DOCSLIB.ORG

Understanding Genetics (Booklet)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Understanding Genetics (Booklet) PROVIDING THE LATEST INFORMATION FOR PATIENTS & CAREGIVERS Understanding Genetics Revised 2020 Support for this publication provided by A six-word narrative about living with blood cancer from patients in our LLS Community Stay strong and keep moving forward. Find the positive in every day. Be your own best patient advocate. Changed my life for the better. Accept, learn and focus on present. Learning to live a different life. Sudden and life changing—be positive. Waiting, worrying, anxiousness/ happy I’m alive! Embrace a new normal each day. 5 years, 41 infusions, constant fatigue. Patience, positive attitude, hope and faith. Test to test, I will survive! Treatment, fatigue, treatment, fatigue and survival. Love life, live better every day. I don’t look back only forward. So far, so good, live life. Meditation, mindfulness, wellness, faith, nutrition and optimism. Finding the joy while living with uncertainty. Watch, wait, treat, regroup, rest, re-energize. Blessed to be doing so well! Eye opening needed learning and healing. Feel great: uncertain travel plans annoying. Renewed faith, meditation, diet, mindfulness, gratitude. Watchful waiting can be watchful worrying. Scary, expensive, grateful, blessings, hope, faith. Thank god for stem cell transplants! Do not know what to expect. Extraordinarily grateful, I love my life. Diagnosed; frightened; tested; treating; waiting; hoping. I’m more generous, impatient less often. Embrace your treatment day after day. Live today, accept tomorrow, forget yesterday. Strength you never realized you had. Challenging to our hearts and minds. Life is what we make it. Live life in a beautiful way. Discover what thousands already have at www.LLS.org/Community Join our online social network for people who are living with or supporting someone who has a blood cancer. Members will find: • Thousands of patients and caregivers sharing experiences and information, with support from knowledgeable staff • Accurate and cutting-edge disease updates • The opportunity to participate in surveys that will help improve care Inside This Booklet 2 Introduction 4 Cells 4 Chromosomes 6 DNA (deoxyribonucleic acid) 7 Genes 7 Mutations 15 The Genetics of Cancer 15 Types of Testing for Mutations in Cancer Cells 17 Precision Medicine 18 Research and Clinical Trials 19 Resources and Information 22 Other Resources 23 Health Terms Acknowledgement The Leukemia & Lymphoma Society (LLS) appreciates the review of this material by Patrick T. Fueger, MS, PhD Associate Professor, Department of Molecular & Cellular Endocrinology Director, Comprehensive Metabolic Phenotyping Core Beckman Research Institute City of Hope Duarte, CA This publication is designed to provide accurate and authoritative information about the subject matter covered. It is distributed as a public service by LLS, with the understanding that LLS is not engaged in rendering medical or other professional services. Introduction Cancer is a disease that is caused by abnormal changes (mutations) to the genetic material inside of cells. This genetic material is called DNA (deoxyribonucleic acid). When cells divide to create new cells, the DNA is passed to the new cells. Therefore, mutated DNA may cause the new cells to develop into cancer cells. Cancer cells behave differently than normal cells. They multiply uncontrollably even though they are not needed in the body, and evade the immune system. DNA damage and mutations happen more commonly than one might think but the immune system usually identifies these abnormal cells and eliminates them. Some of these abnormal cells that avoid immune detection go on to become cancerous cells. These cancer cells can spread to surrounding areas and form tumors. The cancer cells can build up in the blood, the bone marrow (the spongelike tissue in the center of most bones), the lymph nodes and other areas of the body. Genetics and Genomics. Each person’s cancer has a unique combination of genetic mutations. Genetic materials are examined in two different, but complementary, fields of study, namely genetics and genomics. “Genetics” is the study of genes and their roles in inheritance—the ways in which traits or conditions are passed down from one generation to the next. “Genomics” is the study of the complete set of DNA of a person’s genome; the genome is made up of all of a person’s genes. Genomics also examines how the genes interact with each other and how, or if, they are affected by environmental factors. Researchers are learning that the genetic changes that occur in one person’s cancer may not occur in other people who have the same type of cancer. Specific information about a person’s own genes and/or proteins is used to prevent, diagnose, or treat cancer in an approach to a type of care known as “precision medicine.” Genetic and genomic testing provides doctors with the individualized information (based on specific genetic changes and the genomic makeup of abnormalities within the cancer tissue) that they need to develop specific targeted treatments for their patients. { Genetic testing: These tests examine changes in an individual gene and/or set of genes that may account for the likelihood of a particular disease process; however, a test may not pick up every change in a gene. This type of information is useful if a particular drug is known to work for certain gene/protein variants. It allows for targeted therapies (for example, Tibsovo® [ivosidenib], which is approved for treatment of acute myeloid leukemia in patients who have an IDH1 gene mutation). 2 I 800.955.4572 I www.LLS.org { Genomic testing: These tests assess an individual’s genome (all of a person’s genes, rather than a specific gene or set of genes). The scope of genomic testing includes gene alterations (mutations) and/or harmful changes in the genetic code—however they are caused. Researchers hope that, one day, testing cancer cells for mutations this way will help doctors match each patient with the most effective treatment for his or her disease. Cells, Chromosomes, and DNA Human Cell Nucleus DNA Chromosome A T Base © Fran Milner 2020 pairs C G Highlights. In this booklet you will learn that { The human body is made up of trillions of cells. { In almost every cell, there is a nucleus that contains your genome (all of your genetic material), which is essentially a blueprint for your body to develop and grow. { In the nucleus of most cells, your genetic material is packaged into thread like structures called “chromosomes.” { Chromosomes are made of DNA (deoxyribonucleic acid) that is wrapped around specialized proteins called “histones.” { DNA is the hereditary material that passes from one generation to the next. Nearly every cell in your body has the same DNA. { Cancer is a disease that is caused by abnormal changes (mutations) to the genetic material inside of cells. Understanding Genetics I 3 { Each person’s cancer has a unique combination of genetic mutations. Precision medicine is an important approach to patient care that allows doctors to select treatments that are tailored to specific genetic changes of each person’s cancer. Feedback. Visit www.LLS.org/PublicationFeedback to give suggestions about this booklet. Cells Cells are considered the basic units of life. The human body is made up of trillions of cells that carry out essential functions allowing the body to survive. Each type of cell plays a specific role in the body. For example, red blood cells carry oxygen throughout your body; nerve cells send electrical messages that create thoughts and movement; and heart cells contract to pump blood. Cells also make products that your body needs such as sweat, saliva, and hormones. In almost every cell, there is a nucleus that contains your genome (all of your genetic material). Your genome is essentially a blueprint for your body to develop and grow. Chromosomes In the nucleus of most cells, your genetic material is packaged into threadlike structures called “chromosomes.” Human cells normally contain 23 pairs of chromosomes, for a total of 46 chromosomes. Chromosomes are passed from the parents to a child. You inherit 23 chromosomes from your mother’s egg cell, and you inherit the other 23 chromosomes from your father’s sperm cell. Under the microscope, you can see that chromosomes come in different lengths and striping patterns. The first 22 of these pairs are called “autosomes,” and they are the same in males and females. The 23rd pair is the sex chromosomes; female and male sex chromosomes are different. Females have two copies of the X chromosome, whereas males have one X chromosome and one Y chromosome. Somewhere between one-third and two-thirds of the way down the chromosome is the centromere, p arm a narrow region that divides the chromosome into Centromere two sections, or “arms.” The short arm of the chromosome is called the “p arm,” and the long arm q arm of the chromosome is called the “q arm.” Geneticists use the names of the arms to describe the position of a specific section of the chromosome. For example, 13q describes the long arm of chromosome 13, while 17p describes the short arm of chromosome 17. © Fran Milner 2020 4 I 800.955.4572 I www.LLS.org This image of normal human chromosomes lined up in pairs is called a “karyotype.” KaryotypeKaryotypeKaryotypeKaryotypeKaryotypeKaryotype FromFromFrom FrommotherFromFrom mother mother mothermother mother p arm (egg)(egg)(egg)(egg)(egg)(egg) p armp armppp p arm armarm arm CentromereCentromereCentromereCentromereCentromereCentromere FromFromFrom FromfatherFromFrom father father father father father (sperm)(sperm)(sperm)(sperm)(sperm)(sperm) q armq armqqq q arm armarm arm 1 1 1111 2 2 2222 3 3 3333 4 4 4444 5 5 5555 6 6 6666 7 7 7777 8 8 8888 9 9 9999 10 1010101010 11 11 11111111 12 1212121212 13 13 13131313 14 14 14141414 15 1515151515 16 1616161616 17 17 17171717 18 1818181818 19 1919191919 202020202020 21 2121212121 222222222222 XXXX (Female)XXXX XX(Female)XX (Female) (Female)(Female) (Female)XYXY (Male)XYXY XY(XYMale) ( (Male)(Male) Male)(Male) © Fran Milner 2020 © Fran© FranMilner©©© Fran ©Fran MilnerFran 2020Fran Milner Milner Milner 2020Milner 2020 2020 2020 2020 Understanding Genetics I 5 DNA (deoxyribonucleic acid) Chromosomes are made of DNA.
Load more

Recommended publications
  • 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.
    [Show full text]
  • 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).
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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
    [Show full text]
  • Genetics of Sma
    CURE SMA CARE SERIES BOOKLET A SOURCE OF INFORMATION AND SUPPORT FOR INDIVIDUALS LIVING WITH SPINAL MUSCULAR ATROPHY AND THEIR FAMILIES. GENETICS OF SMA 1 SMA AND GENETICS Spinal muscular atrophy (SMA) is often referred to by several terms, including “genetic disease,” ‘’autosomal recessive genetic disorder,” “motor-neuron disease,” or ‘’neuromuscular disease.” SMA is a genetic disease. “Genetic” means it is relating to the genes and is inherited. Genes are responsible for our traits and unique characteristics. In SMA, there is a mutation in a gene responsible for the survival motor neuron (SMN) protein, a protein that is critical to the function of the nerves that control normal muscle movements. SMA is an autosomal recessive genetic disorder. “Autosomal recessive” refers to how the disease is inherited, or passed down, from the parents to the child. In SMA, the individual who is affected by SMA inherits two copies of a non-working gene—one copy from each parent. SMA is a motor-neuron disease. “Motor-neuron” refers to the type of nerve cell that sends messages to and from muscles responsible for movement and control of the head, neck, chest, abdomen, legs, and limbs. In SMA, the motor-neurons in the spinal cord do not have enough SMN protein. As a result, these motor-neurons do not function normally and may die, resulting in muscle weakness and atrophy (shrinkage). SMA is a neuromuscular disease. A “neuromuscular disease” affects the neuromuscular system. This can include problems with the nerves that control muscles, the muscles, and the communication between the nerves and the muscles.
    [Show full text]
  • Understanding the Introduction of Genetic Variations by Random
    Understanding the Introduction of Genetic Variations by Random Mutation Lesson Overview The focus of this lesson is on mutations as a source of genetic variability and what it means to say that mutations occur randomly at a particular rate. Students will make predictions about and observe the random mutations in the genomes of Avidians. Big Ideas The basic components of the Darwinian evolutionary mechanism are variation, inheritance, natural selection and time (aka VIST). Genetic variation is produced by mutations—changes in an organism’s genome caused by random replication errors. These errors occur at a relatively constant rate within broad groups of organisms and may be expressed probabilistically in various ways (e.g. mutation rate per base pair or per genome per replication).1 Because each site in the genome is equally susceptible to replication errors, the actual number of mutations occurring during a given replication event is variable, with higher mutation rates increasing the likelihood that mutations will occur. Random mutations produce the raw materials that are shaped by non-random selection into complex adaptive features. Objectives for Student Learning Through engagement in this lesson, students will: • Learn that mutations may occur at random in a genome at various rates • Observe how random mutations introduce genotypic variability in a population • Explain what mutation rates imply about the distribution of genotypic changes • Test hypotheses via a cycle of Hypothesis, Prediction, Testing, and Evaluation. Students’ Prior Knowledge Students should have a basic understanding of probability. However, they may struggle with what is meant by a particular mutation rate. Students may think, for instance, that a 10% mutation rate means that that there will always be a 10% difference between the ancestor and offspring, instead of recognizing that each site in the genome independently has a 10% chance of changing during replication.
    [Show full text]
  • Code Cracking Mutation Practice
    Name: ___________________________________________ Date: __________________ Period: _____ Code Cracking Mutation Practice Review: Three of the most common types of mutations are: 1. POINT MUTATION (one base is substituted for another) If a point mutation changes the amino acid, it’s called a MISSENSE mutation. If a point mutation does not change the amino acid, it’s called a SILENT mutation. If a point mutation changes the amino acid to a “stop,” it’s called a NONSENSE mutation. 2. INSERTION (an extra base, or bases, is inserted) 3. DELETION (a base, or bases, is lost) Deletion and insertion may cause what’s called a FRAMESHIFT, meaning the reading frame changes. These are typically one of the most serious types of mutations. Directions: 1. Following the same procedure you followed during the decoding activity (DNA to mRNA to Amino Acid), decode the original and mutated sequences and identify them as one of the three types of mutations listed above. If it is a point mutations, include whether it is a missense, silent, or nonsense mutations. The original DNA sequence is: DNA: TGC GTG CTT AAG CGG TGT ACA CGT TGC mRNA: Amino acid: Symbol: Now decode the following mutated sequences: 2. TGC GTG CTT AAG CGA TGT ACA CGT TGC What kind of mutation is this? Do you think it will affect the protein’s function? Why? 3. TGC GTG CTT AAG CGG TGT GCA CGT TGC What kind of mutation is this? Do you think it will affect the protein’s function? Why? 4. TGC GTG CTT AAG TAG TGT ACA CGT TGC What kind of mutation is this? Do you think it will affect the protein’s function? Why? 5.
    [Show full text]
  • A Point Mutation Within Exon 5 of the WT1 Gene of a Sporadic Unilateral Wilms' Tumor Alters Gene Function1
    (CANCER RESEARCH 58. 4180-4184. September 15. 1998] A Point Mutation within Exon 5 of the WT1 Gene of a Sporadic Unilateral Wilms' Tumor Alters Gene Function1 Li-Shuang Guan, Jia-jia Liu, Yong-Hua Xu, and Zhao-Yi Wang2 Department of Medicine, Division of Growth Regulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215 ¡L-S.C., Z-Y. W.¡.and Shanghai Institute of Cell Biology, Shanghai, People's Republic of China [J-j. L, Y-H. X.¡ ABSTRACT The insertion of three amino acids (+KTS) disrupts the distance between zinc fingers 3 and 4 and thus alters its DNA-binding speci The Wilms' tumor suppressor gene, nil, encodes a zinc-finger tran ficity (6, 7). The NH2 terminus of WT1 contains a proline- and scription factor, WT1, that represses transcription of a number of growth- glutamine-rich domain that exhibited transcription-regulating activity promoting genes and inhibits cell growth. The transcripts of wit undergo in transient cotransfection assays (7, 8) two alternative splicing events, giving rise to four isoforms of mRNA in constant ratios. The first alternative splice introduces an extra exon 5, Consistent with the view that WT1 functions as a tumor suppressor, which encodes 17 amino acid residues inserted between the transcription experimental evidence has demonstrated that WT1 represses tran regulatory domain and the DNA binding domain of WT1. Previously, we scription of a number of growth-related genes. These include, PDGF demonstrated that the 17-amino acid domain functioned as a transcription A-chain, insulin-like growth factor II, epidermal growth factor recep repressor when it was fused with the DNA binding domain of WT1.
    [Show full text]
  • DNA Mutation Worksheetkey
    Name: ________________________ BIO300/CMPSC300 Mutation - Spring 2016 As you know from lecture, there are several types of mutation: DELETION (a base is lost) INSERTION (an extra base is inserted) Deletion and insertion may cause what’s called a FRAMESHIFT, meaning the reading “frame” changes, changing the amino acid sequence. POINT MUTATION (one base is substituted for another) If a point mutation changes the amino acid, it’s called a MISSENSE mutation. If a point mutation does not change the amino acid, it’s called a SILENT mutation. If a point mutation changes the amino acid to a “stop,” it’s called a NONSENSE mutation. Complete the boxes below. Classify each as either Deletion, Insertion, or Substitution AND as either frameshift, missense, silent or nonsense (hint: deletion or insertion will always be frameshift). Original DNA Sequence: T A C A C C T T G G C G A C G A C T mRNA Sequence: A U G U G G A A C C G C U G C U G A Amino Acid Sequence: MET -TRP- ASN - ARG- CYS - (STOP) Mutated DNA Sequence #1: T A C A T C T T G G C G A C G A C T What’s the mRNA sequence? A U G U A G A A C C G C U G C U G A What will be the amino acid sequence? MET -(STOP) Will there likely be effects? YES What kind of mutation is this? POINT MUTATION- NONSENSE Mutated DNA Sequence #2: T A C G A C C T T G G C G A C G A C T What’s the mRNA sequence? A U G C U G G A A C C G C U G C U G A What will be the amino acid sequence? MET - LEU -GLU– PRO-LEU-LEU Will there likely be effects? YES What kind of mutation is this? INSERTION - FRAME SHIFT Mutated DNA Sequence
    [Show full text]
  • Point Mutation Specific Antibodies in B-Cell and T-Cell Lymphomas And
    diagnostics Review Point Mutation Specific Antibodies in B-Cell and T-Cell Lymphomas and Leukemias: Targeting IDH2, KRAS, BRAF and Other Biomarkers RHOA, IRF8, MYD88, ID3, NRAS, SF3B1 and EZH2 Kunwar Singh 1,*,† , Sumanth Gollapudi 2,† , Sasha Mittal 2, Corinn Small 2, Jyoti Kumar 1 and Robert S. Ohgami 2,* 1 Department of Pathology, Stanford University, Stanford, CA 94063, USA; [email protected] 2 Department of Pathology, University of California, San Francisco, CA 94143, USA; [email protected] (S.G.); [email protected] (S.M.); [email protected] (C.S.) * Correspondence: [email protected] (K.S.); [email protected] (R.S.O.); Tel.: +1-347-856-7047 (K.S.); +1-415-514-8179 (R.S.O.) † These authors contributed equally. Abstract: B-cell and T-cell lymphomas and leukemias often have distinct genetic mutations that are diagnostically defining or prognostically significant. A subset of these mutations consists of specific point mutations, which can be evaluated using genetic sequencing approaches or point mutation Citation: Singh, K.; Gollapudi, S.; specific antibodies. Here, we describe genes harboring point mutations relevant to B-cell and T-cell Mittal, S.; Small, C.; Kumar, J.; malignancies and discuss the current availability of these targeted point mutation specific antibodies. Ohgami, R.S. Point Mutation Specific We also evaluate the possibility of generating novel antibodies against known point mutations Antibodies in B-Cell and T-Cell by computationally assessing for chemical and structural features as well as epitope antigenicity Lymphomas and Leukemias: of these targets. Our results not only summarize several genetic mutations and identify existing Targeting IDH2, KRAS, BRAF and point mutation specific antibodies relevant to hematologic malignancies, but also reveal potential Other Biomarkers RHOA, IRF8, underdeveloped targets which merit further study.
    [Show full text]
  • The Origin of Point Mutations in Human Tumor Cells1 Bernard S
    [CANCER RESEARCH 52. 249-253, January 15. 1992] Perspectivesin CancerResearch The Origin of Point Mutations in Human Tumor Cells1 Bernard S. Strauss2 ICRF Clare Hall Laboratories and Department of Molecular Genetics and Cell Biology, The university of Chicago, Chicago, Illinois 6063 7 The idea that point mutation is central to carcinogenesis is zling since one of the major hypotheses of the 1970s was the an old one (e.g. Ref. l). Until recently, however, specific genetic proposal that carcinogens acted to produce point mutations; changes had not been observed in tumors and a keystone of the that all, or at least the overwhelming majority, of carcinogens belief that genetic change is central to carcinogenesis was what were mutagenic; and that the production of mutations was the appeared to be a close correlation between mutagenicity and mechanism by which carcinogens acted (13). The discovery of carcinogenicity (2). The situation is almost completely reversed transforming oncogenes (14), and particularly the observation today. The class of nonmutagenic carcinogens has been shown by Barbacid et al. (15) that methylnitrosourea-induced breast to be considerable (3). On the other hand, so many genetic tumors in rats were invariably associated with G—»Atransitions changes have been observed in individual cancers that the in the ras oncogene of the tumor, appeared to fulfill one of measured mutation rates in somatic cells seem unable to ac Koch's postulates, that an etiological agent should be invariably count for their appearance. For example, single tumors may associated with the development of disease. Identity of the type contain both ras and p53 point mutations along with chromo of mutation produced in experimental tumors by methylnitro- somal changes (4).
    [Show full text]