Regulation of ectopic heterochromatin-mediated epigenetic diversification by the JmjC family protein Epe1
by Masato Sorida, Takahiro Hirauchi, Hiroaki Ishizaki, Wataru Kaito, Atsushi Shimada, Chie Mori, Yuji Chikashige, Yasushi Hiraoka, Yutaka Suzuki, Yasuyuki Ohkawa, Hiroaki Kato, Shinya Takahata, Yota Murakami H3K9 methylation (H3K9me) is a conserved marker of heterochromatin, a transcriptionally silent chromatin structure. Knowledge of the mechanisms for regulating heterochromatin distribution is limited. The fission yeast JmjC domain-containing protein Epe1 localizes to heterochromatin mainly through its interaction with Swi6, a homologue of heterochromatin protein 1 (HP1), and directs JmjC-mediated H3K9me demethylationin...
Source: PLoS Genetics - June 17, 2019 Category: Genetics & Stem Cells Authors: Masato Sorida Source Type: research

Locus suicide recombination actively occurs on the functionally rearranged IgH allele in B-cells from inflamed human lymphoid tissues
by Iman Dalloul, Fran çois Boyer, Zeinab Dalloul, Amandine Pignarre, Gersende Caron, Thierry Fest, Fabrice Chatonnet, Céline Delaloy, Anne Durandy, Robin Jeannet, Emilie Lereclus, Hend Boutouil, Jean-Claude Aldigier, Sophie Péron, Sandrine Le Noir, Jeanne Cook-Moreau, Michel Cogné B-cell activation yields abundant cell death in parallel to clonal amplification and remodeling of immunoglobulin (Ig) genes by activation-induced deaminase (AID). AID promotes affinity maturation of Ig variable regions and class switch recombination (CSR) in mature B lymphocytes. In the IgH locus , these processes ar...
Source: PLoS Genetics - June 14, 2019 Category: Genetics & Stem Cells Authors: Iman Dalloul Source Type: research

Convergent genetic aberrations in murine and human T lineage acute lymphoblastic leukemias
by Benjamin J. Huang, Anica M. Wandler, Lauren K. Meyer, Monique Dail, Anneleen Daemen, Deepak Sampath, Qing Li, Xinyue Wang, Jasmine C. Wong, Joy Nakitandwe, James R. Downing, Jinghui Zhang, Barry S. Taylor, Kevin Shannon The lack of predictive preclinical models is a fundamental barrier to translating knowledge about the molecular pathogenesis of cancer into improved therapies. Insertional mutagenesis (IM) in mice is a robust strategy for generating malignancies that recapitulate the extensive inter- and intra-tum oral genetic heterogeneity found in advanced human cancers. While the central role of "driver" vi...
Source: PLoS Genetics - June 14, 2019 Category: Genetics & Stem Cells Authors: Benjamin J. Huang Source Type: research

Genetic and functional data identifying < i > Cd101 < /i > as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice
by Jochen Mattner, Javid P. Mohammed, Michael E. Fusakio, Claudia Giessler, Carl-Philipp Hackstein, Robert Opoka, Marius Wrage, Regina Schey, Jan Clark, Heather I. Fraser, Daniel B. Rainbow, Linda S. Wicker Type 1 diabetes (T1D) is a chronic multi-factorial disorder characterized by the immune-mediated destruction of insulin-producing pancreatic beta cells. Variations at a large number of genes influence susceptibility to spontaneous autoimmune T1D in non-obese diabetic (NOD) mice, one of the most fr equently studied animal models for human disease. The genetic analysis of these mice allowed the identification of many ins...
Source: PLoS Genetics - June 14, 2019 Category: Genetics & Stem Cells Authors: Jochen Mattner Source Type: research

Time of day and network reprogramming during drought induced CAM photosynthesis in < i > Sedum album < /i >
by Ching Man Wai, Sean E. Weise, Philip Ozersky, Todd C. Mockler, Todd P. Michael, Robert VanBuren Plants with facultative crassulacean acid metabolism (CAM) maximize performance through utilizing C3 or C4 photosynthesis under ideal conditions while temporally switching to CAM under water stress (drought). While genome-scale analyses of constitutive CAM plants suggest that time of day networks are shifted, or phased to the evening compared to C3, little is known for how the shift from C3 to CAM networks is modulated in drought induced CAM. Here we generate a draft genome for the drought-induced CAM-cycling speciesSedum al...
Source: PLoS Genetics - June 14, 2019 Category: Genetics & Stem Cells Authors: Ching Man Wai Source Type: research

The gene regulatory basis of genetic compensation during neural crest induction
by Christopher M. Dooley, Neha Wali, Ian M. Sealy, Richard J. White, Derek L. Stemple, John E. Collins, Elisabeth M. Busch-Nentwich The neural crest (NC) is a vertebrate-specific cell type that contributes to a wide range of different tissues across all three germ layers. The gene regulatory network (GRN) responsible for the formation of neural crest is conserved across vertebrates. Central to the induction of the NC GRN areAP-2 andSoxE transcription factors. NC induction robustness is ensured through the ability of some of these transcription factors to compensate loss of function of gene family members. However the gene...
Source: PLoS Genetics - June 14, 2019 Category: Genetics & Stem Cells Authors: Christopher M. Dooley Source Type: research

Profound analgesia is associated with a truncated peptide resulting from tissue specific alternative splicing of DRG CA8-204 regulated by an exon-level < i > cis < /i > -eQTL
In this report, we identify an exon-levelcis-eQTL (rs6471859) that regulates human DRG CA8 alternative splicing, producing a truncated 1,697bp transcript (e.g., CA8-204). Our functional genomic studies show the “G” allele at rs6471859 produces a cryptic 3’UTR splice site regulating expression of CA8-204. We developed constructs to study the expression and function of the naturally occurring CA8-204G transcript (G allele at rs6471859), CA8-204C (C allele at rs6471859 reversion mutation) and CA8-201 (full length transcript). CA8-204G transcript expression occurred predominantly in non-neuronal cells (HEK293...
Source: PLoS Genetics - June 14, 2019 Category: Genetics & Stem Cells Authors: Udita Upadhyay Source Type: research

Risk of spontaneous preterm birth and fetal growth associates with fetal < i > SLIT2 < /i >
by Heli Tiensuu, Antti M. Haapalainen, Minna K. Karjalainen, Anu Pasanen, Johanna M. Huusko, Riitta Marttila, Marja Ojaniemi, Louis J. Muglia, Mikko Hallman, Mika R ämet Spontaneous preterm birth (SPTB) is the leading cause of neonatal death and morbidity worldwide. Both maternal and fetal genetic factors likely contribute to SPTB. We performed a genome-wide association study (GWAS) on a population of Finnish origin that included 247 infants with SPTB (gestational age [GA] (Source: PLoS Genetics)
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: Heli Tiensuu Source Type: research

Essential long-range action of Wingless/Wnt in adult intestinal compartmentalization
by Ai Tian, Deepesh Duwadi, Hassina Benchabane, Yashi Ahmed Signal transduction activated by Wingless/Wnt ligands directs cell proliferation and fate specification in metazoans, and its overactivation underlies the development of the vast majority of colorectal cancers. In the conventional model, the secretion and movement of Wingless to cells distant from its source of synthesis are essential for long-range signaling in tissue patterning. However, this model was upended recently by an unanticipated finding: replacement of wild-type Drosophila Wingless with a membrane-tethered form produced viable adults with largely norm...
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: Ai Tian Source Type: research

Diffusion and function of Wnt ligands
by Richard A. Stewart, Aravinda-Bharathi Ramakrishnan, Ken M. Cadigan (Source: PLoS Genetics)
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: Richard A. Stewart Source Type: research

Peptidergic signaling from clock neurons regulates reproductive dormancy in < i > Drosophila melanogaster < /i >
by D óra Nagy, Paola Cusumano, Gabriele Andreatta, Ane Martin Anduaga, Christiane Hermann-Luibl, Nils Reinhard, João Gesto, Christian Wegener, Gabriella Mazzotta, Ezio Rosato, Charalambos P. Kyriacou, Charlotte Helfrich-Förster, Rodolfo Costa With the approach of winter, many insects switch to an alternative protective developmental program called diapause.Drosophila melanogaster females overwinter as adults by inducing a reproductive arrest that is characterized by inhibition of ovarian development at previtellogenic stages. The insulin producing cells (IPCs) are key regulators of this process, since t...
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: D óra Nagy Source Type: research

Genome-wide association study of multisite chronic pain in UK Biobank
by Keira J. A. Johnston, Mark J. Adams, Barbara I. Nicholl, Joey Ward, Rona J. Strawbridge, Amy Ferguson, Andrew M. McIntosh, Mark E. S. Bailey, Daniel J. Smith Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype ‘chronic pain grade’, have been shown previously to be complex heritable traits with a polygen ic component. Additional pain-related phenotypes capturing aspects of an individual’s overall sensitivity to experiencing and reporting chronic pain have a...
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: Keira J. A. Johnston Source Type: research

Exploring various polygenic risk scores for skin cancer in the phenomes of the Michigan genomics initiative and the UK Biobank with a visual catalog: < i > PRSWeb < /i >
This study was conducted using data from 30,702 unrelated, genotyped patients of recent European descent from the Michigan Genomics Initiative (MGI), a longitudinal biorepository effort within Michigan Medicine. We examine the three most common skin cancer subtypes in the USA: basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma. Using these PRS for various skin cancer subtypes, we conduct a phenome-wide association study (PheWAS) within the MGI data to evaluate PRS associations with secondary traits. PheWAS results are then replicated using population-based UK Biobank data and compared across various PRS ...
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: Lars G. Fritsche Source Type: research

A new identified suppressor of Cdc7p/SepH kinase, PomA, regulates fungal asexual reproduction via affecting phosphorylation of MAPK-HogA
In this study, a SepH suppressor–PomA in the filamentous fungusA.nidulans is identified as a negative regulator of septation and conidiation such that thepomA mutant is able to cure defects ofsepH1 in septation and conidiation and overexpression ofpomA remarkably suppresses septation. Under the normal cultural condition, SepH positively regulates the phosphorylation of MAPK-HogA, while PomA reversely affects this process. In the absence of PbsB (MAPKK, a putative upstream member of HogA), PomA and SepH are unable to affect the phosphorylation level of HogA. Under the osmostress condition, the induced phosphorylated H...
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: Xiaogang Zhou Source Type: research

A key role for sex chromosomes in the regulation of parthenogenesis in the brown alga < i > Ectocarpus < /i >
by Laure Mignerot, Komlan Avia, Remy Luthringer, Agnieszka P. Lipinska, Akira F. Peters, J. Mark Cock, Susana M. Coelho Although evolutionary transitions from sexual to asexual reproduction are frequent in eukaryotes, the genetic bases of these shifts remain largely elusive. Here, we used classic quantitative trait analysis, combined with genomic and transcriptomic information to dissect the genetic basis of asexua l, parthenogenetic reproduction in the brown algaEctocarpus. We found that parthenogenesis is controlled by the sex locus, together with two additional autosomal loci, highlighting the key role of the sex chrom...
Source: PLoS Genetics - June 13, 2019 Category: Genetics & Stem Cells Authors: Laure Mignerot Source Type: research

Genomic variation predicts adaptive evolutionary responses better than population bottleneck history
by Michael Ørsted, Ary Anthony Hoffmann, Elsa Sverrisdóttir, Kåre Lehmann Nielsen, Torsten Nygaard Kristensen The relationship between population size, inbreeding, loss of genetic variation and evolutionary potential of fitness traits is still unresolved, and large-scale empirical studies testing theoretical expectations are surprisingly scarce. Here we present a highly replicated experimental evolution s etup with 120 lines ofDrosophila melanogaster having experienced inbreeding caused by low population size for a variable number of generations. Genetic variation in inbred lines and in outbred control...
Source: PLoS Genetics - June 12, 2019 Category: Genetics & Stem Cells Authors: Michael Ørsted Source Type: research

Essential gene deletions producing gigantic bacteria
by Jeannie Bailey, Julie Cass, Joe Gasper, Ngoc-Diep Ngo, Paul Wiggins, Colin Manoil To characterize the consequences of eliminating essential functions needed for peptidoglycan synthesis, we generated deletion mutations ofAcinetobacter baylyi by natural transformation and visualized the resulting microcolonies of dead cells. We found that loss of genes required for peptidoglycan precursor synthesis or polymerization led to the formation of polymorphic giant cells with diameters that could exceed ten times normal. Treatment with antibiotics targeting early or late steps of peptidoglycan synthesis also produced giant cells...
Source: PLoS Genetics - June 10, 2019 Category: Genetics & Stem Cells Authors: Jeannie Bailey Source Type: research

Models of archaic admixture and recent history from two-locus statistics
by Aaron P. Ragsdale, Simon Gravel We learn about population history and underlying evolutionary biology through patterns of genetic polymorphism. Many approaches to reconstruct evolutionary histories focus on a limited number of informative statistics describing distributions of allele frequencies or patterns of linkage disequilib rium. We show that many commonly used statistics are part of a broad family of two-locus moments whose expectation can be computed jointly and rapidly under a wide range of scenarios, including complex multi-population demographies with continuous migration and admixture events. A full inspecti...
Source: PLoS Genetics - June 10, 2019 Category: Genetics & Stem Cells Authors: Aaron P. Ragsdale Source Type: research

Cyclophilin B control of lysine post-translational modifications of skin type I collagen
by Masahiko Terajima, Yuki Taga, Wayne A. Cabral, Ying Liu, Masako Nagasawa, Noriko Sumida, Yukako Kayashima, Prashant Chandrasekaran, Lin Han, Nobuyo Maeda, Irina Perdivara, Shunji Hattori, Joan C. Marini, Mitsuo Yamauchi Covalent intermolecular cross-linking of collagen is essential for tissue stability. Recent studies have demonstrated that cyclophilin B (CypB), an endoplasmic reticulum (ER)-resident peptidyl-prolyl cis-trans isomerase, modulates lysine (Lys) hydroxylation of type I collagen impacting cross-linki ng chemistry. However, the extent of modulation, the molecular mechanism and the functional outcome in tiss...
Source: PLoS Genetics - June 7, 2019 Category: Genetics & Stem Cells Authors: Masahiko Terajima Source Type: research

Asymmetrical localization of Nup107-160 subcomplex components within the nuclear pore complex in fission yeast
by Haruhiko Asakawa, Tomoko Kojidani, Hui-Ju Yang, Chizuru Ohtsuki, Hiroko Osakada, Atsushi Matsuda, Masaaki Iwamoto, Yuji Chikashige, Koji Nagao, Chikashi Obuse, Yasushi Hiraoka, Tokuko Haraguchi The nuclear pore complex (NPC) forms a gateway for nucleocytoplasmic transport. The outer ring protein complex of the NPC (the Nup107-160 subcomplex in humans) is a key component for building the NPC. Nup107-160 subcomplexes are believed to be symmetrically localized on the nuclear and cytoplasmic sides of the NPC. However, inS.pombe immunoelectron and fluorescence microscopic analyses revealed that the homologous components of ...
Source: PLoS Genetics - June 6, 2019 Category: Genetics & Stem Cells Authors: Haruhiko Asakawa Source Type: research

Mitochondrial fusion is required for regulation of mitochondrial DNA replication
by Eduardo Silva Ramos, Elisa Motori, Christian Br üser, Inge Kühl, Assa Yeroslaviz, Benedetta Ruzzenente, Johanna H. K. Kauppila, Jakob D. Busch, Kjell Hultenby, Bianca H. Habermann, Stefan Jakobs, Nils-Göran Larsson, Arnaud Mourier Mitochondrial dynamics is an essential physiological process controlling mitochondrial content mixing and mobility to ensure proper function and localization of mitochondria at intracellular sites of high-energy demand. Intriguingly, for yet unknown reasons, severe impairment of mitochondrial fusi on drastically affects mtDNA copy number. To decipher the link between mitochondr...
Source: PLoS Genetics - June 6, 2019 Category: Genetics & Stem Cells Authors: Eduardo Silva Ramos Source Type: research

Reshaping membranes to build mitochondrial DNA
by David Pla-Martin, Rudolf J. Wiesner (Source: PLoS Genetics)
Source: PLoS Genetics - June 6, 2019 Category: Genetics & Stem Cells Authors: David Pla-Martin Source Type: research

A mutation in the endonuclease domain of mouse MLH3 reveals novel roles for MutL γ during crossover formation in meiotic prophase I
by Melissa Toledo, Xianfei Sun, Miguel A. Brie ño-Enríquez, Vandana Raghavan, Stephen Gray, Jeffrey Pea, Carolyn R. Milano, Anita Venkatesh, Lekha Patel, Peter L. Borst, Eric Alani, Paula E. Cohen During meiotic prophase I, double-strand breaks (DSBs) initiate homologous recombination leading to non-crossovers (NCOs) and crossovers (COs). In mouse, 10% of DSBs are designated to become COs, primarily through a pathway dependent on the MLH1-MLH3 heterodimer (MutLγ). Mlh3 contains an endonucl ease domain that is critical for resolving COs in yeast. We generated a mouse (Mlh3DN/DN) harboring a mutation wit...
Source: PLoS Genetics - June 6, 2019 Category: Genetics & Stem Cells Authors: Melissa Toledo Source Type: research

Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease
by Carles Vilari ño-Güell, Alexander Zimprich, Filippo Martinelli-Boneschi, Bruno Herculano, Zhe Wang, Fuencisla Matesanz, Elena Urcelay, Koen Vandenbroeck, Laura Leyva, Denis Gris, Charbel Massaad, Jacqueline A. Quandt, Anthony L. Traboulsee, Mary Encarnacion, Cecily Q. Bernales, Jordan Follett, Irene M. Yee, Mar ia G. Criscuoli, Angela Deutschländer, Eva M. Reinthaler, Tobias Zrzavy, Elisabetta Mascia, Andrea Zauli, Federica Esposito, Antonio Alcina, Guillermo Izquierdo, Laura Espino-Paisán, Jorge Mena, Alfredo Antigüedad, Patricia Urbaneja-Romero, Jesús Ortega-Pinazo, Weihong Song, A....
Source: PLoS Genetics - June 6, 2019 Category: Genetics & Stem Cells Authors: Carles Vilari ño-Güell Source Type: research

Sister centromere fusion during meiosis I depends on maintaining cohesins and destabilizing microtubule attachments
by Lin-Ing Wang, Arunika Das, Kim S. McKim Sister centromere fusion is a process unique to meiosis that promotes co-orientation of the sister kinetochores, ensuring they attach to microtubules from the same pole during metaphase I. We have found that the kinetochore protein SPC105R/KNL1 and Protein Phosphatase 1 (PP1-87B) regulate sister c entromere fusion inDrosophila oocytes. The analysis of these two proteins, however, has shown that two independent mechanisms maintain sister centromere fusion. Maintenance of sister centromere fusion by SPC105R depends on Separase, suggesting cohesin proteins must be maintained at the ...
Source: PLoS Genetics - May 31, 2019 Category: Genetics & Stem Cells Authors: Lin-Ing Wang Source Type: research

Enhancing face validity of mouse models of Alzheimer ’s disease with natural genetic variation
by Kristen D. Onos, Asli Uyar, Kelly J. Keezer, Harriet M. Jackson, Christoph Preuss, Casey J. Acklin, Rita O ’Rourke, Rebecca Buchanan, Travis L. Cossette, Stacey J. Sukoff Rizzo, Ileana Soto, Gregory W. Carter, Gareth R. Howell Classical laboratory strains show limited genetic diversity and do not harness natural genetic variation. Mouse models relevant to Alzheimer’s disease (AD) have largely been developed using these classical laboratory strains, such as C57BL/6J (B6), and this has likely contributed to the failure of translation of findings from mice to the clinic. Therefore, here we test the potential f...
Source: PLoS Genetics - May 31, 2019 Category: Genetics & Stem Cells Authors: Kristen D. Onos Source Type: research

CREB-B acts as a key mediator of NPF/NO pathway involved in phase-related locomotor plasticity in locusts
by Li Hou, Beibei Li, Ding Ding, Le Kang, Xianhui Wang Gene expression changes in neural systems are essential for environment-induced behavioral plasticity in animals; however, neuronal signaling pathways mediating the effect of external stimuli on transcriptional changes are largely unknown. Recently, we have demonstrated that the neuropeptide F (NP F)/nitric oxide (NO) signaling pathway plays a regulatory role in phase-related locomotor plasticity in the migratory locust,Locusta migratoria. Here, we report that a conserved transcription factor, cAMP response element-binding protein B (CREB-B), is a key mediator involve...
Source: PLoS Genetics - May 31, 2019 Category: Genetics & Stem Cells Authors: Li Hou Source Type: research

A novel rice grain size gene < i > OsSNB < /i > was identified by genome-wide association study in natural population
by Xiaosong Ma, Fangjun Feng, Yu Zhang, Ibrahim Eid Elesawi, Kai Xu, Tianfei Li, Hanwei Mei, Hongyan Liu, Ningning Gao, Chunli Chen, Lijun Luo, Shunwu Yu Increasing agricultural productivity is one of the most important goals of plant science research and imperative to meet the needs of a rapidly growing population. Rice (Oryza sativa L.) is one of the most important staple crops worldwide. Grain size is both a major determinant of grain yield in rice and a target trait for domestication and artificial breeding. Here, a genome-wide association study of grain length and grain width was performed using 996,722 SNP markers i...
Source: PLoS Genetics - May 31, 2019 Category: Genetics & Stem Cells Authors: Xiaosong Ma Source Type: research

Quorum sensing and stress-activated MAPK signaling repress yeast to hypha transition in the fission yeast < i > Schizosaccharomyces japonicus < /i >
by Elisa G ómez-Gil, Alejandro Franco, Marisa Madrid, Beatriz Vázquez-Marín, Mariano Gacto, Jesualdo Fernández-Breis, Jero Vicente-Soler, Teresa Soto, José Cansado Quorum sensing (QS), a mechanism of microbial communication dependent on cell density, governs developmental decisions in many bacteria and in some pathogenic and non-pathogenic fungi including yeasts. In these simple eukaryotes this response is mediated by the release into the growth medium of qu orum-sensing molecules (QSMs) whose concentration increases proportionally to the population density. To date the occurrence of QS ...
Source: PLoS Genetics - May 31, 2019 Category: Genetics & Stem Cells Authors: Elisa G ómez-Gil Source Type: research

No “doom” in chicken domestication?
by Mirte Bosse (Source: PLoS Genetics)
Source: PLoS Genetics - May 30, 2019 Category: Genetics & Stem Cells Authors: Mirte Bosse Source Type: research

Correction: Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population
by Manuel A. Rivas, Brandon E. Avila, Jukka Koskela, Hailiang Huang, Christine Stevens, Matti Pirinen, Talin Haritunians, Benjamin M. Neale, Mitja Kurki, Andrea Ganna, Daniel Graham, Benjamin Glaser, Inga Peter, Gil Atzmon, Nir Barzilai, Adam P. Levine, Elena Schiff, Nikolas Pontikos, Ben Weisburd, Monkol Lek, Konrad J. Karczewski, Jonathan Bloom, Eric V. Minikel, Britt-Sabina Petersen, Laurent Beaugerie, Philippe Seksik, Jacques Cosnes, Stefan Schreiber, Bernd Bokemeyer, Johannes Bethge, International IBD Genetics Consortium , NIDDK IBD Genetics Consortium , T2D-GENES Consortium , Graham Heap, Tariq Ahmad, Vincent Plagnol...
Source: PLoS Genetics - May 30, 2019 Category: Genetics & Stem Cells Authors: Manuel A. Rivas Source Type: research

Correction: Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures
by The PLOS Genetics Staff (Source: PLoS Genetics)
Source: PLoS Genetics - May 29, 2019 Category: Genetics & Stem Cells Authors: The PLOS Genetics Staff Source Type: research

Identification and validation of genetic variants predictive of gait in standardbred horses
by Annette M. McCoy, Samantha K. Beeson, Carl-Johan Rubin, Leif Andersson, Paul Caputo, Sigrid Lykkjen, Alison Moore, Richard J. Piercy, James R. Mickelson, Molly E. McCue Several horse breeds have been specifically selected for the ability to exhibit alternative patterns of locomotion, or gaits. A premature stop codon in the geneDMRT3 is permissive for “gaitedness” across breeds. However, this mutation is nearly fixed in both American Standardbred trotters and pacers, which perform a diagonal and lateral gait, respectively, during harness racing. This suggests that modifying alleles must influence the preferr...
Source: PLoS Genetics - May 28, 2019 Category: Genetics & Stem Cells Authors: Annette M. McCoy Source Type: research

Genetic analyses led to the discovery of a super-active mutant of the RNA polymerase I
by Tommy Darri ère, Michael Pilsl, Marie-Kerguelen Sarthou, Adrien Chauvier, Titouan Genty, Sylvain Audibert, Christophe Dez, Isabelle Léger-Silvestre, Christophe Normand, Anthony K. Henras, Marta Kwapisz, Olga Calvo, Carlos Fernández-Tornero, Herbert Tschochner, Olivier Gadal Most transcriptional activity of exponentially growing cells is carried out by the RNA Polymerase I (Pol I), which produces a ribosomal RNA (rRNA) precursor. In budding yeast, Pol I is a multimeric enzyme with 14 subunits. Among them, Rpa49 forms with Rpa34 a Pol I-specific heterodimer (homologous to PAF53/CAST heterodimer in hu...
Source: PLoS Genetics - May 28, 2019 Category: Genetics & Stem Cells Authors: Tommy Darri ère Source Type: research

MNM and SNM maintain but do not establish achiasmate homolog conjunction during < i > Drosophila < /i > male meiosis
by Michael Shoujie Sun, Joe Weber, Ariane C. Blattner, Soumya Chaurasia, Christian F. Lehner The first meiotic division reduces genome ploidy. This requires pairing of homologous chromosomes into bivalents that can be bi-oriented within the spindle during prometaphase I. Thereafter, pairing is abolished during late metaphase I, and univalents are segregated apart onto opposite spindle pol es during anaphase I. In contrast to canonical meiosis, homologous chromosome pairing does not include the formation of a synaptonemal complex and of cross-overs in spermatocytes ofDrosophila melanogaster. The alternative pairing mode in...
Source: PLoS Genetics - May 28, 2019 Category: Genetics & Stem Cells Authors: Michael Shoujie Sun Source Type: research

A statistical model for reference-free inference of archaic local ancestry
We present a statistical method that combines diverse population genetic summary statistics to infer archaic local ancestry without access to an archaic reference genome. We validate the accuracy and robustness of our method in simulations. When applied to genomes of European individuals, our method recovers segments that are substantially enriched for Neanderthal ancestry, even though our method did not have access to any Neanderthal reference genomes. (Source: PLoS Genetics)
Source: PLoS Genetics - May 28, 2019 Category: Genetics & Stem Cells Authors: Arun Durvasula Source Type: research

Aicardi-Gouti ères syndrome gene < i > Rnaseh2c < /i > is a metastasis susceptibility gene in breast cancer
by Sarah K. Deasy, Ryo Uehara, Suman K. Vodnala, Howard H. Yang, Randall A. Dass, Ying Hu, Maxwell P. Lee, Robert J. Crouch, Kent W. Hunter Breast cancer is the second leading cause of cancer-related deaths in the United States, with the majority of these deaths due to metastatic lesions rather than the primary tumor. Thus, a better understanding of the etiology of metastatic disease is crucial for improving survival. Using a haplotyp e mapping strategy in mouse and shRNA-mediated gene knockdown, we identifiedRnaseh2c, a scaffolding protein of the heterotrimeric RNase H2 endoribonuclease complex, as a novel metastasis sus...
Source: PLoS Genetics - May 24, 2019 Category: Genetics & Stem Cells Authors: Sarah K. Deasy Source Type: research

Biallelic < i > HEPHL1 < /i > variants impair ferroxidase activity and cause an abnormal hair phenotype
by Prashant Sharma, Marie Reichert, Yan Lu, Thomas C. Markello, David R. Adams, Peter J. Steinbach, Brie K. Fuqua, Xenia Parisi, Stephen G. Kaler, Christopher D. Vulpe, Gregory J. Anderson, William A. Gahl, May Christine V. Malicdan Maintenance of the correct redox status of iron is functionally important for critical biological processes. Multicopper ferroxidases play an important role in oxidizing ferrous iron, released from the cells, into ferric iron, which is subsequently distributed by transferrin. Two well-characterize d ferroxidases, ceruloplasmin (CP) and hephaestin (HEPH) facilitate this reaction in different ti...
Source: PLoS Genetics - May 24, 2019 Category: Genetics & Stem Cells Authors: Prashant Sharma Source Type: research

Autophagy of germ-granule components, PGL-1 and PGL-3, contributes to DNA damage-induced germ cell apoptosis in < i > C < /i > . < i > elegans < /i >
by Hyemin Min, Yong-Uk Lee, Yhong-Hee Shim, Ichiro Kawasaki Germ granules, termed P granules in nematodeC.elegans, are the germline-specific cytoplasmic structures widely observed from worms to humans. P granules are known to have critical functions for postembryonic germline development likely through regulating RNA metabolism. They are localized at the perinuclear region of germ cells during most of the developmental stages. However, the biological significance of this specific localization remains elusive. PGL-1 and PGL-3, the defining components of P granules, were shown to be lost from the perinuclear region prior to...
Source: PLoS Genetics - May 24, 2019 Category: Genetics & Stem Cells Authors: Hyemin Min Source Type: research

< i > Drosophila < /i > ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle
by Woongchang Yoon, Sun-Hong Hwang, Sang-Hee Lee, Jongkyeong Chung The function of AarF domain-containing kinase 1 (ADCK1) has not been thoroughly revealed. Here we identified that ADCK1 utilizes YME1-like 1 ATPase (YME1L1) to control optic atrophy 1 (OPA1) and inner membrane mitochondrial protein (IMMT) in regulating mitochondrial dynamics and cristae structure. We firstly observed that a serious developmental impairment occurred inDrosophila ADCK1 (dADCK1) deletion mutant, resulting in premature death before adulthood. By using temperature sensitive ubiquitously expression drivertub-Gal80ts/tub-Gal4 or muscle-specific e...
Source: PLoS Genetics - May 24, 2019 Category: Genetics & Stem Cells Authors: Woongchang Yoon Source Type: research

Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development
In this study,Gata4 haploinsufficiency in mice was found to result in OFT defects including double outlet right ventricle (DORV) and ventricular septum defects (VSDs). Gata4 was shown to be required for Hedgehog (Hh)-receiving progenitors within the second heart field (SHF) for normal OFT alignment. Restored cell proliferation in the SHF by knocking-down Pten failed to rescue OFT defects, suggesting that additional cell events under Gata4 regulation is important. SHF Hh-receiving cells failed to migrate properly into the proximal OFT cushion, which is associated with abnormal EMT and cell proliferation in Gata4 haploinsuff...
Source: PLoS Genetics - May 23, 2019 Category: Genetics & Stem Cells Authors: Jielin Liu Source Type: research

Breaking the Y
by Guillaume Holzer, Wolfram Antonin (Source: PLoS Genetics)
Source: PLoS Genetics - May 23, 2019 Category: Genetics & Stem Cells Authors: Guillaume Holzer Source Type: research

Stop-codon read-through arises largely from molecular errors and is generally nonadaptive
by Chuan Li, Jianzhi Zhang Stop-codon read-through refers to the phenomenon that a ribosome goes past the stop codon and continues translating into the otherwise untranslated region (UTR) of a transcript. Recent ribosome-profiling experiments in eukaryotes uncovered widespread stop-codon read-through that also varies among tissues, prompting the adaptive hypothesis that stop-codon read-through is an important, regulated mechanism for generating proteome diversity. Here we propose and test a competing hypothesis that stop-codon read-through arises mostly from molecular errors and is largely nonadaptive. The error hypot hes...
Source: PLoS Genetics - May 23, 2019 Category: Genetics & Stem Cells Authors: Chuan Li Source Type: research

Metabolites of lactic acid bacteria present in fermented foods are highly potent agonists of human hydroxycarboxylic acid receptor 3
We report the discovery of the interaction of D-phenyllactic acid (D-PLA) and the human host through highly potent activation of HCA3. D-PLA is an anti-bacterial metabolite found in high concentrations in LAB-fermented food such as Sauerkraut. We demonstrate that D-PLA from such alimentary sources is well absorbed from the human gut leading to high plasma and urine levels and triggers pertussis toxin-sensitive migration of primary human monocytes in an HCA3-dependent manner. We provide evolutionary, analytical and functional evidence supporting the hypothesis that HCA3 was consolidated in hominids as a new signaling system...
Source: PLoS Genetics - May 23, 2019 Category: Genetics & Stem Cells Authors: Anna Peters Source Type: research

< i > De novo < /i > gene birth
by Stephen Branden Van Oss, Anne-Ruxandra Carvunis (Source: PLoS Genetics)
Source: PLoS Genetics - May 23, 2019 Category: Genetics & Stem Cells Authors: Stephen Branden Van Oss Source Type: research

An Arabidopsis FANCJ helicase homologue is required for DNA crosslink repair and rDNA repeat stability
by Annika Dorn, Laura Feller, Dominique Castri, Sarah R öhrig, Janina Enderle, Natalie J. Herrmann, Astrid Block-Schmidt, Oliver Trapp, Laura Köhler, Holger Puchta Proteins of the Fanconi Anemia (FA) complementation group are required for crosslink (CL) repair in humans and their loss leads to severe pathological phenotypes. Here we characterize a homolog of the Fe-S cluster helicase FANCJ in the model plant Arabidopsis, AtFANCJB, and show that it is involve d in interstrand CL repair. It acts at a presumably early step in concert with the nuclease FAN1 but independently of the nuclease AtMUS81, and is epistatic...
Source: PLoS Genetics - May 23, 2019 Category: Genetics & Stem Cells Authors: Annika Dorn Source Type: research

CBX2 is required to stabilize the testis pathway by repressing Wnt signaling
by S. Alexandra Garcia-Moreno, Yi-Tzu Lin, Christopher R. Futtner, Isabella M. Salamone, Blanche Capel, Danielle M. Maatouk XX and XY fetal gonads are initially bipotential, poised between the ovary and testis fate. Multiple lines of evidence suggest that commitment to testis fate requires the repression of genes associated with ovary fate. It was previously shown that loss of CBX2, the subunit of the Polycomb Repressi ve Complex 1 (PRC1) that binds H3K27me3 and mediates silencing, leads to ovary development in XY mice and humans. While it had been proposed that CBX2 is an activator of the testis-determining geneSry, we i...
Source: PLoS Genetics - May 22, 2019 Category: Genetics & Stem Cells Authors: S. Alexandra Garcia-Moreno Source Type: research

The dPix-Git complex is essential to coordinate epithelial morphogenesis and regulate myosin during < i > Drosophila < /i > egg chamber development
by Lucas G. Dent, Samuel A. Manning, Benjamin Kroeger, Audrey M. Williams, Abdul Jabbar Saiful Hilmi, Luke Crea, Shu Kondo, Sally Horne-Badovinac, Kieran F. Harvey How biochemical and mechanical information are integrated during tissue development is a central question in morphogenesis. In many biological systems, the PIX-GIT complex localises to focal adhesions and integrates both physical and chemical information. We usedDrosophila melanogaster egg chamber formation to study the function of PIX and GIT orthologues (dPix and Git, respectively), and discovered a central role for this complex in controlling myosin activity...
Source: PLoS Genetics - May 22, 2019 Category: Genetics & Stem Cells Authors: Lucas G. Dent Source Type: research

The subunit of RNA N6-methyladenosine methyltransferase OsFIP regulates early degeneration of microspores in rice
This study also provides evidence for the different functions of the m6A RNA methyltransferase complex between rice and Arabidopsis. (Source: PLoS Genetics)
Source: PLoS Genetics - May 22, 2019 Category: Genetics & Stem Cells Authors: Fan Zhang Source Type: research

Genetics of cocaine and methamphetamine consumption and preference in < i > Drosophila melanogaster < /i >
by Chad A. Highfill, Brandon M. Baker, Stephenie D. Stevens, Robert R. H. Anholt, Trudy F. C. Mackay Illicit use of psychostimulants, such as cocaine and methamphetamine, constitutes a significant public health problem. Whereas neural mechanisms that mediate the effects of these drugs are well-characterized, genetic factors that account for individual variation in susceptibility to substance abus e and addiction remain largely unknown.Drosophila melanogaster can serve as a translational model for studies on substance abuse, since flies have a dopamine transporter that can bind cocaine and methamphetamine, and exposure to ...
Source: PLoS Genetics - May 20, 2019 Category: Genetics & Stem Cells Authors: Chad A. Highfill Source Type: research