Types of Mutations: Spontaneous Mutations Dr
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Structural Effects of Point Mutations in Proteins Suvethigaa Shanthirabalan, Jacques Chomilier, Mathilde Carpentier
Structural effects of point mutations in proteins Suvethigaa Shanthirabalan, Jacques Chomilier, Mathilde Carpentier To cite this version: Suvethigaa Shanthirabalan, Jacques Chomilier, Mathilde Carpentier. Structural effects of point muta- tions in proteins. Proteins - Structure, Function and Bioinformatics, Wiley, 2018, 86 (8), pp.853-867. 10.1002/prot.25499. hal-01909365 HAL Id: hal-01909365 https://hal.sorbonne-universite.fr/hal-01909365 Submitted on 31 Oct 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Structural effects of point mutations in proteins Suvethigaa Shanthirabalan1, Jacques Chomilier2, Mathilde Carpentier1,2 1. Institut Systématique Evolution Biodiversité (ISYEB), Sorbonne Université, MNHN, CNRS, EPHE, Paris, France. 2. Sorbonne Université, CNRS, MNHN, IRD, IMPMC, BiBiP, Paris, France Corresponding author: [email protected] Mail: [email protected]; [email protected]; [email protected] Abstract A structural database of eleven families of chains differing by a single amino acid substitution has been built. Another structural dataset of 5 families with identical sequences has been used for comparison. The RMSD computed after a global superimposition of the mutated protein on each native one is smaller than the RMSD calculated among proteins of identical sequences. -
The Mutability and Repair of DNA
B.Sc (Hons) Microbiology (CBCS Structure) C-7: Molecular Biology Unit 2: Replication of DNA The Mutability and Repair of DNA Dr. Rakesh Kumar Gupta Department of Microbiology Ram Lal Anand College New Delhi - 110021 Reference – Molecular Biology of the Gene (6th Edition) by Watson et. al. Pearson education, Inc Principles of Genetics (8th Edition) by D. Peter Snustad, D. Snustad, Eldon Gardner, and Michael J. Simmons, Wiley publications Replication errors and their repair The Nature of Mutations: • Transitions: A kind of the simplest mutation which is pyrimidine-to-pyrimidine and purine-to- purine substitutions such as T to C and A to G • Transversions: The other kind of mutation which are pyrimidine-to-purine and purine-to- pyrimidine substitutions such as T to A or G and ATransitions to C or T. Transversions 8 types 4 types Synonymous substitution Non synonymous substitution • Point mutations: Mutations that alter a single nucleotide Other kinds of mutations (which cause more drastic changes in DNA): • Insertions • Deletions • Gross rearrangements of Thesechromosome mutations might be caused by insertion by transposon or by aberrant action of cellular recombination processes. Mutation • Substitution, deletion, or insertion of a base pair. • Chromosomal deletion, insertion, or rearrangement. Somatic mutations occur in somatic cells and only affect the individual in which the mutation arises. Germ-line mutations alter gametes and passed to the next generation. Mutations are quantified in two ways: 1. Mutation rate = probability of a particular type of mutation per unit time (or generation). 2. Mutation frequency = number of times a particular mutation occurs in a population of cells or individuals. -
Genetic Causes.Pdf
1 September 2015 Genetic causes of childhood apraxia of speech: Case‐based introduction to DNA, inheritance, and clinical management Beate Peter, Ph.D., CCC‐SLP Assistant Professor Dpt. of Speech & Hearing Science Arizona State University Adjunct Assistant Professor AG Dpt. of Communication Sciences & Disorders ATAGCT Saint Louis University T TAGCT Affiliate Assistant Professor Dpt. of Speech & Hearing Sciences University of Washington 1 Disclosure Statement Disclosure Statement Dr. Peter is co‐editor of a textbook on speech development and disorders (B. Peter & A. MacLeod, Eds., 2013), for which she may receive royalty payments. If she shares information about her ongoing research study, this may result in referrals of potential research participants. She has no financial interest or related personal interest of bias in any organization whose products or services are described, reviewed, evaluated or compared in the presentation. 2 Agenda Topic Concepts Why we should care about genetics. Case 1: A sporadic case of CAS who is missing a • Cell, nucleus, chromosomes, genes gene. Introduction to the language of genetics • From genes to proteins • CAS can result when a piece of DNA is deleted or duplicated Case 2: A multigenerational family with CAS • How the FOXP2 gene was discovered and why research in genetics of speech and language disorders is challenging • Pathways from genes to proteins to brain/muscle to speech disorder Case 3: One family's quest for answers • Interprofessional teams, genetic counselors, medical geneticists, research institutes • Early signs of CAS, parent education, early intervention • What about genetic testing? Q&A 3 “Genetic Causes of CAS: Case-Based Introduction to DNA, Inheritance and Clinical Management,” Presented by: Beate Peter, PhD, CCC-SLP, September 29, 2015, Sponsored by: CASANA 2 Why should you care about genetics? 4 If you are a parent of a child with childhood apraxia of speech … 5 When she was in preschool, He doesn’t have any friends. -
Mutation by Dr. Ty C.M. Hoffman
Mutation by Dr. Ty C.M. Hoffman Slide 1 Transcription features a one-to-one correspondence between DNA nucleotides in the gene and RNA nucleotides in the RNA transcript. However, the four nucleotide types used in RNA are insufficient to individually specify all twenty biological amino acids during translation. Instead, a sequence of three mRNA nucleotides (collectively called a codon) specifies a single amino acid. Since there are three nucleotide positions within a codon, and each position can be occupied by any of four types of nucleotide, there are sixty-four possible codons. This is more than enough to specify the twenty biological amino acids. Slide 2 The genetic code is universal in that all organisms (with very few exceptions) use the same code for specifying amino acids with mRNA codons. The genetic code is redundant in that more than one codon can specify the same amino acid. This is because there are more types of codons than there are types of amino acids used by organisms. The genetic code is not ambiguous, however, because each codon always specifies the same amino acid. Four of the codons serve special functions. One operates as a start codon (signaling initiation of translation), and three codons operate as stop codons (signaling the termination of translation). Slide 3 Mutation is a random change in the DNA sequence of nucleotides. Mutation can be purely accidental (by a mistake made during DNA replication), or mutation can result from exposure of DNA to a mutagen (something that causes mutation). Mutations can be classified into two major types: • Base-pair substitutions do not change the number of nucleotides in the DNA, because one base pair is substituted for another. -
Bio 102 Practice Problems Genetic Code and Mutation
Bio 102 Practice Problems Genetic Code and Mutation Multiple choice: Unless otherwise directed, circle the one best answer: 1. Choose the one best answer: Beadle and Tatum mutagenized Neurospora to find strains that required arginine to live. Based on the classification of their mutants, they concluded that: A. one gene corresponds to one protein. B. DNA is the genetic material. C. "inborn errors of metabolism" were responsible for many diseases. D. DNA replication is semi-conservative. E. protein cannot be the genetic material. 2. Choose the one best answer. Which one of the following is NOT part of the definition of a gene? A. A physical unit of heredity B. Encodes a protein C. Segement of a chromosome D. Responsible for an inherited characteristic E. May be linked to other genes 3. A mutation converts an AGA codon to a TGA codon (in DNA). This mutation is a: A. Termination mutation B. Missense mutation C. Frameshift mutation D. Nonsense mutation E. Non-coding mutation 4. Beadle and Tatum performed a series of complex experiments that led to the idea that one gene encodes one enzyme. Which one of the following statements does not describe their experiments? A. They deduced the metabolic pathway for the synthesis of an amino acid. B. Many different auxotrophic mutants of Neurospora were isolated. C. Cells unable to make arginine cannot survive on minimal media. D. Some mutant cells could survive on minimal media if they were provided with citrulline or ornithine. E. Homogentisic acid accumulates and is excreted in the urine of diseased individuals. 5. -
Large Accumulation of Mrna and DNA Point Modi¢Cations in a Plant
FEBS Letters 472 (2000) 14^16 FEBS 23560 View metadata, citation and similar papers at core.ac.uk brought to you by CORE Large accumulation of mRNA and DNA point modi¢cationsprovided in by a Elsevier plant - Publisher Connector senescent tissue Maria Plaa;*, Anna Jofre¨a, Maria Martellb, Marisa Molinasa, Jordi Go¨mezb aLaboratori del Suro, Universitat de Girona, Campus Montilivi sn, E-17071 Girona, Spain bLiver Unit, Department of Medicine, Universitat Auto©noma de Barcelona, Hospital General Universitari Vall d'Hebron, E-08035 Barcelona, Spain Received 26 January 2000 Edited by Takashi Gojobori We investigated the frequency of cDNA modi¢cation in Abstract Although nucleic acids are the paradigm of genetic information conservation, they are inherently unstable molecules cork (phellem) compared to a normally growing young tissue that suffer intrinsic and environmental damage. Oxidative stress (root tip) using cork-oak (Quercus suber) as a model system. has been related to senescence and aging and, recently, it has For this purpose, we analyzed a population of Qs_hsp17 been shown that mutations accumulate at high frequency in mRNA sequences (reverse transcription PCR products form mitochondrial DNA with age. We investigated RNA and DNA position 32^401, AC AJ000691) in cork and in root tip tissue modifications in cork, a senescent plant tissue under high [6]. Cork (phellem) is an external layer of protective tissue, endogenous oxidative stress conditions. When compared to consisting of several layers of cells that deposit large amounts normally growing young tissue, cork revealed an unexpected of suberin and undergo programmed cell death. Due to phen- high frequency of point modifications in both cDNA (Pn = oxy radicals generated during suberin synthesis [7,8], cork 1/1784) and nuclear DNA (Pn = 1/1520). -
Point Mutations Underlying NF1 and NF2 and Increased Risk of Malignancy
Central Annals of Otolaryngology and Rhinology Mini Review *Corresponding author Andrea L.O. Hebb, MSc, PhD, RN, Maritime Lateral Skull Base Clinic, Otolaryngology, Neurosurgery and the Point Mutations Underlying NF1 Stereotactic Radiotherapy Group QEII Health Science Centre, Halifax, Canada; Email: [email protected] and NF2 and Increased Risk of Submitted: 12 February 2020 Accepted: 25 February 2020 Published: 27 February 2020 Malignancy ISSN: 2379-948X Copyright 1 2 3,4 3,4 Myles Davidson , Haupt TS , Morris DP , Shoman NM , © 2020 Davidson M, et al. 2,4 1,2,4 Walling SA , and Hebb ALO * OPEN ACCESS 1Department of Psychology, Saint Mary’s University, Canada 2Division of Neurosurgery, Dalhousie University, Canada Keywords 3 Division of Otolaryngology, Dalhousie University, Canada • Neurofibromatosis 4 Maritime Lateral Skull Base Clinic, Otolaryngology, Neurosurgery and the Stereotactic • Missense mutation Radiotherapy Group QEII Health Science Centre, Canada • Frameshift mutation • Nonsense mutation Abstract • KRAS gene • Colorectal cancer Neurofibromatosis Type-1 and Neurofibromatosis Type-2 are autosomal dominant • Acoustic neuroma tumor suppressor disorders that result from inherited or spontaneous mutations in • Vestibular schwannoma their respective genes. Neurofibromatosis Type-1 has been attributed to a non-sense • Meningioma mutation in chromosome 17 and Neurofibromatosis Type-2 a point mutation in its gene on chromosome 22. The following discussion briefly reviews point and frameshift mutations and explores the relationship between point mutations and development of malignancies in patients with Neurofibromatosis Type-1 and Neurofibromatosis Type-2. INTRODUCTION producing phenylalanine hydroxylase, the majority of which are missense mutations [4]. A point mutation is the change of one base for another in the DNA sequence. -
Clinical and Genetic Characteristics and Prenatal Diagnosis of Patients
Lin et al. Orphanet J Rare Dis (2020) 15:317 https://doi.org/10.1186/s13023-020-01599-y RESEARCH Open Access Clinical and genetic characteristics and prenatal diagnosis of patients presented GDD/ID with rare monogenic causes Liling Lin1, Ying Zhang1, Hong Pan1, Jingmin Wang2, Yu Qi1 and Yinan Ma1* Abstract Background: Global developmental delay/intellectual disability (GDD/ID), used to be named as mental retardation (MR), is one of the most common phenotypes in neurogenetic diseases. In this study, we described the diagnostic courses, clinical and genetic characteristics and prenatal diagnosis of a cohort with patients presented GDD/ID with monogenic causes, from the perspective of a tertiary genetic counseling and prenatal diagnostic center. Method: We retrospectively analyzed the diagnostic courses, clinical characteristics, and genetic spectrum of patients presented GDD/ID with rare monogenic causes. We also conducted a follow-up study on prenatal diagnosis in these families. Pathogenicity of variants was interpreted by molecular geneticists and clinicians according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Results: Among 81 patients with GDD/ID caused by rare monogenic variants it often took 0.5–4.5 years and 2–8 referrals to obtain genetic diagnoses. Devlopmental delay typically occurred before 3 years of age, and patients usu- ally presented severe to profound GDD/ID. The most common co-existing conditions were epilepsy (58%), micro- cephaly (21%) and facial anomalies (17%). In total, 111 pathogenic variants were found in 62 diferent genes among the 81 pedigrees, and 56 variants were novel. The most common inheritance patterns in this outbred Chinese popula- tion were autosomal dominant (AD; 47%), following autosomal recessive (AR; 37%), and X-linked (XL; 16%). -
Methods for Detection of Point Mutations: Performance and Quality
Clinical Chemistry 43:7 1114–1128 (1997) Review Methods for detection of point mutations: performance and quality assessment Downloaded from https://academic.oup.com/clinchem/article/43/7/1114/5640834 by guest on 29 September 2021 Peter Nollau and Christoph Wagener*, on behalf of the IFCC Scientific Division, Committee on Molecular Biology Techniques We give an overview of current methods for the detec- 10) What kind of quality assessment can be achieved? tion of point mutations as well as small insertions and Here, different methods for the detection of point muta- deletions in clinical diagnostics. For each method, the tions and small deletions or insertions will be discussed following characteristics are specified: (a) principle, (b) on the basis of the above criteria (for simplification, we major modifications, (c) maximum fragment size that shall refer to point mutations only in the text, though in can be analyzed, (d) ratio and type of mutations that can general, small deletions or insertions are detected equally be detected, (e) minimum ratio of mutant to wild-type well by the methods described). In general, PCR is either alleles at which mutations can be detected, and (f) used for the generation of DNA fragments, or is part of detection methods. Special attention is paid to the the detection method. Screening methods for unknown possibilities of quality assessment and the potential for mutations as well as methods for the detection of known standardization and automation. mutations are included. Though DNA sequencing tech- niques will not be covered, we stress that DNA sequenc- INDEXING TERMS: alleles • electrophoresis • gene insertions ing is considered the gold standard and remains the • gene deletions • polymerase chain reaction definitive procedure for the detection of mutations so far. -
Computational Genomics and Genetics of Developmental Disorders
Computational genomics and genetics of developmental disorders Hongjian Qi Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2018 © 2018 Hongjian Qi All Rights Reserved ABSTRACT Computational genomics and genetics of developmental disorders Hongjian Qi Computational genomics is at the intersection of computational applied physics, math, statistics, computer science and biology. With the advances in sequencing technology, large amounts of comprehensive genomic data are generated every year. However, the nature of genomic data is messy, complex and unstructured; it becomes extremely challenging to explore, analyze and understand the data based on traditional methods. The needs to develop new quantitative methods to analyze large-scale genomics datasets are urgent. By collecting, processing and organizing clean genomics datasets and using these datasets to extract insights and relevant information, we are able to develop novel methods and strategies to address specific genetics questions using the tools of applied mathematics, statistics, and human genetics. This thesis describes genetic and bioinformatics studies focused on utilizing and developing state-of-the-art computational methods and strategies in order to identify and interpret de novo mutations that are likely causing developmental disorders. We performed whole exome sequencing as well as whole genome sequencing on congenital diaphragmatic hernia parents-child trios and identified a new candidate risk gene MYRF. Additionally, we found male and female patients carry a different burden of likely-gene-disrupting mutations, and isolated and complex patients carry different gene expression levels in early development of diaphragm tissues for likely-gene-disrupting mutations. -
Activation of the Ha-, Ki-, and N-Ras Genes in Chemically Induced Liver Tumors from CD-I Mice Sujata Mananu' Richard D
(CANCER RESEARCH 52. 3347-3352. June 15. 1992] Activation of the Ha-, Ki-, and N-ras Genes in Chemically Induced Liver Tumors from CD-I Mice Sujata Mananu' Richard D. Storer, Srinivasa Prahalada, Karen R. Leander, Andrew R. Kraynak, Brian J. Ledwith, Matthew J. van Zwieten, Matthews O. Bradley, and Warren W. Nichols Department of Safety Assessment, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486 ABSTRACT although the frequency of these mutations varies among mouse strains (6, 10-13). Previous studies in B6C3F,2 mice demon We compared the profilo of ras gene mutations in spontaneous CD-I strated that liver tumors induced by some genotoxic carcinogens mouse liver tumors with that found in liver tumors that were induced by a single i.p. injection of either 7,12-dimethylbenz(a)anthracene(DMBA), (6, 14, 15) and nongenotoxic carcinogens (11) had different 4-aminoazobenzene, Ar-hydroxy-2-acetylaminofluorene, or /V-nitrosodi- frequencies or profiles of ras gene point mutations than were ethylamine. By direct sequencing of polymerase chain reaction-amplified seen in spontaneous tumors. However, B6C3F, mouse liver tumor DNA, the carcinogen-induced tumors were found to have much tumors induced by benzidine (11), N-OH-AAF (14), and DEN higher frequencies of ras gene activation than spontaneous tumors. Fur (16) were reported to have a similar pattern of Ha-ras codon thermore, each carcinogen caused specific types of ras mutations not 61 mutations to that seen in spontaneous liver tumors. detected in spontaneous tumors, including several novel mutations not Determining the general applicability of ras gene analysis for previously associated with either the carcinogen or mouse hepatocarcin- distinguishing chemically induced tumors from spontaneous ogenesis. -
Teacher Materials (PDF)
The Making of the Fittest: LESSON The Birth and Death of Genes TEACHER MATERIALS THE MOLECULAR EVOLUTION OF GENE BIRTH AND DEATH OVERVIEW This advanced lesson describes how mutation is a key element in both the birth and death of genes. Students proceed through a series of presentation slides that include background information, examples, and embedded video, and animation links. Questions challenge students to synthesize information and apply what they learn regarding how genes are gained and lost through evolutionary time. KEY CONCEPTS AND LEARNING OBJECTIVES • Mutations are changes in an organism’s DNA. They occur at random. • Whether or not a mutation has an effect on an organism’s traits depends on the type of mutation and its location. • Mutations can result in both the appearance of new genes and the loss of existing genes. • One way that a new gene can arise is when a gene is duplicated and one copy (or both copies) of the gene accumulates mutations, which change the function of the gene. • One way that a gene can be lost is when one or more mutations accumulate that destroy its function. Students will be able to • analyze gene sequences and transcribe DNA into messenger RNA (mRNA); • translate mRNA into a sequence of amino acids by using a genetic code chart; and • compare wild-type and mutated DNA sequences to determine the type of mutation present. CURRICULUM CONNECTIONS Curriculum Standards NGSS (April 2013) HS-LS1-1, HS-LS3-1, HS-LS3-2, HS-LS4-2, HS-LS4-4, HS-LS4-5 HS.LS1.A, HS.LS3.A, HS.LS3.B, HS.LS4.B, HS.LS4.C Common Core