D1.3 Mutations and gene editing

Mutation

change in DNA sequence

Insertion

base is added

Deletion

base is removed

Substitution

base changed for another

Point mutation

only involves change of one base

Single nucleotide polymorphism (SNP)

single subsitution

Sickle cell disease

• substituion

• GAG → GTG

• Changes shape of haemolobin and red blood cell creating diffrently shaped red blood cells looking like a sickle

Huntingtons disease

• insertion

• recognised after 40

• dibilitating nerve damage - cant walk, speak and the dies

• caused by a insertion on gene HTT on chromosome 4

• CAG insertion rpeated multiple times => trinucloetide repeat expansion the more CAG the worse the symptoms

Frameshift mutation

caused by insertion or deletion that is not a multiple of three causing the whole genetic sequence to move often leading to non sense

deletion example

• CCR5 gene that make a protein CD4 which forms receptors on leukocytes to find pathogens

• It’s also an entry point for HIV

• delta 32 mutation - removal of 32 bases causes frameshift premature stop codon which leads to no production of the proetin and no entry

• beneifcial because stops HIV but person more suseptibel to West Nile virus

Causes of mutations

• mutagens: chemicals: enzymes in body or chemicals such as benzene

• radiation → nuclear plants

• Errors in DNA replication: sometimes DNA polymerase I can omit something

Where are mutations more common

CpG hotspots

where guanine follows cytosine

Can organisms invent a mutation

No

Germ cell mutation

passed on to future generation

Somatic cell mutation

• not passed on to future generation

• Often associated with cancer and tumors

Gene knochout

• making a gene unusable to see its effects

• library of knockout organimss used to compare

CRISPR-Cas9

1. Sequence targeted

2. gRNA created

3. gRNA and Ca9 enzyme mixed and injected into cell

4. gRNA guides Cas9 enzyme to the mutated DNA

5. PAM sequnece helps Cas9 attach

6. Cas9 removes the mutated fragemnt

7. can be left like that or fixed

Benefits of CRISPR

• more food

• treating harmful mutations like Huntingtons

• removing mutations that spread dengue or malaria in mosquitoes

Risks of CRISPR

• if germ cells passed on to future generations

• can impact other cells

• not avaialbel to everyone

Conserved sequences

similar across a group of species

Highly conserved sequences

idential or very very littel variation over long periods of evolution

→ code for necesarry things for survival eg tRNA