Presentation on theme: "Huntington Disease An overview"— Presentation transcript:
1 Huntington Disease An overview This PowerPoint file contains a number of slides that may be useful for teaching of genetics concepts.You may use these slides and their contents for non-commercial educational purposes.
2 Huntington Disease (HD) This presentation includes:Clinical classification and features.Structure and molecular basis of the HD gene.Clinical photographs showing involuntary movements in HD, and brain tissue of normal and affected patients.Pedigree of an HD family.Probability of inheriting the HD gene change.Advantages and disadvantages of predictive testing for HD.
3 Huntington Disease (HD) Clinical ClassificationMovement/Cognitive/Psychiatric disorderMean onset age years.PrevalenceIncidence >1 in 10,000.Genetic TestingDiagnosticPresymptomatic – counselling protocol.
6 Huntington disease - a triplet repeat disease CAG CAG CAG CAG CAG CAG CAG CAG CAG CAG CAG …... CAG11-34 CAG triplet repeats are normal:encodes a run of glutamine amino acid residues in the protein.A run of > 34 glutamine residues causes the protein to aggregate in the brain cells andcause progressive cell death.Runs of >34 CAG repeats in the HD gene expand further (particularly during male meiosis) causing earlier age of onset in children of men who have the gene – anticipation.
10 Observations show that 40% of people with the HD gene are asymptomatic at the age of 50 Intuition says probability of parent having gene at age 50 = 1/2 x 1/2.5 = 1/5.Therefore son’s risk is ½ x 1/5 = 1/10.BUT THIS IS INCORRECT! Probabilities should be multiplied only when they are completely independent of each other, and these are not. Developing HD is conditional on having inherited the gene.Have to use Bayes theorem:-His mother’s probability of having gene for HD and asymptomatic at age 50 is 1/3.5 His risk is therefore 1/7.Probability: ½ at birthProbability of inheriting the altered HD gene at birth: ½ x ½ = ¼
11 Advantages of predictive testing for Huntington disease Uncertainty of gene status removed.If negative:concerns about self and offspring reduced.If positive:make plans for the futurearrange surveillance/treatment if anyinform children/decide whether to have children.
12 Disadvantages of predictive testing for Huntington disease If positive:removes hopeintroduces uncertainty (if and when)known risk to offspringimpact on self/partner/family/friendspotential problems with insurance/mortgage.If negative:expectations of a ‘good’ result‘survivor’ guilt.