Topic 5 - D1.3 - Mutations & Gene Editing SL/HL

Mutations

Any change to the DNA or RNA base sequence of a cell or virus. These can occur randomely at any location within the genome.

Gene Mutations

Changes in the nucleotide sequence of a gene

Single-nucleotide polymorphisms (SNP’s)

Occur when a single nucleotide in a gene is changed; results in a different amino acid in a protein. —> These are the result of single-nucleotide base substitutions.

Sickle cell anemia is an example of this; caused by a single base substituion in a gene required for making hemoglobin.

Allele

An alternative version of a gene; this is produced by a mutation which created a single-nucleotide polymorphism.

Polymorphism

Refers to the occurence of 2 different phenotypes within a population.

Base Substitution Mutations

Type of mutation: changes the nucleotide sequence for one codon within a gene. —> this may not change the amino acid sequence due to the degeneracy of the genetic code. (No frameshift of the gene)

Insertion Mutations

Type of mutation: adds one (or more) nucleotides to a gene. Changes many codons; Frameshift occurs: may produce a protein with many different amino acids.

Deletion Mutation

Type of mutation: removes one (or more) nucleotides from a gene. Changes many codons; frameshift occurs. Will produce a protein with many different amino acids.

Frameshift Mutations

“Group” of mutations: result from insertion or deletions of nucleotides (which are not in multiples of 3) and change/shift all codons after the mutation.

Polypeptides produced by this “group” of mutations are unlikely to function, because many codon changes produce different shapes of amino acids, thus impairing it’s function.

Point Mutations

“Group of mutations”: change one nucleotide in a single codon; may change a single amino acid in a protein.

Mutagens

Causes of gene mutations; agents that cause permanent, heritable changes to the DNA of cells. Ex. Radiation, alpha-particles, beta-particles, tobacco smoke, alkylating agents used in chemotherapy.

Consequences of Mutations

Mutations can be neutral, beneficial, or harmful.

Most mutations are neutral due to the degeneracy of the genetic code, or because they occur within non-coding sections of DNA.

Some mutations are beneficial for the survival and reproduction of the organism

Germ Cells

Type of cells that develop into gametes; sperm or eggs. —> Allele of a mutated gene in a gamete/this type of cell will be present in the zygote after fertilisation.

Somatic Cells

Type of cells: any cells that aren’t reproductive cells. Mutations in this type of cell aren’t passed onto offspring.

Cancer

Uncontrolled cell division. Mutations to proto-oncogens in somatic cells can result in this disease.

Natural Selection

The differential survival due to the inheritance of traits that make an individual more likely to survive and reproduce. —> This causes the evolution of species over time.

Evolution

Caused by natural selection, and genetic variation.

Genetic Variation

Needed for evolution by natural selection. Mutations are the main source of this term.

Commercial Genetic Tests

Type of test; more widely available to understand a person’s genome, potential health and disease risk. Without expert interpretation, this information could be problematic.

Gene Knockout

Technique where a targeted gene is inactivated or removed from an organism. This technique allows scientists to study the impact of an organism by removing a gene.

Gene Knockout libraries created for:

Mice, fruit flies, zebrafish.

CRISPR-Cas9

Technology; allows scientists to modify or delete specific sections of DNA, such as genes.

CRISPR Technology Mechanism - Step 1/3

CRISPR guides the enzyme Cas9 to cut DNA At a specific location.

CRISPR Technology Mechanism - Step 2/3

A guide RNA (gRNA) molecule is used to target a specific sequence in a gene. gRNA has a sequence of complementary bases to the target sequence.

CRISPR Technology Mechanism - Step 3/3

Enzyme Cas9 cuts the gene at the target location; this can knockout the gene, or a DNA sequence can be inserted into the DNA where the gene was cut.

Uses of CRISPR-Cas9

• Gene therapy: technology can be used to replace or repair a gene responsible for genetic diseases.

• Genetic research: technology is an effective method to knockout genes, allowing researchers to better understand the action of specific genes.

• Malaria prevention: technology can be used to modify the genomes of mosquitoes, which could reduce the spread of malaria.

Sickle Cell Anemia Cause

Disease; caused by a single-base substitution mutation.

Curing Sickle Cell Anemia

CRISPR-Cas9 can be used to repair the hemoglobin gene for blood stem cells removed from a patient with this disease. The stem cells can then be re-inserted into the patient to cure them.

Ethical Issues of CRISPR

International efforts to harmonize regulation of the application of genome editing technology, such as CRISPR.

Conserved Gene Sequences

Identical or similar genes across a species or group of species.

Highly Conserved Sequences

Identical or similar genes over long periods of evolution.

Functional Constraint Hypothesis

1 hypothesis to explain the conservation of gene sequences: suggests that gene sequences are essential to the structure and function of the protein coded by the gene. Any mutation to the gene sequence is naturally selected against as the associated protein would not function.

Slower Rates of Mutation Hypothesis

Another hypothesis to explain the conservation of gene sequences: suggests that highly conserved sequences are under selective pressure to maintain their function, which results in a slower rate of mutation in these sequences.