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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
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