Molecular Biology in Medicine.2014

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    MOLECULARBIOLOGY IN

    MEDICINEA. A. Osuntoki, Ph.D.

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    Molecular biology involves the study of DNA andRNA, the role of these molecules in biological

    systems and how interaction(s) with othermolecules and / or environmental factors affecttheir function.

    The primary role of DNA is to carry genetic

    information. There are various forms of RNA and they have

    various roles in protein synthesis.

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    WHAT IS GENETICS ?

    The study of heredity and variations.

    The study of how characteristics are

    passed from parents to offspring.Also studies how new traits arise.

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    GENETICS AND CLINICAL PRACTICE

    Genetic variation is linked to many humandiseases.

    Some 4000 genetic diseases have been identified

    Genetics is becoming an integral part of healthcare in all medical specialties.

    Clinician are at the interface of science and care

    Lack of genetic training is a common problem forhealth professionals.

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    Knowledge of genome structure and

    function coupled with advances in DNAtechnology are aiding the development ofnovel diagnostic and treatment strategies.

    There is a need to understand the basics

    as genome technologies move from thebench to the clinic.

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    THE CHROMOSOME

    A nucleoprotein complex

    Contains the genetic material

    Polygenic Consists of DNA and basic proteins

    The protein kind and types may vary in

    different cell types Twenty three (23) pairs in humans

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    THE GENE

    Contained on the chromosome

    The unit of heredity

    Finite sequence of nucleotides

    In eukaryotes, each cell contains the full genetic complement

    (exception: mature rbc)

    Made up of DNA in most life forms

    Contains information for the blueprint for the organism

    Sequence of DNA capable of independent expression

    The major function is to specify the sequence of amino acids in aprotein

    Determines the structure of a protein

    Must be expressed to perform its biological roles.

    Specific genes determine hereditary traits

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    DEOXYRIBONUCLEIC ACID (DNA)

    Is the store of genetic information in all life forms exceptsome viruses where RNA is the genetic material

    Double stranded helix

    The two strands are anti-parallel The structure is stabilized by hydrogen bonds between

    base pairs (AT, GC)

    The double stranded chain structure ensuresinformation retrieval in case of damage to a strand.

    In the cell DNA serves as a template for its ownreplication and as a template for RNA synthesis.

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    BASE PAIRING IN DNA

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    DNA STRUCTURE

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    THE GENETIC CODE

    Genetic information is organized into genes or cistrons

    The message is encoded in a triplet of bases called codons

    Codons specify the amino acids to be incorporated into agrowing protein chain

    Codons also specify chain termination

    There are 64 codons

    61 codons specify amino acids

    3 codons specify chain termination

    The code is degenerate The code is universal

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    RIBONUCLEIC ACID(RNA)

    A close chemical relative of DNA.

    The major difference is the absence of oxygenat the 2Iposition of the sugar-phosphate

    backbone of DNA which is present in RNA. RNA is single stranded while DNA is double

    stranded.

    Present in several different forms in living cells

    * messenger RNA (mRNA)* transfer RNA (tRNA)

    * ribosomal RNA (rRNA)

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    GENE EXPRESSION

    A gene is said to be expressed when the

    gene product is being produced.

    The flow of genetic information is depicted

    below:

    DNA RNA PROTEIN

    i ii

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    The implication is that DNA makes RNA which in turn makesproteins.

    This is what is generally referred to as the Central dogma ofgene expression.

    The formation of daughter DNA strands is called replication.This process is semiconservative i.e. a strand in a new pairis newly formed while the other is inherited.

    The transfer of genetic information to RNA (i) is calledtranscription. All RNA types are transcribed from DNA.

    The conversion of the genetic information into a polypeptide(ii) is called translation.

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    REPLICATION

    Replication is semiconservative.

    Starts at a unique origin and proceeds inopposite directions.

    Both strands serve as templates. DNA synthesis is primed by RNA.

    One strand is synthesized discontinuously.

    DNA polymerase takes instruction from the

    template. DNA polymerase corrects mistakes during

    replication.

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    TRANSCRIPTION

    Only one strand of DNA is transcribed in aparticular region of the genome.

    Direction of synthesis is 51 31like that of DNA.

    Transcription is initiated at promoter sites on theDNA template.

    RNA polymerase takes instructions from a DNAtemplate.

    Many RNA molecules undergo post-transcriptional modifications.

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    TRANSLATION

    The conversion of the information in a gene intoa protein molecule.

    The process of reading the genetic code.

    Takes place in the ribosome. mRNA is the template.

    The tRNAs carry amino acids in the activatedform to the ribosome for incorporation into a

    nascent chain. AUG is the start codon while UUA, UAG and

    UGA are stop codons.

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    PHENOTYPES ANDGENOTYPES

    Phenotypes : All the observablecharacteristics of an individual

    Traits: refer to the single characteristic of the

    individual

    Genotypes: The genes that make up thechromosomes showing a characteristic trait

    Genes contain the actual code for traits Alleles: variations of a gene that relate to the

    same characteristic are called alleles

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    GENETIC DISORDERS

    Genetic disorders can result from:

    Abnormal chromosome numbers Changes in the reading frame caused by

    deletions and insertion

    Changes in nucleotide sequence

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    MUTATION ANDDISEASES

    The information carrying function of DNArequires the protection of the integrity of themolecule.

    It is apparent that faithful transmission(copying) of the information at eachgeneration is essential for preserving the

    characteristics of organisms..

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    Mutation contd

    A nucleotide sequence alteration may

    change the composition of nucleotides in a

    codon, or affect the way the gene is read.This may result in the incorporation of an

    incorrect amino acid into the protein .

    A mutation may have significant effects on

    the organism or may be harmless

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    mutation contd..

    An altered amino acid sequence may greatly affect the abilityof the protein to perform its biological role.

    The chemical and physical features (including the structure)of a protein result from the arrangement and composition of

    amino acids in the chain. The function of biological molecules is intrinsically linked to

    the structure. Thus, the replacement of even a single aminoacid with another may diminish the capacity of a protein tofunction or inactivate it.

    The end results are genetic defects which may manifest withnegative impacts on the health of individuals.

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    Alterations in the nucleotide sequence results inmutation

    There are two broad classifications of mutation- Point mutation (single base substitution)

    - Frame shift mutation (indel)

    Mutation contd

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    If one purine [A or G] or pyrimidine [C or T] is replaced by theother, the substitution is called a transition

    If a purine is replaced by a pyrimidine or vice-versa, the

    substitution is called a transversion

    Samesense: The mutation results in the formation of a codonthat is a synonym of the wild type

    Missense:The mutation alters the codon to produce an

    altered amino acid in the protein product Nonsense: The mutation changes a codon for an amino acid

    into a stop codon

    POINT MUTATION

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    Insertion

    Deletion

    FRAMESHIFT MUTATION

  • 8/21/2019 Molecular Biol

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