genes and mutations

GENES AND MUTATIONS

Dr Prajnya Ranganath,

Asst Professor, Medical Genetics, NIMS

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

FLOW OF INFORMATION: GENE PROTEIN

Proteins do most of the work in the cell.

Information does not flow in the other direction.

RNA

Ribonucleic acid

Like DNA, RNA is made

up of subunits called

nucleotides which are

made of three parts:

Sugar (ribose)

Phosphate

Nitrogen Base

RNA

RNA is single-stranded

Nitrogen bases in RNA:

Adenine (A)

Cytosine (C)

Guanine (G)

Uracil (U) (instead of

thymine)

RNA

There are 3 types of RNA:

Messenger RNA : mRNA

Ribosomal RNA: rRNA

Transfer RNA: tRNA

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.

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.

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.

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

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

TRANSLATION

Translation: process by which proteins are produced

from mRNA

STEPS OF TRANSLATION

mRNA leaves nucleus and binds to a ribosome in

cytoplasm/ rough endoplasmic reticulum (RER)

5’ end of mRNA binds to ribosome

STEPS OF TRANSLATION

Ribosome:

Has 2 subunits & 3 grooves(A, P, E) A: tRNA binding site

P: polypeptite bonding site

E: exit site

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

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

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.

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.

GENETIC CODE

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

MUTATION

Chromosome abnormalities: Alteration in number

Alteration in structure

Different cell lines

Gene mutations: Point Mutation

Deletion

Duplication

Insertion

Inversion

Trinucleotide repeat expansion

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])

CHROMOSOMAL ANOMALIES

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

CHROMOSOMAL ANOMALIES

CHROMOSOMAL ANOMALIES

CHROMOSOMAL ANOMALIES

CHROMOSOMAL ANOMALIES

GENE MUTATIONS

Types of gene mutations:

Point Mutation/ substitution: transition / transversion

Inversion

Deletion

Duplication with/ without frameshift

Insertion

Trinucleotide repeat expansion

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

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

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

GENE MUTATIONS

Normal gene

GGTCTCCTCACGCCA

↓

CCAGAGGAGUGCGGU

Codons

↓

Pro-Glu-Glu-Cys-Gly

Amino acids

Substitution mutation

GGTCTCCTCACTCCA

↓

CCAGAAGAGUGAGGU

↓

Pro-Glu-Glu-STOP

Nonsense mutation

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

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

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

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

GENE MUTATIONS

Trinucleotide repeat expansions: increase in the

number of three nucleotide repeats

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.

Thank You