Genetics: Predisposition to Adult Onset Disease Flashcards
Why are adults referred to genetics?
- Diagnosis
- Predictive testing
- Carrier testing or cascade screening
- Family history (including cancer)
- Foetal loss or recurrent miscarriages.
What are the mechanisms of adult onset genetic disease?
- Single gene
- Chromosomal
- Mitochondrial
- Multifactorial
What is penetrance?
When the person has the abnormality in their gene, what si the risk they get the associated disorder
What conditions make risk estimation easier?
Single gene disorders with high penetrances
What is the impact of multifactorial conditions?
- There is a polygenic genetic component interacting with environmental factors
- Risk estimation is more difficult
- Risk alleles being identified for common/multifactorial disease
- Predictive value of each is very small
What are the principles of ethics in medicine?
- Respect for autonomy
- Beneficence
- Non-maleficence
- Justice
What are the rules regarding predictive tests?
- Test information must be usable for prevention or treatment
- Susceptibility testing requires adequate information about uncertainty
- Predictive testing requires proper counselling
- Children or adolescents should only be tested if there are potential medical benefits
- Third parties (employers, insurers) should have no access
What is the implication of shared genetic heritage?
- Genetic disease affects families, not individuals
- Discovery of a genetic disorder implies a risk for relatives
What are the general features of amyotrophic lateral sclerosis (MND)?
- Generally sporadic (1-2/100,000)
- Mean age onset 55yrs (younger in familial forms)
- 5-10% familial (AD +AR)
What are the clinical features of ALS?
- Progressive muscle weakness, wasting and increased reflexes (UMN +LMN signs)
- Limb and bulbar muscles involved
- Pure motor signs (with fasciculations)
- Cognition is spared
- Death due to respiratory failure
What gene is involved in ALS?
Cu/ZN superoxide dismutase (SOD gene)
What is the primary function of the SOD?
- Catalyses conversion of intracellular superoxide radicals produced during normal metabolism
- It is an ubiquitous enzyme which is expressed highly in motor neurones
What are the 3 forms of SOD present in humans?
SOD1
- Located in the cytoplasm
- Contain copper and zinc
- Chromosome 21
SOD2
- Located in the mitochondria
- Manganese in its reactive core
- Chromosome 6
SOD3
- Extracellular
- Contain copper and zinc
- Chromosome 4
What does the presence of SOD protect?
- Many types of cells from free radical damage that is important in ageing and ischaemic tissue damage
- SOD also helps protect cells from DNA damage, lipid peroxidation, ionising radiation damage, protein denaturation and other forms of progressive cell degradation
What is the penetrance of ALS?
Incomplete penetrance
