DOCSLIB.ORG

Chemical Biology 03! Oct 16, 2009!

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chemical Biology 03! Oct 16, 2009! Chemical Biology 03! Oct 16, 2009! Central Dogma –III! and mutation! Transcription temporary intermediate (“messenger”) Translation plasm! cyto flow of information in ALL cellular organisms = “the Central Dogma” in Eukaryotes 1o transcript (“pre-mRNA”) Processing of messenger RNA • at the 5’ end • at the 3’end • in the middle mature mRNA ready for translation CAP is added to 5’ end and TAIL is added to 3’ end of each mRNA mRNA! 5’! 3’! Necessary for message stability And identification as a messenger RNA! "#$! %&'()*&+,%+-(! ,&-%.+(!%&'()/'%+-(! introns intervening sequences Splicing expressed sequences - remove introns exons - rejoin exons protein translation β Globin primary transcript is 2000 nucleotides long ! Splicing protein translation β Globin polypeptide is 147 amino acids long Arrangement of exons and introns in two human blood genes in Eukaryotes 1o transcript (“pre-mRNA”) Processing of messenger RNA • at the 5’ end • at the 3’end • in the middle mature mRNA ready for translation Ribosome = Protein Factory last week’s Nobel Prize (Chem): studies that unveiled the structure &function amino acids are assembled of the ribosome: according to order specified by Venkatraman Ramakrishnan (UK), messenger RNA Tom Steitz (U.S.), Ada Yonath (Israel) Ribosome is enormous (complex of >80 proteins & 4 RNA molecules) Typical cell has millions of ribosomes! Adapter Molecules make the correlation between codon and amino acid: tRNA (transfer RNA) tRNA ! #0! 01! #0! 01! #0! 01! ”reads” codon (triplet of nucleotides in mRNA)! .%*5! 23#$4!!!A-U-G - C-U-G -G-U-G-G-A-U-C-C-U-G-G-A-U-U-C tRNA (transfer RNA) ~80 nte single stranded RNA molecule '(%+*-8-(! 67! -UCGGUAACUUGUACACC- 97! !"#$% *-8-(! The GENETIC CODE to Translate from RNA to PROTEIN: triplet code: set of 3 nucleotides (“codon”) encodes 1 amino acid ! ! ! !:2,-&%'(*.!-;!3.'8+(<!=&'2.! %A.!*'%!'%.!%A.!B@<! <.(.%+*!*-8.!+)!#>?!,@(*%@'%.8 !%A.*'%'%.%A.B@<! %!A.*!'%'!%.%!A.B!@<! ! ! ! ! ! ! ! !! %A!.*'!%'%!.%A!.B@!<! #-%.!&!,-))+B/.! &.'8+(<!;&'2.)!;-&!'(F! <+G.(!)%&.%*A!-;!3#$! -(/F!-(.!<+G.)!8.)+&.8!,&-%.+(! C-D!+)!&.'8+(<!;&'2.!*A-).(E! C-D!+)!&.'8+(<!;&'2.!2'+(%'+(.8E! Reading Frame is established by first AUG codon ( = START) 5’-A-C-G-U-A-U-G-C-A-U-U-U-G-A-C-G-U-A-A-3’ “gene” Segment of DNA that encodes a product (includes sequences that Do not directly code for a.a.)! H@I'&F-%.)! Mutation = change to DNA Caused by: errors in DNA Replication toxic chemicals (mutagens) other environmental abuse such as UV rays! How would change to DNA affect a gene product? ! H;;.*%!-;!)+(</.!(@*/.-%+8.!*A'(<.!+(!"#$!!JK!L,-+(%!2@%'%+-(MN4! TAC CGA TTC TTC CAA ATA CGG UAG GCU AAG AAG GUU UAU GCC met--ala--lys--lys---val--tyr---ala O').!P@B)%+%@%+-()! QP+/.( %!2@%'%+-(! TAC CGA TTC TTT CAA ATA CGG UAG GCU AAG AAA GUU UAU GCC met--ala--lys--lys---val--tyr---ala QR+)).().!2@% '%+-(! TAC CGA TTC TGC CAA ATA CGG UAG GCU AAG ACG GUU UAU GCC met--ala--lys---thr---val--tyr---ala Q#-().().!2@% '%+-(! TAC CGA TTC ATC CAA ATA CGG UAG GCU AAG UAG GUU UAU GCC met--ala--lys--stop =&'2.!PA+;%!2@%'%+-()!! J&.*'//!S'(-;)IF7)!D-&IN! TAC CGA TTC TTC CAA ATA CGG UAG GCU AAG AAG GUU UAU GCC "./.%+-()! 2.%00'/'00/F)000/F)000G'/00%F&000'/'! TAC CGA TTC TCC AAA TAC GGA :().&%+-()! UAG GCU AAG AGG UUU AUG CCU 2.%00'/'00/F)00/F)000,A.002.%00,&-! TAC CGA TTC TTT CCA AAT ACG UAG GCU AAG AAA GGU UUA UGC 2.%00'/'00/F)00/F)000</F00/.@000*F)!.
Load more

Recommended publications
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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%).
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Implications of Gene Copy-Number Variation in Health and Diseases
    Journal of Human Genetics (2012) 57, 6–13 & 2012 The Japan Society of Human Genetics All rights reserved 1434-5161/12 $32.00 www.nature.com/jhg REVIEW Implications of gene copy-number variation in health and diseases Suhani H Almal and Harish Padh Inter-individual genomic variations have recently become evident with advances in sequencing techniques and genome-wide array comparative genomic hybridization. Among such variations single nucleotide polymorphisms (SNPs) are widely studied and better defined because of availability of large-scale detection platforms. However, insertion–deletions, inversions, copy-number variations (CNVs) also populate our genomes. The large structural variations (43 Mb) have been known for past 20 years, however, their link to health and disease remain ill-defined. CNVs are defined as the segment of DNA 41 kb in size, and compared with reference genome vary in its copy number. All these types of genomic variations are bound to have vital role in disease susceptibility and drug response. In this review, the discussion is confined to CNVs and their link to health, diseases and drug response. There are several CNVs reported till date, which have important roles in an individual’s susceptibility to several complex and common disorders. This review compiles some of these CNVs and analyzes their involvement in diseases in different populations, analyses available evidence and rationalizes their involvement in the development of disease phenotype. Combined with SNP, additional genomic variations including CNV, will provide better correlations between individual genomic variations and health. Journal of Human Genetics (2012) 57, 6–13; doi:10.1038/jhg.2011.108; published online 29 September 2011 Keywords: CNV; diseases; gene copy number; genetic variants; health; neurodisorders; pharmacogenetics; SNP INTRODUCTION elements.
    [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]
  • The Making of the Fittest: Natural Selection and Adaptation INTRODUCTION to the MOLECULAR GENETICS of the COLOR MUTATIONS IN
    Lesson The Making of theThe Fittest: Making of the Fittest LESSON Natural Selection and Adaptation Educator Materials Natural Selection and Adaptation TEACHER MATERIALS INTRODUCTION TO THE MOLECULAR GENETICS OF THE COLOR MUTATIONS IN ROCK POCKET MICE OVERVIEW These lessons serve as an extension to the Howard Hughes Medical Institute short film The Making of the Fittest: Natural Selection and Adaptation. Students will transcribe and translate portions of the wild-type and mutant rock pocket mouse Mc1r gene. By comparing DNA sequences, students identify the locations and types of mutations responsible for the coat-color change described in the film. Students will answer a series of questions to explain how a change in amino acid sequence affects the functionality of the MC1R protein, and how that change might directly affect the coat color of the rock pocket mouse populations and the survival of that population. KEY CONCEPTS AND LEARNING OBJECTIVES • A mutation is a random change to an organism’s DNA sequence. • Most mutations have no effect on traits, but some mutations affect the expression of a gene and/or the gene product. • The environment contributes to determining whether a mutation is advantageous, deleterious, or neutral. • Natural selection preserves favorable traits. • Variation, selection, and time fuel the process of evolution. • Both the type of the mutation and its location determine whether or not it will have an effect on phenotype (advanced version only). Students will be able to: • transcribe and translate a DNA sequence.
    [Show full text]
  • The Genetics of Autism 6 Deborah K
    The Genetics of Autism 6 Deborah K. Sokol and Debomoy K. Lahiri This chapter is written to make the fast-paced, expand- an affected sibling–pair design in multiplex (having more ing field of the genetics of autism accessible to those than one affected member) families. This led to the identi- practitioners who help children with autism. New genetic fication of chromosomal abnormalities in such conditions as knowledge and technology have quickly developed over neurofibromatosis, tuberous sclerosis, and dyslexia (Smith, the past 30 years, particularly within the past decade, and 2007). Improving technology in the 1990s enabled the detec- have made many optimistic about our ability to explain tion of small genomic alterations of 50–100 kb and the direct autism. Among these advances include the sequencing of visualization of these alterations in uncultured cells via fluo- the human genome (Lander et al., 2001) and the identifi- rescent in situ hybridization (FISH). This technique ushered cation of common genetic variants via the HapMap project in the field of molecular genetics (Li & Andersson, 2009) (International HapMap Consortium, 2005), and the develop- and allowed the identification of chromosomal microdele- ment of cost-efficient genotyping and analysis technologies tions and duplications in areas of the chromosome where (Losh, Sullivan, Trembath, & Piven, 2008). Improvement in there is already high suspicion that abnormality would exist. technology has led to improved visualization of chromoso- FISH enables prenatal and cancer genetics screening and has mal abnormality down to the molecular level. The four most led to the identification of genetic aberrations associated with common syndromes associated with autism include frag- Angelman’s and Prader Willi syndromes.
    [Show full text]
  • Are Synonymous Codons Indeed Synonymous ?
    BioMol Concepts, Vol. 3 (2012), pp. 21–28 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/BMC.2011.050 Review Are synonymous codons indeed synonymous ? P á l Venetianer synonymous codons is related to the species-specifi c con- Biological Research Centre , Hungarian Academy of centrations of isoaccepting tRNAs. It has also been shown Sciences, Temesv á ri krt. 62, H-6726 Szeged , Hungary that within one species (e.g., human), the level of expression of individual genes is correlated with the frequency of opti- mal codons (i.e., codons with the highest tRNA gene copy e-mail: [email protected] number) (7, 8) . Thus codon usage might be optimised in such a way that the frequency of occurrence of any particular codon for each Abstract amino acid is correlated with the abundance of the corre- sponding tRNA molecule. This is not always true, however. In It has long been known that the distribution and frequency a recent review Czech et al. (9) emphasise the importance of of occurence of synonymous codons can vary greatly among the precise assessment of tRNA composition and summarise different species, and that the abundance of isoaccepting the methods applicable for determining the concentrations of tRNA species could also be very different. The interaction tRNA species. If and when such a correlation exists, an obvi- of these two factors may infl uence the rate and effi ciency ous consequence of this fact is that synonymous mutations of protein synthesis and therefore synonymous mutations could lead to a slowdown of protein synthesis. This effect is might infl uence the fi tness of the organism and cannot be often practically exploited in biotechnology where developers treated generally as ‘ neutral ’ in an evolutionary sense.
    [Show full text]