5 - Genetic Variations & Modern Therapeutics

Define polymorphism

a discontinuous genetic variation divides the individuals of a population into two or more sharply distinct forms

• e.g. human blood groups

What genetic disorder can cause severe adverse drug reactions or make people non-responders?

polymorphisms in drug metabolism, drug transport, receptor sensitivity

What are consequences of mutation?

• cell death or enhanced cell proliferation (cancer)

• premature aging

• altered drug metabolism

• miscarriage

Define beneficial mutation

contributes to genetic variation within species, e.g. generation of antibiotic-resistant strains of bacteria

What are the 2 types of mutation?

1. somatic mutation (not inheritable)

2. germline mutation (heritable)

Define point mutation

• a single nucleotide is involved

• can be substituted, deleted, duplicated, inserted

• not observed under microscope

Define substitution

a single nucleotide is replaced by other

• silent

• nonsense

• missense

Define silent mutation

no change in amino acid sequence

Define nonsense mutation

no protein is formed

Define missense mutation

formation of new amino acid sequence

Define frameshift mutation

insertion, duplication, or deletion of a single nucleotide alters amino acid sequence that follows the point of the mutation

Define large mutation

structural chromosomal aberrations, observed under microscope

Define structural abnormality of chromosome

damage to a chromosome segment causing loss of structural integrity

What causes structural chromosomal abnormality?

formation of DNA breaks due to toxic chemicals, radiation

What are the types of structural chromosomal abnormality?

1. deletion

2. duplication

3. inversion

4. translocation

Define the types of deletion

1. terminal: requires a single break

2. intersitial: requires two breaks

Define the types of duplication

1. tandem: duplicated sections are adjacent to the original

2. displaced: the original and duplicated regions are separated by non-duplicated regions

Define inter-chromosomal translocation

exchange of chromosome segments between two non-homologous chromosomes

Define very large mutation

numberical chromosomal aberrations; observed under microscope

Define gene therapy

novel therapeutic branch of modern medicine for correcting a defective disease-causing gene

What are the cell types of gene therapy?

1. somatic (noninherited)

2. germline (inherited)

Define gene replacement therapy

replacement of a homozygous mutant gene

Define gene augmentation therapy

correction of a heterozygous mutant gene

Define gene inhibition therapy

a blocking gene is introduced to eliminate the activity of a gene that promotes the growth of disease-related cells

How is gene therapy achieved?

1. introduction of “suicide” gene

2. introduction of “marker” gene

Define suicide gene therapy

introducing viral or bacterial genes to tumor cells, allowing conversion of a non-toxic compound to a lethal medication

Define marker gene therapy

expression of a protein that marks the cells so that the diseased cells are attacked by the body’s natural immune system

How is targeted gene therapy used to treat cancer?

a new receptor (CAR) is added to a patient’s T cells, forming a CAR-T cell

Define in vivo gene elivery

direct delivery of a therapeutic gene into the cells of a particular organ in the body via viral or non-viral vector

Define ex vivo gene delivery

transfer of a therapeutic gene into cultured cells and then introduction of genetically modified cells into the body

What are the challenges of gene therapy?

• delivering the therapeutic gene to the right place & switching it

• can induce immune response

• risk of disrupting activity of a normal gene

• cost

Define precision/personalized medicine

the customization of medical treatment based on a patient’s genetic makeup and other individual characteristics to optimize drug efficacy and minimize adverse effects