cells. A signaling network that surrounds Tor kinase complex 2 (TORC2) plays an important role in enforcing these proportional relationships...
July 9, 2018: Genetics
Brandt Warecki, William Sullivan
While it is known that micronuclei pose a serious risk to genomic integrity by undergoing chromothripsis, mechanisms preventing micronucleus formation remain poorly understood. Here, we investigate how late-segregating acentric chromosomes that would otherwise form micronuclei instead reintegrate into daughter nuclei by passing through Aurora B kinase-dependent channels in the nuclear envelope of Drosophila melanogaster neuroblasts. We find that localized concentrations of Aurora B preferentially phosphorylate H3(S10) on acentrics and their associated DNA tethers...
July 9, 2018: Genetics
Amanda Glaser-Schmitt, Aleksandra Zečić, John Parsch
Genetic variation influencing levels of gene expression is abundant in natural populations and may exert its effects through complex mechanisms that depend on an organism's genetic background and the tissue in which expression is measured. We investigated natural variation in gene expression in the Malpighian tubules of three inbred Drosophila melanogaster strains and their F1 hybrids. One of the strains was from a population in the species' ancestral range (Zambia), while the other two were from a more recently derived population (Sweden)...
July 5, 2018: Genetics
Matthew Robert Paul, Tovah Elise Markowitz, Andreas Hochwagen, Sevinç Ercan
Condensins are broadly conserved chromosome organizers that function in chromatin compaction and transcriptional regulation, but to what extent these two functions are linked has remained unclear. Here, we analyzed the effect of condensin inactivation on genome compaction and global gene expression in the yeast Saccharomyces cerevisiae by performing spike-in-controlled 3C-seq and mRNA-seq analysis. 3C-seq analysis shows that acute condensin inactivation leads to a global decrease in close-range intra-chromosomal interactions as well as more specific losses of inter-chromosomal tRNA gene clustering...
July 3, 2018: Genetics
Yangqing Deng, Wei Pan
It is useful to detect allelic heterogeneity (AH), i.e. the presence of multiple causal SNPs in a locus, which for example may guide developing new methods for fine mapping and may determine how to interpret an appearing epistasis. In contrast to Mendelian traits, the existence and extent of AH for complex traits had been largely unknown until Hormozdiari et al. proposed a Bayesian method, called causal variants identification in associated regions (CAVIAR), and uncovered wide-spread AH in complex traits. However, there are several limitations with CAVIAR...
June 29, 2018: Genetics
Hikmat Al-Hashimi, David H Hall, Brian D Ackley, Erik A Lundquist, Matthew Buechner
The excretory canals of Caenorhabditis elegans are a model for understanding the maintenance of apical morphology in narrow single-celled tubes. Light and electron microscopy shows that mutants in exc-2 start to form canals normally, but these swell to develop large fluid-filled cysts that lack a complete terminal web at the apical surface, and accumulate filamentous material in the canal lumen. Here, whole-genome sequencing and gene rescue show that exc-2 encodes intermediate filament protein IFC-2. EXC-2/IFC-2 protein, fluorescently tagged via CRISPR/Cas9, is located at the apical surface of the canals independently of other intermediate filament proteins...
June 26, 2018: Genetics
Ariz Mohammad, Kara Vanden Broek, Christopher Wang, Anahita Daryabeigi, Verena Jantsch, Dave Hansen, Tim Schedl
A major event in germline development is the transition from stem/progenitor cells to entry into meiosis and gametogenesis. This transition requires downregulation of mitotic cell cycle activity and upregulation of processes associated with meiosis. We identify the C. elegans SCFPROM-1 E3 ubiquitin ligase complex as functioning to downregulate mitotic cell cycle protein levels including CYE-1, WAPL-1 and KNL-2 at meiotic entry and, independently, promoting homologous chromosome pairing as a positive regulator of the CHK-2 kinase...
June 25, 2018: Genetics
Yudai Masuoka, Kouhei Toga, Christine A Nalepa, Kiyoto Maekawa
Sterile castes are a defining criterion of eusociality; investigating their evolutionary origins can critically advance theory. In termites, the soldier caste is regarded as the first acquired permanently sterile caste. Previous studies showed that juvenile hormone (JH) is the primary factor inducing soldier differentiation, and treatment of workers with artificial JH can generate presoldier differentiation. It follows that a shift from a typical hemimetabolous JH response might be required for soldier formation during the course of termite evolution within the cockroach clade...
June 22, 2018: Genetics
Michael Reidy, Shailesh Kumar, D Eric Anderson, Daniel C Masison
The Hsp90 chaperone is regulated by many co-chaperones that tune its activities, but how they act to coordinate various steps in the reaction cycle is unclear. The primary role of Saccharomyces cerevisiae Hsp70/Hsp90 co-chaperone Sti1 (Hop in mammals) is to bridge Hsp70 and Hsp90 to facilitate client transfer. Sti1 is not essential, so Hsp90 can interact with Hsp70 in vivo without Sti1. Nevertheless, many Hsp90 mutations make Sti1 necessary for viability, which points to sites of Hsp90 as important for Hsp70 interaction...
June 21, 2018: Genetics
Olga Martzoukou, George Diallinas, Sotiris Amillis
The AP-1 complex is essential for membrane protein traffic via its role in the pinching-off and sorting of secretory vesicles from the trans-Golgi and/or endosomes. While its essentiality is undisputed in metazoa, its role in simpler eukaryotes seems less clear. Here we dissect the role of AP-1 in the filamentous fungus Aspergillus nidulans and show that it is absolutely essential for growth due to its role in clathrin-dependent maintenance of polar traffic of specific membrane cargoes towards the apex of growing hyphae...
June 20, 2018: Genetics
Desiree L Goetting, Rony Soto, Cheryl Van Buskirk
Behavioral plasticity allows for context-dependent prioritization of competing drives, such as sleep and foraging. Despite the identification of neuropeptides and hormones implicated in dual control of sleep drive and appetite, our understanding of the mechanism underlying the conserved sleep-suppressing effect of food deprivation is limited. C. elegans provides an intriguing model for the dissection of sleep function and regulation, as these nematodes engage a quiescence program following exposure to noxious conditions, a phenomenon known as stress-induced sleep (SIS)...
June 20, 2018: Genetics
Yves F Widmer, Adem Bilican, Rémy Bruggmann, Simon G Sprecher
Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation...
June 20, 2018: Genetics
Nikita Deshpande, Victoria H Meller
Many heterogametic organisms adjust sex chromosome expression to accommodate differences in gene dosage. This requires selective recruitment of regulatory factors to the modulated chromosome. How these factors are localized to a chromosome with requisite accuracy is poorly understood. Drosophila melanogaster males increase expression from their single X chromosome. Identification of this chromosome involves cooperation between different classes of X-identity elements. The Chromatin Entry Sites (CES) recruit a chromatin-modifying complex that spreads into nearby genes and increases expression...
June 19, 2018: Genetics
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