Idiopathic Infertility As a Feature of Genome Instability
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Adaptive Tuning of Mutation Rates Allows Fast Response to Lethal Stress In
Manuscript 1 Adaptive tuning of mutation rates allows fast response to lethal stress in 2 Escherichia coli 3 4 a a a a a,b 5 Toon Swings , Bram Van den Bergh , Sander Wuyts , Eline Oeyen , Karin Voordeckers , Kevin J. a,b a,c a a,* 6 Verstrepen , Maarten Fauvart , Natalie Verstraeten , Jan Michiels 7 8 a 9 Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, Kasteelpark Arenberg 20, 10 3001 Leuven, Belgium b 11 VIB Laboratory for Genetics and Genomics, Vlaams Instituut voor Biotechnologie (VIB) Bioincubator 12 Leuven, Gaston Geenslaan 1, 3001 Leuven, Belgium c 13 Smart Systems and Emerging Technologies Unit, imec, Kapeldreef 75, 3001 Leuven, Belgium * 14 To whom correspondence should be addressed: Jan Michiels, Department of Microbial and 2 15 Molecular Systems (M S), Centre of Microbial and Plant Genetics, Kasteelpark Arenberg 20, box 16 2460, 3001 Leuven, Belgium, [email protected], Tel: +32 16 32 96 84 1 Manuscript 17 Abstract 18 19 While specific mutations allow organisms to adapt to stressful environments, most changes in an 20 organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often 21 considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in 22 cellular mutation rates as a response to changes in selective pressure. We show that hypermutation 23 independently evolves when different Escherichia coli cultures adapt to high ethanol stress. 24 Furthermore, hypermutator states are transitory and repeatedly alternate with decreases in mutation 25 rate. Specifically, population mutation rates rise when cells experience higher stress and decline again 26 once cells are adapted. -
Genetic Variation of Genes for Xenobiotic-Metabolizing
Journal of Human Genetics (2009) 54, 440–449 & 2009 The Japan Society of Human Genetics All rights reserved 1434-5161/09 $32.00 www.nature.com/jhg ORIGINAL ARTICLE Genetic variation of genes for xenobiotic-metabolizing enzymes and risk of bronchial asthma: the importance of gene–gene and gene–environment interactions for disease susceptibility Alexey V Polonikov, Vladimir P Ivanov and Maria A Solodilova The aim of our pilot study was to evaluate the contribution of genes for xenobiotic-metabolizing enzymes (XMEs) for the development of bronchial asthma. We have genotyped 25 polymorphic variants of 18 key XME genes in 429 Russians, including 215 asthmatics and 214 healthy controls by a polymerase chain reaction, followed by restriction fragment length polymorphism analyses. We found for the first time significant associations of CYP1B1 V432L (P¼0.045), PON1 Q192R (P¼0.039) and UGT1A6 T181A (P¼0.025) gene polymorphisms with asthma susceptibility. Significant P-values were evaluated through Monte-Carlo simulations. The multifactor-dimensionality reduction method has obtained the best three-locus model for gene–gene interactions between three loci, EPHX1 Y113H, CYP1B1 V432L and CYP2D6 G1934A, in asthma at a maximum cross-validation consistency of 100% (P¼0.05) and a minimum prediction error of 37.8%. We revealed statistically significant gene–environment interactions (XME genotypes–smoking interactions) responsible for asthma susceptibility for seven XME genes. A specific pattern of gametic correlations between alleles of XME genes was found in asthmatics in comparison with healthy individuals. The study results point to the potential relevance of toxicogenomic mechanisms of bronchial asthma in the modern world, and may thereby provide a novel direction in the genetic research of the respiratory disease in the future. -
Pharmacogenetics: a Tool for Identifying Genetic Factors in Drug Dependence and Response to Treatment
RESEARCH REVIEW—PHARMACOGENETICS • 17 Pharmacogenetics: A Tool for Identifying Genetic Factors in Drug Dependence and Response to Treatment harmacogenetics research looks at variations in the human genome and ways in which genetic factors might influence Phow individuals respond to drugs. The authors review basic principles of pharmacogenetics and cite findings from several gene-phenotype studies to illustrate possible associations between genetic variants, drug-related behaviors, and risk for drug dependence. Some gene variants affect responses to one drug; others, to various drugs. Pharmacogenetics can inform medica- tion development and personalized treatment strategies; challenges lie along the pathway to its general use in clinical practice. Margaret Mroziewicz, M.Sc.1 ubstance dependence is a complex psychiatric disorder that develops in Rachel F. Tyndale, Ph.D. 1,2,3 response to a combination of environmental and genetic risk factors and 1 Department of Pharmacology and Toxicology drug-induced effects (Ho et al., 2010). The strong genetic basis of depen- University of Toronto S Toronto, Canada dence is supported by family, adoption, and twin studies, which demonstrate 2Department of Psychiatry substantial heritability, estimated to be about 50 percent (Uhl et al., 2008). The University of Toronto Toronto, Canada evidence suggests that no single variant accounts for a major portion of this risk, 3Centre for Addiction and Mental Health but that variations in many genes each contribute a small amount. Toronto, Canada Pharmacogenetics is the study of the genetic factors that influence drug response and toxicity. In this review, we briefly state the basic principles of pharmacoge- netics and then provide examples of discoveries that demonstrate the impact of genetic variation on drug dependence, drug effects, and drug-induced behaviors. -
Dynamic Mutations on the Move
9789 Mled Genet 1993; 30: 978-981 REVIEW ARTICLE J Med Genet: first published as 10.1136/jmg.30.12.978 on 1 December 1993. Downloaded from Dynamic mutations on the move Grant R Sutherland, Robert I Richards It is only a short time since the isolation and quences is rapidly increasing (table). These characterisation of the fragile X syndrome mu- include another fragile site (FRAXE) that may tation'-3 uncovered a new genetic element and be associated with mild mental retardation.'2 mechanism of mutation. The genetic element This fragile site has turned out to be similar in was an unstable DNA sequence resulting from structure to the fragile X (FRAXA), involving amplification of a naturally occurring poly- the same trinucleotide p(CCG)n and being morphic trinucleotide repeat, p(CCG)n. The close to a CpG island which is hypermethy- mechanism of mutation, which we have lated when the copy number exceeds approx- termed dynamic mutation,4 is the change (in- imately 200.* crease or decrease) in copy number of the The dynamic mutations characterised to trinucleotide repeat with the rate of change date fall into two categories probably deter- related to the number of copies present at any mined by whether the trinucleotide repeat is in time. This process, in which an initial change a translated or untranslated region of a gene. to a DNA sequence alters the chance of further The mutations in known or presumed changes to it, contrasts with classical or static untranslated regions, FRAXA, FRAXE, and mutation in which the product of a mutation is DM, appear to have little constraint on the no more likely to undergo further changes than number of repeats, which can range up to was the initial DNA sequence. -
General Contribution
24 Abstracts of 37th Annual Meeting A1 A SCREENING METHOD FOR FRAGILE X MUTATION: DETECTION OF THE CGG REPEAT IN FMR-1 GENE BY PCR WITH BIOTIN-LABELED PRIMER. ..Eiji NANBA, Kousaku OHNO and Kenzo TAKESHITA Division of Child Neurology, Institute of Neurological Sciences, Tot- tori University School of Medicine. Yonago We have developed a new polymerase chain reaction(PCR)-based method for detection of the CGG repeat in FMR-1 gene. No specific product from PCR was detected on the gel with ethidium bromide staining, because 7-deaza-2'-dGTP is necessary for amplification of this repeat. Biotin-labeled primer was used for PCR and the product was transferred to a nylon membrane followed the detection of biotin by Smilight kit. The size of PCR product from normal control were slightly various and around 300bp. No PCR product was detected from 3 fragile X male patients in 2 families diagnosed by cytogenetic examination. This method is useful for genetic screen- ing of male mental retardation patients to exclude the fragile X mutation. A2 DNA ANALYSISFOR FRAGILE X SYNDROME Osamu KOSUDA,Utak00GASA, ~.ideynki INH, a~ji K/NAGIJCltI, and Kazumasa ]tIKIJI (SILL Inc., Tokyo) Fragile X syndrome is X-linked disease having the amplification of (CG6)n repeat sequence in the chromsomeXq27.3. We performed Southern blot analysis using three probes recognized repetitive sequence resion. Normal controle showed 5.2Kb with Eco RI digest and 2.7Kb with Eco RI/Bss ttII digest as the germ tines by the Southern blot analysis. However, three cell lines established fro~ unrelated the patients with fragile X showed the abnormal bands between 5.2 and 7.7Kb with Eco RI digest, and between 2.7 and 7.7Kb with Eco aI/Bss HII digest. -
Transposon Variants and Their Effects on Gene Expression in Arabidopsis
Transposon Variants and Their Effects on Gene Expression in Arabidopsis Xi Wang, Detlef Weigel*, Lisa M. Smith* Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tu¨bingen, Germany Abstract Transposable elements (TEs) make up the majority of many plant genomes. Their transcription and transposition is controlled through siRNAs and epigenetic marks including DNA methylation. To dissect the interplay of siRNA–mediated regulation and TE evolution, and to examine how TE differences affect nearby gene expression, we investigated genome- wide differences in TEs, siRNAs, and gene expression among three Arabidopsis thaliana accessions. Both TE sequence polymorphisms and presence of linked TEs are positively correlated with intraspecific variation in gene expression. The expression of genes within 2 kb of conserved TEs is more stable than that of genes next to variant TEs harboring sequence polymorphisms. Polymorphism levels of TEs and closely linked adjacent genes are positively correlated as well. We also investigated the distribution of 24-nt-long siRNAs, which mediate TE repression. TEs targeted by uniquely mapping siRNAs are on average farther from coding genes, apparently because they more strongly suppress expression of adjacent genes. Furthermore, siRNAs, and especially uniquely mapping siRNAs, are enriched in TE regions missing in other accessions. Thus, targeting by uniquely mapping siRNAs appears to promote sequence deletions in TEs. Overall, our work indicates that siRNA–targeting of TEs may influence removal of sequences from the genome and hence evolution of gene expression in plants. Citation: Wang X, Weigel D, Smith LM (2013) Transposon Variants and Their Effects on Gene Expression in Arabidopsis. PLoS Genet 9(2): e1003255. -
Essential Trace Elements in Human Health: a Physician's View
Margarita G. Skalnaya, Anatoly V. Skalny ESSENTIAL TRACE ELEMENTS IN HUMAN HEALTH: A PHYSICIAN'S VIEW Reviewers: Philippe Collery, M.D., Ph.D. Ivan V. Radysh, M.D., Ph.D., D.Sc. Tomsk Publishing House of Tomsk State University 2018 2 Essential trace elements in human health UDK 612:577.1 LBC 52.57 S66 Skalnaya Margarita G., Skalny Anatoly V. S66 Essential trace elements in human health: a physician's view. – Tomsk : Publishing House of Tomsk State University, 2018. – 224 p. ISBN 978-5-94621-683-8 Disturbances in trace element homeostasis may result in the development of pathologic states and diseases. The most characteristic patterns of a modern human being are deficiency of essential and excess of toxic trace elements. Such a deficiency frequently occurs due to insufficient trace element content in diets or increased requirements of an organism. All these changes of trace element homeostasis form an individual trace element portrait of a person. Consequently, impaired balance of every trace element should be analyzed in the view of other patterns of trace element portrait. Only personalized approach to diagnosis can meet these requirements and result in successful treatment. Effective management and timely diagnosis of trace element deficiency and toxicity may occur only in the case of adequate assessment of trace element status of every individual based on recent data on trace element metabolism. Therefore, the most recent basic data on participation of essential trace elements in physiological processes, metabolism, routes and volumes of entering to the body, relation to various diseases, medical applications with a special focus on iron (Fe), copper (Cu), manganese (Mn), zinc (Zn), selenium (Se), iodine (I), cobalt (Co), chromium, and molybdenum (Mo) are reviewed. -
Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters
pharmaceuticals Review Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters Teresa Iannaccone 1, Carmine Sellitto 1,2,* , Valentina Manzo 1,2 , Francesca Colucci 1, Valentina Giudice 1 , Berenice Stefanelli 1 , Antonio Iuliano 1, Giulio Corrivetti 3 and Amelia Filippelli 1,2 1 Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; [email protected] (T.I.); [email protected] (V.M.); [email protected] (F.C.); [email protected] (V.G.); [email protected] (B.S.); [email protected] (A.I.); afi[email protected] (A.F.) 2 Clinical Pharmacology and Pharmacogenetics Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy 3 European Biomedical Research Institute of Salerno (EBRIS), 84125 Salerno, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-089673848 Abstract: Pharmacogenomics can identify polymorphisms in genes involved in drug pharma- cokinetics and pharmacodynamics determining differences in efficacy and safety and causing inter-individual variability in drug response. Therefore, pharmacogenomics can help clinicians in optimizing therapy based on patient’s genotype, also in psychiatric and neurological settings. Citation: Iannaccone, T.; Sellitto, C.; However, pharmacogenetic screenings for psychotropic drugs are not routinely employed in diagno- Manzo, V.; Colucci, F.; Giudice, V.; Stefanelli, B.; Iuliano, A.; Corrivetti, sis and monitoring of patients treated with mood stabilizers, such as carbamazepine and valproate, G.; Filippelli, A. Pharmacogenetics of because their benefit in clinical practice is still controversial. In this review, we summarize the current Carbamazepine and Valproate: Focus knowledge on pharmacogenetic biomarkers of these anticonvulsant drugs. -
Test ID: NGMEM
NEW TEST NOTIFICATION DATE: April 25, 2017 EFFECTIVE DATE: May 15, 2017 RED BLOOD CELL MEMBRANE SEQUENCING, VARIES Test ID: NGMEM USEFUL FOR: Providing a comprehensive genetic evaluation for patients with a personal or family history suggestive of an RBC membrane disorder Second-tier testing for patients in whom previous targeted gene mutation analyses were negative for a specific RBC membrane disorder Establishing a diagnosis of a hereditary RBC membrane disorder, allowing for appropriate management and surveillance of disease features based on the gene involved Identifying mutations within genes associated with phenotypic severity, allowing for predictive testing and further genetic counseling METHOD: Hereditary Mutation Detection by Next-Generation Sequencing (NGS) REFERENCE VALUES: An interpretive report will be provided. This next-generation sequencing assay is performed to test for the presence of a mutation in targeted regions of the following 15 genes and intronic regions: ANK1, EPB41, EPB42, GYPC, HBB, HBD, PIEZO1, RHAG, SLC2A1, SLC4A1, SPTA1, SPTB, STOM, UGT1A1, and XK. SPECIMEN REQUIREMENTS: Submit only 1 of the following specimens: Specimen Type: Peripheral blood (preferred) Container/Tube: Preferred: Lavender top (EDTA) or yellow top (ACD) Acceptable: Green top (heparin) Specimen Volume: 3 mL Specimen Stability: Ambient < or =14 days Collection Instructions: 1. Invert several times to mix blood. 2. Send specimen in original tube. 3. Label specimen as blood. Specimen Type: Extracted DNA Container/Tube: 1.5- to 2-mL tube with indication of volume and concentration of the DNA. Specimen Volume: Entire specimen Specimen Stability: Frozen/Refrigerated/Ambient < or =30 days Collection Instructions: Label specimen as extracted DNA and source of specimen. -
Genome Mapping Resolves Structural Variation Within Segmental Duplications Associated
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.30.071449; this version posted May 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. 1 Genome mapping resolves structural variation within segmental duplications associated 2 with microdeletion/microduplication syndromes 3 4 Authors 5 Yulia Mostovoy1,*, Feyza Yilmaz2,3,*, Stephen K. Chow1, Catherine Chu1, Chin Lin1, Elizabeth A. 6 Geiger3, Naomi J. L. Meeks3, Kathryn. C. Chatfield3,4, Curtis R. Coughlin II3, Pui-Yan Kwok1,5,6,#, 7 Tamim H. Shaikh3,# 8 9 Affiliations 10 1Cardiovascular Research Institute, UCSF School of Medicine, San Francisco, California 94143, 11 USA 12 2Department of Integrative Biology, University of Colorado Denver, Denver, Colorado 80204, 13 USA 14 3Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado 15 School of Medicine, Aurora, Colorado 80045, USA 16 4Department of Pediatrics, Section of Cardiology, University of Colorado School of Medicine, 17 Aurora, Colorado 80045, USA 18 5Department of Dermatology, and 6Institute for Human Genetics, UCSF School of Medicine, San 19 Francisco, California 94143, USA 20 21 * These two authors contributed equally to the work presented 22 # Address correspondence to: [email protected]; [email protected] 23 24 Running Title 25 Resolving structures within segmental duplications 26 27 Keywords 28 Segmental duplications, genome mapping, structural variation, genomic disorders 29 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.30.071449; this version posted May 2, 2020. -
Integrative Networks in Intellectual Disabilities
Conference 1st International Integrative Networks in Intellectual Disabilities 14-17 April, 2013 Coral Beach Hotel Paphos Cyprus Gene Networks Conference book 1st INTERNATIONAL GENCODYS CONFERENCE “Integrative Networks in Intellectual Disabilities” 14‐17 April, 2013 Coral Beach Hotel, Paphos, Cyprus MAIN SPONSOR AND ORGANISERS: EU project: GENCODYS Genetic and Epigenetic Networks in Cognitive Dysfunction EU 7th Framework Program Grant agreement no.: 241995 www.Gencodys.EU CO SPONSORS: WELCOME WELCOME We bid you a very warm welcome at the first International GENCODYS Conference. We hope that you will enjoy the scientific contents of this conference as well as its lovely settings, provided by the beautiful island of Cyprus and the hospitality of its people! The increasing power of sequencing allows the elucidation of causative genetic defects and risk factors in cognitive disorders (CD) by analysis of entire exomes and even complete genomes. A wide variety of chromosomal aberrations and a bewildering number of single gene mutations underlie intellectual disability (ID), and in a growing number of examples share a common etiology with other cognitive defects such as autism and schizophrenia. Elucidation of the complete landscape of all CD‐associated genes will allow us to recognize the underlying common pathological mechanisms. Already now, extensive functional interactions are seen between ID‐associated proteins and intricate networks are becoming apparent. Examples include protein networks driving synaptic morphology and plasticity and the epigenetic orchestration of neuronal gene expression. The European funded research consortium GENCODYS exploits a multilevel approach to resolve the integrative networks in intellectual disabilities. We are bringing together top researchers with complementary expertise and patient representatives to apply a systems biology approach to reveal the common molecular and cellular mechanisms leading to cognitive impairment and translational research possibilities. -
Gene Mutation and DNA Polymorphism Outline of This Chapter
Gene mutation and DNA polymorphism Outline of this chapter Gene Mutation DNA Polymorphism GeneGene MutationMutation Definition Major Types DefinitionDefinition A gene mutation is a change in the nucleotide sequence that composes a gene. Somatic mutations Germline mutations SomaticSomatic mutationsmutations are mutations that occur in cells of the body excluding the germline. Affects subsequent somatic cell descendants Limited to impact on the individual and not transmitted to offspring Germline mutations are mutations that occur in the germline cells Possibility of transmission to offspring Major Types Point mutations Insertion or deletion Fusion gene Dynamic mutation Point mutation substitution of one base with another Point mutation Transition purine replaces purine A G or pyrimidine replaces pyrimidine C T Transversion purine replaces pyrimidine A G or pyrimidine replaces purine C T What are the consequences? Within coding region: Silent mutation (same sense mutation) Missense mutation Nonsense mutation Stop codon mutation Within noncoding region: Splicing mutation Regulatory sequence mutation SilentSilent MutationMutation changes one codon for an amino acid to another codon for that amino acid no change in amino acid MissenseMissense mutationmutation A point mutation that exchanges one codon for another causing substitution of an amino acid Missense mutations may affect protein function severely, mildly or not at all. CGT AGT Hemoglobin Four globular proteins surrounding heme group with iron atom: two beta chains and two alpha chains Function is to carry oxygen in red blood cells from lungs to body and carbon dioxide from cells to lungs SingleSingle basebase changechange inin hemoglobinhemoglobin genegene causescauses sicklesickle cellcell anemiaanemia Wild-type mutant allele allele Wild-type mutant phenotype phenotype NonsenseNonsense mutationmutation A point mutation changing a codon for an amino acid into a stop codon (UAA, UAG or UGA).