The Art and Design of Genetic Screens: Mouse
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Meiotic Cohesin and Variants Associated with Human Reproductive Aging and Disease
fcell-09-710033 July 27, 2021 Time: 16:27 # 1 REVIEW published: 02 August 2021 doi: 10.3389/fcell.2021.710033 Meiotic Cohesin and Variants Associated With Human Reproductive Aging and Disease Rachel Beverley1, Meredith L. Snook1 and Miguel Angel Brieño-Enríquez2* 1 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States, 2 Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, United States Successful human reproduction relies on the well-orchestrated development of competent gametes through the process of meiosis. The loading of cohesin, a multi- protein complex, is a key event in the initiation of mammalian meiosis. Establishment of sister chromatid cohesion via cohesin rings is essential for ensuring homologous recombination-mediated DNA repair and future proper chromosome segregation. Cohesin proteins loaded during female fetal life are not replenished over time, and therefore are a potential etiology of age-related aneuploidy in oocytes resulting in Edited by: decreased fecundity and increased infertility and miscarriage rates with advancing Karen Schindler, Rutgers, The State University maternal age. Herein, we provide a brief overview of meiotic cohesin and summarize of New Jersey, United States the human genetic studies which have identified genetic variants of cohesin proteins and Reviewed by: the associated reproductive phenotypes -
Atrec8 and Atscc3 Are Essential to the Monopolar Orientation of the Kinetochores During Meiosis
Research Article 4621 AtREC8 and AtSCC3 are essential to the monopolar orientation of the kinetochores during meiosis Liudmila Chelysheva, Stéphanie Diallo*, Daniel Vezon, Ghislaine Gendrot, Nathalie Vrielynck, Katia Belcram, Nathalie Rocques, Angustias Márquez-Lema‡, Anuj M. Bhatt§, Christine Horlow, Raphaël Mercier, Christine Mézard and Mathilde Grelon¶ Institut Jean-Pierre Bourgin, Station de Génétique et d’Amélioration des Plantes, INRA de Versailles, Route de Saint-Cyr, 78026 Versailles CEDEX, France *Present address: Laboratoire de Microbiologie du Froid UPRES 2123, 55 Rue Saint-Germain, 27000 Evreux, France ‡Present address: Instituto de Agricultura Sostenible (CSIC), Apartado 4084, E-14080, Córdoba, Spain §Present address: Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK ¶Author for correspondence (e-mail: [email protected]) Accepted 13 July 2005 Journal of Cell Science 118, 4621-4632 Published by The Company of Biologists 2005 doi:10.1242/jcs.02583 Summary The success of the first meiotic division relies (among other in meiotic nuclei as early as interphase, and bound to the factors) on the formation of bivalents between homologous chromosome axis from early leptotene through to anaphase chromosomes, the monopolar orientation of the sister I. We show here that both AtREC8 and AtSCC3 are kinetochores at metaphase I and the maintenance of necessary not only to maintain centromere cohesion at centromeric cohesion until the onset of anaphase II. The anaphase I, but also for the monopolar orientation of the meiotic cohesin subunit, Rec8 has been reported to be one kinetochores during the first meiotic division. We also of the key players in these processes, but its precise role in found that AtREC8 is involved in chromosome axis kinetochore orientation is still under debate. -
Mouse Germ Line Mutations Due to Retrotransposon Insertions Liane Gagnier1, Victoria P
Gagnier et al. Mobile DNA (2019) 10:15 https://doi.org/10.1186/s13100-019-0157-4 REVIEW Open Access Mouse germ line mutations due to retrotransposon insertions Liane Gagnier1, Victoria P. Belancio2 and Dixie L. Mager1* Abstract Transposable element (TE) insertions are responsible for a significant fraction of spontaneous germ line mutations reported in inbred mouse strains. This major contribution of TEs to the mutational landscape in mouse contrasts with the situation in human, where their relative contribution as germ line insertional mutagens is much lower. In this focussed review, we provide comprehensive lists of TE-induced mouse mutations, discuss the different TE types involved in these insertional mutations and elaborate on particularly interesting cases. We also discuss differences and similarities between the mutational role of TEs in mice and humans. Keywords: Endogenous retroviruses, Long terminal repeats, Long interspersed elements, Short interspersed elements, Germ line mutation, Inbred mice, Insertional mutagenesis, Transcriptional interference Background promoter and polyadenylation motifs and often a splice The mouse and human genomes harbor similar types of donor site [10, 11]. Sequences of full-length ERVs can TEs that have been discussed in many reviews, to which encode gag, pol and sometimes env, although groups of we refer the reader for more in depth and general infor- LTR retrotransposons with little or no retroviral hom- mation [1–9]. In general, both human and mouse con- ology also exist [6–9]. While not the subject of this re- tain ancient families of DNA transposons, none view, ERV LTRs can often act as cellular enhancers or currently active, which comprise 1–3% of these genomes promoters, creating chimeric transcripts with genes, and as well as many families or groups of retrotransposons, have been implicated in other regulatory functions [11– which have caused all the TE insertional mutations in 13]. -
Detailed Review Paper on Retinoid Pathway Signalling
1 1 Detailed Review Paper on Retinoid Pathway Signalling 2 December 2020 3 2 4 Foreword 5 1. Project 4.97 to develop a Detailed Review Paper (DRP) on the Retinoid System 6 was added to the Test Guidelines Programme work plan in 2015. The project was 7 originally proposed by Sweden and the European Commission later joined the project as 8 a co-lead. In 2019, the OECD Secretariat was added to coordinate input from expert 9 consultants. The initial objectives of the project were to: 10 draft a review of the biology of retinoid signalling pathway, 11 describe retinoid-mediated effects on various organ systems, 12 identify relevant retinoid in vitro and ex vivo assays that measure mechanistic 13 effects of chemicals for development, and 14 Identify in vivo endpoints that could be added to existing test guidelines to 15 identify chemical effects on retinoid pathway signalling. 16 2. This DRP is intended to expand the recommendations for the retinoid pathway 17 included in the OECD Detailed Review Paper on the State of the Science on Novel In 18 vitro and In vivo Screening and Testing Methods and Endpoints for Evaluating 19 Endocrine Disruptors (DRP No 178). The retinoid signalling pathway was one of seven 20 endocrine pathways considered to be susceptible to environmental endocrine disruption 21 and for which relevant endpoints could be measured in new or existing OECD Test 22 Guidelines for evaluating endocrine disruption. Due to the complexity of retinoid 23 signalling across multiple organ systems, this effort was foreseen as a multi-step process. -
Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes
G C A T T A C G G C A T genes Article Evolution, Expression and Meiotic Behavior of Genes Involved in Chromosome Segregation of Monotremes Filip Pajpach , Linda Shearwin-Whyatt and Frank Grützner * School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia; fi[email protected] (F.P.); [email protected] (L.S.-W.) * Correspondence: [email protected] Abstract: Chromosome segregation at mitosis and meiosis is a highly dynamic and tightly regulated process that involves a large number of components. Due to the fundamental nature of chromosome segregation, many genes involved in this process are evolutionarily highly conserved, but duplica- tions and functional diversification has occurred in various lineages. In order to better understand the evolution of genes involved in chromosome segregation in mammals, we analyzed some of the key components in the basal mammalian lineage of egg-laying mammals. The chromosome passenger complex is a multiprotein complex central to chromosome segregation during both mitosis and meio- sis. It consists of survivin, borealin, inner centromere protein, and Aurora kinase B or C. We confirm the absence of Aurora kinase C in marsupials and show its absence in both platypus and echidna, which supports the current model of the evolution of Aurora kinases. High expression of AURKBC, an ancestor of AURKB and AURKC present in monotremes, suggests that this gene is performing all necessary meiotic functions in monotremes. Other genes of the chromosome passenger complex complex are present and conserved in monotremes, suggesting that their function has been preserved Citation: Pajpach, F.; in mammals. -
Mice Exposed to N-Ethyl-N-Nitrosourea T
Proc. Nati. Acad. Sci. USA Vol. 89, pp. 7866-7870, September 1992 Genetics Mutational spectrum at the Hprt locus in splenic T cells of B6C3F1 mice exposed to N-ethyl-N-nitrosourea T. R. SKOPEK*tt, V. E. WALKER*, J. E. COCHRANEt, T. R. CRAFTt, AND N. F. CARIELLO* *Department of Pathology and tDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Communicated by Kenneth M. Brinkhous, May 26, 1992 ABSTRACT We have determined the mutational spectrum quences for analysis. DGGE is based on the fact that the of N-ethyl-N-nitrosourea (ENU) in exon 3 of the hypoxanthine electrophoretic mobility of a DNA molecule in a polyacryl- guanine) phosphoribosyltransferase gene (Hprt) in splenic T amide gel is considerably reduced as the molecule becomes cells following in vivo exposure ofmale B6C3F1 mice (5-7 weeks partially melted (denatured). Mismatched heteroduplexes old) to ENU. Hpir mutants were isolated by culturing splenic formed by annealing wild-type and mutant DNA sequences T cells in microtiter dishes containing medium supplemented are always less stable than the corresponding perfectly base- with interleukin 2, concanavalin A, and 6-thiouanine. DNA paired homoduplexes and consequently melt at a lower was extracted from 6-thoa ne-sistant colonies and ampli- concentration of denaturant. Therefore, any mutant/wild- fied by the polymerase chain reaction (PCR) using primers type heteroduplex will always travel a shorter distance rel- flanking Hprt exon 3. Identification of mutant sequences and ative to wild-type homoduplexes in a gel containing a dient purification of mutant DNA from contaminating wild-type Hprt ofdenaturant. -
Human Pigmentation Genes Under Environmental Selection Richard a Sturm1,* and David L Duffy2
CORE Metadata, citation and similar papers at core.ac.uk Provided by University of Queensland eSpace Sturm and Duffy Genome Biology 2012, 13:248 http://genomebiology.com/2012/13/9/248 revw Ie Human pigmentation genes under environmental selection Richard A Sturm1,* and David L Duffy2 Abstract the iridial melanocytes of the eye [3]. Variations in genes within this pathway are therefore in a position to be Genome-wide association studies and comparative pleiotropic in action, causing skin, hair and eye color to genomics have established major loci and specific become correlated, for example, in Northern European polymorphisms affecting human skin, hair and eye populations with a high frequency of light hair, light skin color. Environmental changes have had an impact and blue eyes or equatorial Africans with dark com plexion, on selected pigmentation genes as populations have dark hair and brown eye color. However, since melanocytes expanded into different regions of the globe. located in these three compartments repre sent indepen dent cellular populations [4] with alternative regulatory or signaling pathways [5], traitspecific variants also occur, Introduction producing assorted phenotypic com binations such as dark Skin, hair and eye color vary dramatically among hair, light skin and blue eyes common in Europeans or the geographically and temporally separated human light hair, dark skin and brown eyes seen in Solomon populations. It has long been speculated that this is due Islanders. Another example of this is the sensitivity of to adaptive changes, but the genetic causes and follicular melanocytes to aging, gradually producing a environmental selective pressures underlying this range silvergray to white hair color, indicating a loss of cells of phenotypic variation have remained largely unknown. -
Expression of Candidate Genes Associated with Obesity in Peripheral White Blood Cells of Mexican Children
Basic research Expression of candidate genes associated with obesity in peripheral white blood cells of Mexican children Marcela Ulloa-Martínez1, Ana I. Burguete-García2, Selvasankar Murugesan1,3, Carlos Hoyo-Vadillo3, Miguel Cruz-Lopez4, Jaime García-Mena1 1Departamento de Genética y Biología Molecular, Centro de Investigación y de Corresponding author: Estudios Avanzados del IPN, México, México Jaime García-Mena PhD 2Dirección de Infecciones Crónicas y Cáncer, CISEI, Instituto Nacional de Salud Pública, Departamento de Genética México, México y Biología Molecular 3Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Centro de Investigación IPN, México, México y de Estudios Avanzados 4Unidad Unidad de Investigación Médica en Bioquímica, Centro Médico Nacional del IPN Siglo XXI, Instituto Mexicano del Seguro Social, México, México Av IPN #2508 Col Zacatenco Submitted: 3 December 2014 07360 México, México Accepted: 4 February 2015 Phone: +52 55 5747-3800 ext. 5328 Arch Med Sci 2016; 12, 5: 968–976 E-mail: [email protected] DOI: 10.5114/aoms.2016.58126 Copyright © 2016 Termedia & Banach Abstract Introduction: Obesity is a chronic, complex, and multifactorial disease, char- acterized by excess body fat. Diverse studies of the human genome have led to the identification of susceptibility genes that contribute to obesity. However, relatively few studies have addressed specifically the association between the level of expression of these genes and obesity. Material and methods: We studied 160 healthy and obese unrelated Mexi- can children aged 6 to 14 years. We measured the transcriptional expression of 20 genes associated with obesity, in addition to the biochemical parame- ters, in peripheral white blood cells. -
Application of CRISPR Genetic Screens to Investigate Neurological Diseases
Application of CRISPR genetic screens to investigate neurological diseases The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation So, Raphaella W.L., et al. "Application of CRISPR genetic screens to investigate neurological diseases." Molecular Neurodegeneration 14 (2019): 41. https://doi.org/10.1186/s13024-019-0343-3 As Published https://doi.org/10.1186/s13024-019-0343-3 Publisher BioMed Central Version Final published version Citable link https://hdl.handle.net/1721.1/126106 Terms of Use Creative Commons Attribution Detailed Terms https://creativecommons.org/licenses/by/4.0/ So et al. Molecular Neurodegeneration (2019) 14:41 https://doi.org/10.1186/s13024-019-0343-3 REVIEW Open Access Application of CRISPR genetic screens to investigate neurological diseases Raphaella W. L. So1,2, Sai Wai Chung1, Heather H. C. Lau1,2, Jeremy J. Watts3, Erin Gaudette1, Zaid A. M. Al-Azzawi1, Jossana Bishay1, Lilian Tsai-Wei Lin1,2, Julia Joung4,5, Xinzhu Wang1,2 and Gerold Schmitt-Ulms1,2* Abstract The adoption of CRISPR-Cas9 technology for functional genetic screens has been a transformative advance. Due to its modular nature, this technology can be customized to address a myriad of questions. To date, pooled, genome- scale studies have uncovered genes responsible for survival, proliferation, drug resistance, viral susceptibility, and many other functions. The technology has even been applied to the functional interrogation of the non-coding genome. However, applications of this technology to neurological diseases remain scarce. This shortfall motivated the assembly of a review that will hopefully help researchers moving in this direction find their footing. -
Human Lectins, Their Carbohydrate Affinities and Where to Find Them
biomolecules Review Human Lectins, Their Carbohydrate Affinities and Where to Review HumanFind Them Lectins, Their Carbohydrate Affinities and Where to FindCláudia ThemD. Raposo 1,*, André B. Canelas 2 and M. Teresa Barros 1 1, 2 1 Cláudia D. Raposo * , Andr1 é LAQVB. Canelas‐Requimte,and Department M. Teresa of Chemistry, Barros NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829‐516 Caparica, Portugal; [email protected] 12 GlanbiaLAQV-Requimte,‐AgriChemWhey, Department Lisheen of Chemistry, Mine, Killoran, NOVA Moyne, School E41 of ScienceR622 Co. and Tipperary, Technology, Ireland; canelas‐ [email protected] NOVA de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2* Correspondence:Glanbia-AgriChemWhey, [email protected]; Lisheen Mine, Tel.: Killoran, +351‐212948550 Moyne, E41 R622 Tipperary, Ireland; [email protected] * Correspondence: [email protected]; Tel.: +351-212948550 Abstract: Lectins are a class of proteins responsible for several biological roles such as cell‐cell in‐ Abstract:teractions,Lectins signaling are pathways, a class of and proteins several responsible innate immune for several responses biological against roles pathogens. such as Since cell-cell lec‐ interactions,tins are able signalingto bind to pathways, carbohydrates, and several they can innate be a immuneviable target responses for targeted against drug pathogens. delivery Since sys‐ lectinstems. In are fact, able several to bind lectins to carbohydrates, were approved they by canFood be and a viable Drug targetAdministration for targeted for drugthat purpose. delivery systems.Information In fact, about several specific lectins carbohydrate were approved recognition by Food by andlectin Drug receptors Administration was gathered for that herein, purpose. plus Informationthe specific organs about specific where those carbohydrate lectins can recognition be found by within lectin the receptors human was body. -
Perspectives
Copyright Ó 2010 by the Genetics Society of America DOI: 10.1534/genetics.109.112938 Perspectives Anecdotal, Historical and Critical Commentaries on Genetics The Impact of Whole Genome Sequencing on Model System Genetics: Get Ready for the Ride Oliver Hobert Columbia University Medical Center, Howard Hughes Medical Institute, New York, New York 10032 ABSTRACT Much of our understanding of how organisms develop and function is derived from the extraordinarily powerful, classic approach of screening for mutant organisms in which a specific biological process is disrupted. Reaping the fruits of such forward genetic screens in metazoan model systems like Drosophila, Caenorhabditis elegans, or zebrafish traditionally involves time-consuming positional cloning strategies that result in the identification of the mutant locus. Whole genome sequencing (WGS) has begun to provide an effective alternative to this approach through direct pinpointing of the molecular lesion in a mutated strain isolated from a genetic screen. Apart from significantly altering the pace and costs of genetic analysis, WGS also provides new perspectives on solving genetic problems that are difficult to tackle with conventional approaches, such as identifying the molecular basis of multigenic and complex traits. ENETIC model systems, from bacteria, yeast, regulatory elements) or chemical mutagens, such as G plants, worms, flies, and fish to mice allow the ethyl methane sulfonate (EMS) or N-ethyl N-nitroso dissection of the genetic basis of virtually any biological urea (ENU), that introduce point mutations or dele- process by isolating mutants obtained through random tions. Point mutation-inducing chemical mutagens are mutagenesis, in which the biological process under in many ways a superior mutagenic agent because their investigation is defective. -
Identification of a Region of Homozygous Deletion on 8P22–23.1 in Medulloblastoma
Oncogene (2002) 21, 1461 ± 1468 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc Identi®cation of a region of homozygous deletion on 8p22 ± 23.1 in medulloblastoma Xiao-lu Yin1, Jesse Chung-sean Pang1 and Ho-keung Ng*,1 1Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China To identify critical tumor suppressor loci that are radiotherapy and chemotherapy, have greatly improved associated with the development of medulloblastoma, the outcomes of patients. In the past 30 years, the 5- we performed a comprehensive genome-wide allelotype year survival rate has increased from 10 to about 50%. analysis in a series of 12 medulloblastomas. Non-random However, long-term survival in children with advanced allelic imbalances were identi®ed on chromosomes 7q disease is only about 30% (Giangaspero et al., 2000; (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and Heideman et al., 1997). Further enhancement of 17q (66.7%). Comparative genomic hybridization analy- survival will rely on a better understanding of the sis con®rmed that allelic imbalances on 8p, 16q and 17p biology of this malignant disease to improve current were due to loss of genetic materials. Finer deletion treatments or to develop novel therapy. mapping in an expanded series of 23 medulloblastomas Non-random loss of genetic material from chromo- localized the common deletion region on 8p to an interval somal loci is a common feature in the development of of 18.14 cM on 8p22 ± 23.2.