Bio 102 Practice Problems Genetic Code and Mutation
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Missense Mutations of MADH4: Characterization of the Mutational Hot Spot and Functional Consequences in Human Tumors
Vol. 10, 1597–1604, March 1, 2004 Clinical Cancer Research 1597 Featured Article Missense Mutations of MADH4: Characterization of the Mutational Hot Spot and Functional Consequences in Human Tumors Christine A. Iacobuzio-Donahue,1 Jason Song,5 Introduction Giovanni Parmiagiani,4 Charles J. Yeo,2,3 Human pancreatic ductal adenocarcinomas inactivate the Ralph H. Hruban,1,2 and Scott E. Kern2 tumor suppressor gene MADH4 (DPC4, SMAD4) with a high frequency (1). This inactivation occurs most commonly by Departments of 1Pathology, 2Oncology, 3Surgery, and 4Public Health, The Johns Hopkins Medical Institutions, Baltimore, Maryland, and homozygous deletion (HD), but some tumors may also inacti- 5Temple University School of Medicine, Philadelphia, Pennsylvania vate the gene by loss of heterozygosity (LOH) coupled with a mutation in the remaining allele. Inactivation by nonsense mu- tation may cause the loss of protein expression by enhanced Abstract proteosomal degradation (2, 3). Even when expressed as protein, Purpose and Experimental Design: The mutational spec- missense mutations may result in loss of a specific function of trum of MADH4 (DPC4/SMAD4) opens valuable insights the Madh4 protein such as DNA binding or Smad protein into the functions of this protein that confer its tumor- interactions (2–9). Thus, the location of these mutations can suppressive nature in human tumors. We present the provide clues to key structural features that mediate the tumor- MADH4 genetic status determined on a new set of pancre- suppressive function of MADH4. atic, biliary, and duodenal cancers with comparison to the Members of the Smad protein family, including Madh4, mutational data reported for various tumor types. -
Effects of Single Amino Acid Deficiency on Mrna Translation Are Markedly
www.nature.com/scientificreports OPEN Efects of single amino acid defciency on mRNA translation are markedly diferent for methionine Received: 12 December 2016 Accepted: 4 May 2018 versus leucine Published: xx xx xxxx Kevin M. Mazor, Leiming Dong, Yuanhui Mao, Robert V. Swanda, Shu-Bing Qian & Martha H. Stipanuk Although amino acids are known regulators of translation, the unique contributions of specifc amino acids are not well understood. We compared efects of culturing HEK293T cells in medium lacking either leucine, methionine, histidine, or arginine on eIF2 and 4EBP1 phosphorylation and measures of mRNA translation. Methionine starvation caused the most drastic decrease in translation as assessed by polysome formation, ribosome profling, and a measure of protein synthesis (puromycin-labeled polypeptides) but had no signifcant efect on eIF2 phosphorylation, 4EBP1 hyperphosphorylation or 4EBP1 binding to eIF4E. Leucine starvation suppressed polysome formation and was the only tested condition that caused a signifcant decrease in 4EBP1 phosphorylation or increase in 4EBP1 binding to eIF4E, but efects of leucine starvation were not replicated by overexpressing nonphosphorylatable 4EBP1. This suggests the binding of 4EBP1 to eIF4E may not by itself explain the suppression of mRNA translation under conditions of leucine starvation. Ribosome profling suggested that leucine deprivation may primarily inhibit ribosome loading, whereas methionine deprivation may primarily impair start site recognition. These data underscore our lack of a full -
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. -
Detecting Translational Regulation by Change Point Analysis of Ribosome Profiling Datasets
bioRxiv preprint doi: https://doi.org/10.1101/003210; this version posted March 5, 2014. 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 4.0 International license. Detecting translational regulation by change point analysis of ribosome profiling datasets Zupanic A1, Meplan C2, Grellscheid SN3, Mathers JC1, Kirkwood TBL1, Hesketh JE2, Shanley DP1 1Centre for Integrated Systems Biology of Ageing & Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle-upon-Tyne, NE4 5PL, UK 2Institute for Cell and Molecular Biosciences and Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK 3School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK Running title: Translational regulation in ribosome profiles Keywords: ribosome profiling, translation regulation, change point, mathematical model Corresponding author: Daryl Shanley Centre for Integrated Systems Biology of Ageing & Nutrition, Institute for Ageing and Health, Newcastle University, NE4 5PL, UK Email: [email protected] Fax: +441912481101 1 bioRxiv preprint doi: https://doi.org/10.1101/003210; this version posted March 5, 2014. 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 4.0 International license. Abstract Ribo-Seq maps the location of translating ribosomes on mature mRNA transcripts. While ribosome density is constant along the length of the mRNA coding region, it can be altered by translational regulatory events. -
YEAST CELLS MAY USE AUC OR AAG AS INITIATION CODON for PROTEIN SYNTHESIS by OLE OLSEN
Carlsberg Res. Commun. Vol. 52, p. 83-90, 1987 YEAST CELLS MAY USE AUC OR AAG AS INITIATION CODON FOR PROTEIN SYNTHESIS by OLE OLSEN Department of Physiology, Carlsberg Laboratory, Gamle Cadsbergvej 10, DK-2500 Copenhagen Valby Keywords: Recombinant DNA, translation initiation, secretion A yeast expression plasmid without an ATG codon for initiation of mouse a-amylase protein synthesis directs the synthesis and secretion of active enzyme indistinguishable from both native mouse a-amylase and amylase synthesized from plasmids with normal AT(3 initiation codons. The initiation of amylase synthesis directed by this plasmid is at either an AUC or an AAG codon. In either case the amino acid sequence of the hydrophobic core and peptidase cleaving region of the signal peptide are normal, and the protein translation remains in frame with the structural gene of the mouse a-amylase. 1. INTRODUCTION mal context for initiation was 6NNAUGGA A where Initiation of protein synthesis in eukaryotes is a purine in position -3 (three nucleotides up- catalysed by a relatively large number of specific stream of the AUG initiator codon) is most eukaryotic initation factors (eIFs) bringing highly conserved. about the formation of the 80S initiation com- Until recently it was generally believed that plex composed ofmRNA, an 80S ribosome and eukaryotic ribosomes initiate exclusively at met-tRNAi (l 3). Eukaryotic met-tRNAi differs AUG codons although it had been shown by from its prokaryotic counterpart by being asso- RAJBHANDARYand GHOSH (24) that yeast met- ciated with the 40S pre-initation complex before tRNAi may function with either AUG or GUG binding to mRNA (13). -
Coincident Two Mutations and One Single Nucleotide Polymorphism of the PTCH1 Gene in a Family with Naevoid Basal Cell Carcinoma Syndrome
Letters to the Editor 635 Coincident Two Mutations and One Single Nucleotide Polymorphism of the PTCH1 Gene in a Family with Naevoid Basal Cell Carcinoma Syndrome Shoko Abe1, Kenji Kabashima1*, Jun-ichi Sakabe1, Takatoshi Shimauchi1, Zhang Yan2, Tetsuji Okamoto2 and Yoshiki Tokura1 1Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, and 2Department of Molecular Oral Medicine and Maxillofacial Surgery 1, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. E-mail: [email protected] Accepted May 7, 2008. Sir, at nucleotide position 667 within exon 3 and an intervening se- Naevoid basal cell carcinoma syndrome (NBCCS, OMIM quence (IVS)16 -3T > C, and a SNP; IVS10 -8T > C, were detected in all three cases. A deletion of AGAC causes a frameshift and a #109400), also called Gorlin’s syndrome, is an autosomal subsequent stop codon in exon 3, which prematurely truncates dominant disease that affects about 1 in 60,000 indivi- the protein (Fig. 1a). In addition, the IVS16 -3T > C could lead duals (1, 2). NBCCS is associated with various skeletal to an aberrant splicing and truncation of PTCH1 (10–12). and neurocutaneous abnormalities. Major manifestations To detect the expression level of PTCH1 protein in the skin, are multiple basal cell carcinomas (BCCs), odontogenic an immunohistochemical study was performed using goat poly- clonal anti-PTCH1 antibody (G-19; Santa Cruz Biotechnology, keratocysts, palmoplantar dyskeratotic pits and intra- Santa Cruz, CA, USA). Enzyme reactions were developed with cranial calcification (3). In addition, rib and vertebral conventional substrates for diamino-benzidine (Sigma, St Louis, malformations, epidermal cysts, macrocephaly, facial MO, USA) (13). -
Antibiotic Resistance by High-Level Intrinsic Suppression of a Frameshift Mutation in an Essential Gene
Antibiotic resistance by high-level intrinsic suppression of a frameshift mutation in an essential gene Douglas L. Husebya, Gerrit Brandisa, Lisa Praski Alzrigata, and Diarmaid Hughesa,1 aDepartment of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala SE-751 23, Sweden Edited by Sankar Adhya, National Institutes of Health, National Cancer Institute, Bethesda, MD, and approved January 4, 2020 (received for review November 5, 2019) A fundamental feature of life is that ribosomes read the genetic (unlikely if the DNA sequence analysis was done properly), that the code in messenger RNA (mRNA) as triplets of nucleotides in a mutants carry frameshift suppressor mutations (15–17), or that the single reading frame. Mutations that shift the reading frame gen- mRNA contains sequence elements that promote a high level of ri- erally cause gene inactivation and in essential genes cause loss of bosomal shifting into the correct reading frame to support cell viability viability. Here we report and characterize a +1-nt frameshift mutation, (10). Interest in understanding these mutations goes beyond Mtb and centrally located in rpoB, an essential gene encoding the beta-subunit concerns more generally the potential for rescue of mutants that ac- of RNA polymerase. Mutant Escherichia coli carrying this mutation are quire a frameshift mutation in any essential gene. We addressed this viable and highly resistant to rifampicin. Genetic and proteomic exper- by isolating a mutant of Escherichia coli carrying a frameshift mutation iments reveal a very high rate (5%) of spontaneous frameshift suppres- in rpoB and experimentally dissecting its genotype and phenotypes. sion occurring on a heptanucleotide sequence downstream of the mutation. -
Truncating Mutations in Severe Intellectual Disability
European Journal of Human Genetics (2014) 22, 289–292 & 2014 Macmillan Publishers Limited All rights reserved 1018-4813/14 www.nature.com/ejhg SHORT REPORT Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability Frederic Tran Mau-Them1, Marjolaine Willems*,1, Beate Albrecht2, Elodie Sanchez1, Jacques Puechberty1, Sabine Endele3, Anouck Schneider4, Nathalie Ruiz Pallares4,5, Chantal Missirian6, Francois Rivier7, Manon Girard4, Muriel Holder8, Sylvie Manouvrier8, Isabelle Touitou5, Genevieve Lefort4, Pierre Sarda1, Anne Moncla7, Severine Drunat9, Dagmar Wieczorek2 and David Genevieve1 Intellectual disability (ID) is frequent in the general population, with 1 in 50 individuals directly affected worldwide. The multiple etiologies include X-linked ID (XLID). Among syndromic XLID, few syndromes present severe ID associated with postnatal microcephaly and midline stereotypic hand movements. We report on three male patients with ID, midline stereotypic hand movements, hypotonia, hyperkinesia, strabismus, as well as seizures (2/3), and non-inherited and postnatal onset microcephaly (2/3). Using array CGH and exome sequencing we characterised two truncating mutations in IQSEC2, namely two de novo intragenic duplication mapped to the Xp11.22 region and a nonsense mutation in exon 7. We propose that truncating mutations in IQSEC2 are responsible for syndromic severe ID in male patients and should be screened in patients without mutations in MECP2, FOXG1, CDKL5 and MEF2C. European Journal of Human Genetics (2014) 22, 289–292; doi:10.1038/ejhg.2013.113; published online 15 May 2013 Keywords: syndromic X-linked intellectual disability; microcephaly; IQSEC2-truncating mutations INTRODUCTION native to the south of France. Pregnancy was uneventful. The boy was born at Intellectual disability (ID) is defined by substantial limitations in 37 ½ weeks of gestation full term by caesarean section due to an abnormal cognitive functioning (intellectual quotient o70) coupled with a deficit presentation. -
Expanding the Genetic Code Lei Wang and Peter G
Reviews P. G. Schultz and L. Wang Protein Science Expanding the Genetic Code Lei Wang and Peter G. Schultz* Keywords: amino acids · genetic code · protein chemistry Angewandte Chemie 34 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/anie.200460627 Angew. Chem. Int. Ed. 2005, 44,34–66 Angewandte Protein Science Chemie Although chemists can synthesize virtually any small organic molecule, our From the Contents ability to rationally manipulate the structures of proteins is quite limited, despite their involvement in virtually every life process. For most proteins, 1. Introduction 35 modifications are largely restricted to substitutions among the common 20 2. Chemical Approaches 35 amino acids. Herein we describe recent advances that make it possible to add new building blocks to the genetic codes of both prokaryotic and 3. In Vitro Biosynthetic eukaryotic organisms. Over 30 novel amino acids have been genetically Approaches to Protein encoded in response to unique triplet and quadruplet codons including Mutagenesis 39 fluorescent, photoreactive, and redox-active amino acids, glycosylated 4. In Vivo Protein amino acids, and amino acids with keto, azido, acetylenic, and heavy-atom- Mutagenesis 43 containing side chains. By removing the limitations imposed by the existing 20 amino acid code, it should be possible to generate proteins and perhaps 5. An Expanded Code 46 entire organisms with new or enhanced properties. 6. Outlook 61 1. Introduction The genetic codes of all known organisms specify the same functional roles to amino acid residues in proteins. Selectivity 20 amino acid building blocks. These building blocks contain a depends on the number and reactivity (dependent on both limited number of functional groups including carboxylic steric and electronic factors) of a particular amino acid side acids and amides, a thiol and thiol ether, alcohols, basic chain. -
Why Are Frameshift Homologs Widespread Within and Across Species?
bioRxiv preprint doi: https://doi.org/10.1101/067736; this version posted August 25, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The shiftability of the protein coding genes 1 Why are frameshift homologs widespread within and across species? 2 Xiaolong Wang*1, Quanjiang Dong2, Gang Chen1, Jianye Zhang1, Yongqiang Liu1, Jinqiao 3 Zhao1, Haibo Peng1, Yalei Wang1, Yujia Cai1, Xuxiang Wang1, Chao Yang1 4 1. College of Life Sciences, Ocean University of China, Qingdao, 266003, P. R. China 5 2. Qingdao Municipal Hospital, Qingdao, Shandong, 266003, P. R. China 6 Abstract 7 Frameshifted coding genes presumably yield truncated and dysfunctional proteins. 8 We report that frameshift homologs, including frameshift orthologs and frameshift 9 paralogs, are actually widespread within and across species. We proposed that protein 10 coding genes have a ca-0.5 quasi-constant shiftability: given any protein coding 11 sequence, at least 50% of the amino acids remain conserved in a frameshifted protein 12 sequence. In the natural genetic code, amino acid pairs assigned to frameshift codon 13 substitutions are more conserved than those to random codon substitutions, and the 14 frameshift tolerating ability of the natural genetic code ranks among the best 6% of all 15 compatible genetic codes. Hence, the shiftability of protein coding genes was mainly 16 predefined by the standard genetic code, while additional sequence-level shiftability 17 was achieved through biased usages of codons and codon pairs. We concluded that 18 during early evolution the genetic code was symmetrically optimized for tolerate 19 frameshifts, so that protein coding genes were endowed an inherent ability to tolerate 20 frameshifting in both forward and backward directions.