Gene Mutation and DNA Polymorphism Outline of This Chapter
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ENZYME POLYMORPHISM and ADAPTATION ( Enzyme Polymorphism, Electrophor Esis, Neutral Hypothesis)
STADLER SYMP. Vo l . 7 ( 1 975) University of Missouri, Columbia - 91 ENZYME POLYMORPHISM AND ADAPTATION ( enzyme polymorphism, electrophor esis, neutral hypothesis) GEORGE B. JOHNSON Depa rtment of Biology Washin gt on University St. Louis, Missouri 631 30 SUMMARY After a brief resume of the controversy concerning the adaptive value of enzyme polymorphisms , a physiological hypo thesis is advanced that heterosis for enzymes of intermediary metabolism results from the differential kinetic behavior of the alleles, which in heterozygotes serve to buffer rate - deter mining reactions from environmental perturbations . Polymor phism within a population of alpine butterflies is examined in some detail , and the results strongly implicate ongoing selec tive processes. A more detailed understanding would seem to require more pointed in vivo physiological analyses of the polymorphic variants. A characterization of the physical na ture of the electrophoretic variants suggests that many vari ants do not involve a charge difference , while almost all in volve a significant conformational difference. The value of explicit error estimates associated with each data characteri zation is stressed throughout. INTRODUCTION With the extensive use in the last ten years of zone elec trophoresis as a genetic survey technique, it has become clear that level s of genet ic variability are quite h i gh in natural populations. The average levels of heterozygosity exceed 10% , 30% of examined loci are polymorphic . Thi s degree of varia bility is much higher than had been expected, and its inter pretation has become one of the central questions of popula tion genetics. Kimura and others have advanced the idea that this level of genetic variation reflects random events , the polymorphic enzyme alleles detected by electrophoresis actually having 92 JOHNSON little or no differential effect on fitness. -
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. -
Polymorphism Under Apostatic
Heredity (1984), 53(3), 677—686 1984. The Genetical Society of Great Britain POLYMORPHISMUNDER APOSTATIC AND APOSEMATIC SELECTION VINTON THOMPSON Department of Biology, Roosevelt University, 430 South Michigan Avenue, Chicago, Illinois 60805 USA Received31 .i.84 SUMMARY Selection for warning colouration in well-defended species should lead to a single colour form in each local population, but some species are locally polymor- phic for aposematic colour forms. Single-locus two-allele models of frequency- dependent selection indicate that combined apostatic and aposematic selection may maintain stable polymorphism for one, two or three aposematic forms, provided that at least one form is subject to net apostatic selection. Frequency- independent selective differences between colour forms broaden the possibilities for aposematic polymorphism but lead to monomorphism if too large. Concurrent apostatic and aposematic selection may explain polymorphism for warning colouration in a number of jumping or moderately unpalatable insects. 1. INTRODUCTION Polymorphism for warning colouration poses a paradox for evolutionists because, as Fisher (1958) seems to have been the first to note, selection for warning colouration (aposematic selection) should lead to monomorphism. Under aposematic selection predators tend to avoid previously encountered phenotypes of undesirable prey, so that the fitness of each phenotype increases as it becomes more common. Given the presence of two forms, each will suffer at the hands of predators conditioned to avoid the other and one will eventually prevail because as soon as it gets the upper hand numerically it will drive the other to extinction. Nonetheless, many species are polymorphic for colour forms that appear to be aposematic. The ladybird beetles (Coccinellidae) furnish a number of particularly striking examples (Hodek, 1973; and see illustration in Ayala, 1978). -
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. -
I Xio- and Made the Rather Curious Assumption That the Mutant Is
NOTES AND COMMENTS NATURAL SELECTION AND THE EVOLUTION OF DOMINANCE P. M. SHEPPARD Deportment of Genetics, University of Liverpool and E.B. FORD Genetic Laboratories, Department of Zoology, Oxford 1. INTRODUCTION CROSBY(i 963) criticises the hypothesis that dominance (or recessiveness) has evolved and is not an attribute of the allelomorph when it arose for the first time by mutation. None of his criticisms is new and all have been discussed many times. However, because of a number of apparent mis- understandings both in previous discussions and in Crosby's paper, and the fact that he does not refer to some important arguments opposed to his own view, it seems necessary to reiterate some of the previous discussion. Crosby's criticisms fall into two parts. Firstly, he maintains, as did Wright (1929a, b) and Haldane (1930), that the selective advantage of genes modifying dominance, being of the same order of magnitude as the mutation rate, is too small to have any evolutionary effect. Secondly, he criticises, as did Wright (5934), the basic assumption that a new mutation when it first arises produces a phenotype somewhat intermediate between those of the two homozygotes. 2.THE SELECTION COEFFICIENT INVOLVED IN THE EVOLUTION OF DOMINANCE Thereis no doubt that the selective advantage of modifiers of dominance is of the order of magnitude of the mutation rate of the gene being modified. Crosby (p. 38) considered a hypothetical example with a mutation rate of i xio-and made the rather curious assumption that the mutant is dominant in the absence of modifiers of dominance. -
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. -
Idiopathic Infertility As a Feature of Genome Instability
life Review Idiopathic Infertility as a Feature of Genome Instability Agrita Puzuka 1,2, Baiba Alksere 1,3, Linda Gailite 1 and Juris Erenpreiss 1,3,* 1 Scientific Laboratory of Molecular Genetics, Riga Stradins University, LV-1007 Riga, Latvia; [email protected] (A.P.); [email protected] (B.A.); [email protected] (L.G.) 2 Department of Biology and Microbiology, Riga Stradins University, LV-1007 Riga, Latvia 3 EAA Andrology Centre, Clinic IVF-Riga, LV-1010 Riga, Latvia * Correspondence: [email protected] Abstract: Genome instability may play a role in severe cases of male infertility, with disrupted sper- matogenesis being just one manifestation of decreased general health and increased morbidity. Here, we review the data on the association of male infertility with genetic, epigenetic, and environmental alterations, the causes and consequences, and the methods for assessment of genome instability. Male infertility research has provided evidence that spermatogenic defects are often not limited to testicular dysfunction. An increased incidence of urogenital disorders and several types of cancer, as well as overall reduced health (manifested by decreased life expectancy and increased morbidity) have been reported in infertile men. The pathophysiological link between decreased life expectancy and male infertility supports the notion of male infertility being a systemic rather than an isolated condition. It is driven by the accumulation of DNA strand breaks and premature cellular senescence. We have presented extensive data supporting the notion that genome instability can lead to severe male infertility termed “idiopathic oligo-astheno-teratozoospermia.” We have detailed that genome instability in men with oligo-astheno-teratozoospermia (OAT) might depend on several genetic Citation: Puzuka, A.; Alksere, B.; and epigenetic factors such as chromosomal heterogeneity, aneuploidy, micronucleation, dynamic Gailite, L.; Erenpreiss, J. -
By Duplicons Among Patients with Developmental Delay And/Or Congenital Malformations; Detection of Reciprocal and Partial Williams-Beuren Duplications
The human genome; you gain some, you lose some Kriek, M. Citation Kriek, M. (2007, December 6). The human genome; you gain some, you lose some. Retrieved from https://hdl.handle.net/1887/12479 Version: Corrected Publisher’s Version Licence agreement concerning inclusion of doctoral License: thesis in the Institutional Repository of the University of Leiden Downloaded from: https://hdl.handle.net/1887/12479 Note: To cite this publication please use the final published version (if applicable). Chapter II-2 Copy number variation in regions flanked (or unflanked) by duplicons among patients with developmental delay and/or congenital malformations; detection of reciprocal and partial Williams-Beuren duplications Marjolein Kriek1, Stefan J White1, Karoly Szuhai2, Jeroen Knijnenburg2, Gert-Jan B van Ommen1, Johan T den Dunnen1 and Martijn H Breuning1 1Center for Human and Clinical Genetics, Leiden University Medical Center, The Netherlands; 2Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands Eur J Hum Genet. 2006 Feb;14(2):180-9 63 Chapter 2 Summary Duplicons, that is, DNA sequences with minimum length 10 kb and a high sequence similarity, are known to cause unequal homologous recombination, leading to deletions and the reciprocal duplications. In this study, we designed a Multiplex Amplifiable Probe Hybridisation (MAPH) assay containing 63 exon-specific single-copy sequences from within a selection of the 169 regions flanked by duplicons that were identified, at a first pass, in 2001. Subsequently, we determined the frequency of chromosomal rear- rangements among patients with developmental delay (DD) and/or congenital mal- formations (CM). In addition, we tried to identify new regions involved in DD/CM using the same assay. -
Population Genetics of Polymorphism and Divergence Stanley A
Population Genetics of Polymorphism and Divergence Stanley A. Sawyer∗, † and Daniel L. Hartl† ∗Department of Mathematics, Washington University, St. Louis, Missouri 63130, †Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110 November 3, 1992 ABSTRACT Frequencies of mutant sites are modeled as a Poisson random field in two species that share a sufficiently recent common ancestor. The selective effect of the new alleles can be favorable, neutral, or detrimental. The model is applied to the sample configurations of nucleotides in the alcohol dehydrogenase gene (Adh) in Drosophila simulans and D. yakuba (McDonald and Kreitman 1991, Nature 351: 652–654). Assuming a synonymous mutation rate of 1.5 × 10−8 per site per year and 10 generations per year, we obtain 6 estimates for the effective population size (Ne =6.5 × 10 ), the species divergence time −6 (tdiv =3.74 Myr), and an average selection coefficient (σ =1.53 × 10 per generation for advantageous or mildly detrimental replacements), although it is conceivable that only two of the amino acid replacements were selected and the rest neutral. The analysis, which includes a sampling theory for the independent infinite sites model with selection, also suggests the estimate that the number of amino acids in the enzyme that are susceptible to favorable mutation is in the range 2–23 out of 257 total possible codon positions at any one time. The approach provides a theoretical basis for the use of a 2 × 2 contingency table to compare fixed differences and polymorphic sites with silent sites and amino acid replacements. t has been more than 25 years since Lewontin have been more at odds, and a great controversy en- I and Hubby (1966) first demonstrated high levels sued.