Risk of transmission of genetic disease Flashcards
State the differences between monogenic and complex diseases.
Monogenic diseases are rare, have a clear inheritance pattern and are not affected by environmental factors Complex diseases are the opposite
State the difference between mutations and polymorphisms.
Mutations are any changes in genetic material that are hereditary Polymorphisms are mutations which occur at >1% frequency in the population
When are polymorphism called a mutation
When they cause a disease. Polymorphisms may contribute to complex disease.
State two different types of point mutations
Non-sense: codon changes to code for a stop codon so the polypeptide chain ends prematurely.
Mis-sense: Mutation means that the codon codes for a different amino acid
State two types of frame shift mutations.
InDel
either deletion or insertion
Give an example of an autosomal dominant disease and the mechanism of action.
Huntington’s Disease – mutations in the HTT gene on Chr 4, which codes for huntingtin. Mutation leads to production of a toxic protein that accumulates and forms clumps in organs. Causes cell death in the basal ganglia in the brain. It is caused by an unstable CAG repeat – the more repeats you have the more likely you are to get HD. Severity increases with time and age of onset decreases.
What does Huntington cause?
Motor, cognitive and psychiatric dysfunction- hyperkinesia.
Give features of autosomal dominant
- at least one affected parents
- 50% risk of child being affected
Give features of autosomal recessive
- No affected parent
- usually no family history
- 25% risk of child being affected
- 50% chance of child being carrier
Give an example of an autosomal recessive disease and the mechanism of action and what is the most common one?
Cystic Fibrosis – caused by a mutation in the CFTR gene on Chr 7, which affects chloride ion function in epithelial cells. This disrupts of salt/water regulation causes thick mucus and leads to symptoms.
Most common- delta F508
What does Cystic fibrosis cause?
- Thick mucus in lungs causing breathing difficulties and infection.
- Blockages in pancreas affecting digestive enzymes -
Give an example of a mutation and is symptoms in the same gene causing two different conditions
Congenital absence of the vas deferens – caused by mutations in CFTR
- vasa deferentia fail to form properly
- causes infertility
- affects men 1:2500
Give features of X-Linked recessive
- No affected parents
- usually only males affected
- transmitted by female carrier
- sons have a 50% risk of being affected
- daughters have a 50% chance of being a carrier
Give an example of a X-linked recessive condition. Symptoms?
Haemophilia A and B – A is caused by a mutation in the F8 gene on Chr X which encodes factor VIII. B – caused by mutation in F9 gene which encodes factor IX
same disease, different genes mutated.
A blood-clotting disorder
Affected people bruise easily and bleed for longer
What are the general molecular mechanisms of the different types of genetic disease (autosomal dominant, autosomal recessive, co-dominant)?
Dominant – toxic product produced (treatment aims to neutralise toxic product or switch off the mutated gene), effects of the mutated gene ‘mask’ normal copy
Recessive – absence of functional protein (treatment aims to regain function by replacing the gene or protein product)
Co-dominant: effects of both mutated and normal genes apparent in people with both e.g. sickle cell trait
*treatment same as dominant
