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GENES AND MUTATIONS
Dr Prajnya Ranganath,
Asst Professor, Medical Genetics, NIMS
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GENE DEFINITION
Basic molecular unit of
heredity in a living organism
Portion of DNA which codes
for a specific protein/
polypeptide/ RNA
A locatable region of
genomic sequence,
corresponding to a unit of
inheritance
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FLOW OF INFORMATION: GENE PROTEIN
Proteins do most of the work in the cell.
Information does not flow in the other direction.
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RNA
Ribonucleic acid
Like DNA, RNA is made
up of subunits called
nucleotides which are
made of three parts:
Sugar (ribose)
Phosphate
Nitrogen Base
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RNA
RNA is single-stranded
Nitrogen bases in RNA:
Adenine (A)
Cytosine (C)
Guanine (G)
Uracil (U) (instead of
thymine)
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RNA
There are 3 types of RNA:
Messenger RNA : mRNA
Ribosomal RNA: rRNA
Transfer RNA: tRNA
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TRANSCRIPTION
Transcription: process by which RNA is synthesized
from a DNA template.
Results in flow of information from DNA RNA.
Takes place in cell nucleus.
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STEPS OF TRANSCRIPTION
An enzyme attaches to the promoter (start signal
region) of a gene and unwinds the DNA.
One strand acts as a template.
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STEPS OF TRANSCRIPTION
mRNA copy is made from the DNA template strand by
RNA polymerase.
mRNA copy is synthesized until it reaches the
termination (stop signal) sequence.
The two strands of DNA rejoin.
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POST-TRANSCRIPTION
RNA synthesized during
transcription in the nucleus:
pre mRNA
Before RNA leaves the
nucleus, introns are removed
and exons are joined
together: Splicing
Introns: non coding portions
Exons: coding regions of the
gene
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POST-TRANSCRIPTION
A cap and poly A tail are added to ends of the mRNA sequence
After splicing and addition of cap & polyA tail, pre mRNA mature mRNA
mRNA leaves the nucleus through the nuclear pores
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TRANSLATION
Translation: process by which proteins are produced
from mRNA
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STEPS OF TRANSLATION
mRNA leaves nucleus and binds to a ribosome in
cytoplasm/ rough endoplasmic reticulum (RER)
5’ end of mRNA binds to ribosome
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STEPS OF TRANSLATION
Ribosome:
Has 2 subunits & 3 grooves(A, P, E) A: tRNA binding site
P: polypeptite bonding site
E: exit site
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STEPS OF TRANSLATION
AUG: start codon – from
where translation starts
Each amino acid is attached
to 1 tRNA molecule and is
brought over to mRNA on
the ribosome.
Each tRNA molecule has a
specific anticodon that
matches the codon on the
mRNA strand
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STEPS OF TRANSLATION
tRNA binds to the mRNA sequence and adds an amino
acid
tRNA leaves and amino acids bond together through a
polypeptide bond
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STEPS OF TRANSLATION
Translation of mRNA sequence continues until a stop
codon is reached: Termination
The amino acids then disconnect from the mRNA
sequence and a protein is formed.
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GENETIC CODE
Each group of 3 nucleotides on the mRNA is a codon.
Since there are 4 bases, there are 43 = 64 possible codons, which code for 20 different amino acids.
Most amino acids are coded for by more than one codon i.e. the genetic code is “degenerate”.
AUG is used as the start codon: all proteins are initially translated with methionine in the first position, although it is often removed after translation
There are 3 stop codons, also called “nonsense” codons. Proteins end in a stop codon, which codes for no amino acid.
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GENETIC CODE
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MUTATION
Mutation is a randomly derived, heritable change to the nucleotide sequence of the genetic material of an organism.
Mutations result from:
i. errors in DNA replication
ii. DNA damage due to exposure to mutagens (ultraviolet or ionizing radiation/ mutagenic chemicals/ viruses)
iii. cellular processes such as hypermutation
All mutations do not cause disease
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MUTATION
Chromosome abnormalities: Alteration in number
Alteration in structure
Different cell lines
Gene mutations: Point Mutation
Deletion
Duplication
Insertion
Inversion
Trinucleotide repeat expansion
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CHROMOSOMAL ANOMALIES
1. Alterations in the number of chromosomes:
Polyploidy: multiples of the haploid number Triploidy (69); Tetraploidy (92)
Aneuploidy: loss or gain of 1 or more chromosomes
Monosomy: loss of 1 chromosome eg. 45,X
Trisomy: gain of 1 chromosome eg. 47,XX,+21
Tetrasomy: gain of 2 chromosomes eg. 48,XXXX
2. Different cell lines (mixoploidy):
Mosaicism (45,X [16]/ 46,XX [34])
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CHROMOSOMAL ANOMALIES
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CHROMOSOMAL MUTATIONS
3. Structural alterations: balanced or unbalanced
Inversions:
Pericentric – inversion about the centromere
Paracentric – inversion not involving the centromere
Deletions
Duplications
Translocations:
Reciprocal/ non-reciprocal
Robertsonian
Ring chromosome
Isochromosome
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CHROMOSOMAL ANOMALIES
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CHROMOSOMAL ANOMALIES
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CHROMOSOMAL ANOMALIES
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CHROMOSOMAL ANOMALIES
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GENE MUTATIONS
Types of gene mutations:
Point Mutation/ substitution: transition / transversion
Inversion
Deletion
Duplication with/ without frameshift
Insertion
Trinucleotide repeat expansion
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GENE MUTATIONS
Substitution: change in just one base pair
Synonymous mutation: no change in amino acid
Missense mutation: one amino acid is replaced by
another amino acid
Nonsense mutation: creates a stop codon
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GENE MUTATIONS
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTTCTCACGCCA
↓
CCAGAAGAGUGCGGU
↓
Pro-Glu-Glu-Cys-Gly
Synonymous mutation
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GENE MUTATIONS
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCACCTCACGCCA
↓
CCAGUGGAGUGCGGU
↓
Pro-Arg-Glu-Cys-Gly
Missense mutation
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GENE MUTATIONS
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Substitution mutation
GGTCTCCTCACTCCA
↓
CCAGAAGAGUGAGGU
↓
Pro-Glu-Glu-STOP
Nonsense mutation
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GENE MUTATIONS
Inversion mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Inversion mutation
GGTCCTCTCACGCCA
↓
CCAGGAGAGUGCGGU
↓
Pro-Gly-Glu-Cys-Gly
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GENE MUTATIONS
Insertion mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Insertion mutation
GGTGCTCCTCACGCCA
↓
CCACGAGGAGUGCGGU
↓
Pro-Arg-Gly-Val-Arg
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GENE MUTATIONS
Deletion mutation
Normal gene
GGTCTCCTCACGCCA
↓
CCAGAGGAGUGCGGU
Codons
↓
Pro-Glu-Glu-Cys-Gly
Amino acids
Deletion mutation
GGTC/CCTCACGCCA
↓
CCAGGGAGUGCGGU
↓
Pro-Gly-Ser-Ala-Val
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GENE MUTATIONS
Frame shifting mutation:
causes the reading frame
to shift to left or right
Insertion: addition of 1
or more nucleotides
Deletion: removal of 1
or more nucleotides
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GENE MUTATIONS
Trinucleotide repeat expansions: increase in the
number of three nucleotide repeats
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GENE MUTATIONS
Different genetic disorders are associated with different
types of mutations in different genes.
Same disease can occur because of different types of
mutations in the same gene.
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Thank You