1. Genetic Screening

2. Objectives Be able to describe the processes involved in genetic screening through DNA hybridisation. Be able to describe the role of a genetic counsellor, recalling knowledge of genetic crosses. Be able to consider the views of people who may have their DNA screened.

3. Genetic Screening Genetic screening can be used to find out whether a person is carrying a specific genetic mutation (altered gene) that causes a particular medical condition. What disorders might we screen for? – Cystic fibrosis – Presence of oncogenes – Alzheimer’s disease – Sickle cell anaemia

4. How does it work? 1. DNA taken from a patient is purified and amplified (copied). What is the name of the in vitro process that copies DNA? How does the polymerase chain reaction work? Why do you think the PCR is used in genetic screening?

5. How does it work? 2. Amplified DNA is digested. Which enzymes are used to digest DNA? How do restriction endonucleases work? (HINT: restriction site, blunt ends, sticky ends)

6. How does it work? 3. Restriction fragments are separated according to size. What is the name of the process that separates DNA fragments by size? How does gel electrophoresis work?

7. How does it work? 4. Separated DNA fragments are bound to a nylon membrane and treated so they become single-stranded. What is the name of this process? How does Southern blotting work?

8. How does it work? 5. A DNA probe with a sequence complementary to that of a section of the target gene is added. The probe is radioactively or fluorescently labelled. What is the name of this process? How does DNA hybridisation allow us to screen a DNA sample for a harmful allele of a gene?

9. Let’s have a try! Split yourselves into 4 groups and collect the following nucleotides: A – 7 Follow the instructions you are T – 7 given to build a piece of DNA. G – 8 C – 8 Bring it to the front when you’ve finished.

10. Sickle Cell Anaemia A mutation in the haemoglobin gene leads to sickle-shaped red blood cells. The mutated haemoglobin allele (Hb S ) is codominant with the allele for normal haemoglobin (Hb A ). Hb A Hb A = Healthy Hb A Hb S = Sickle cell trait Hb S Hb S = Sickle cell sufferer

11. We’re going to look at different combinations of alleles: What steps would scientists have taken to get to this point? The probe has the sequence CGTGGA. With what DNA sequence will it hybridise?

12. After PCR, restriction enzymes and gel electrophoresis… DNA is treated to break the hydrogen bonds and the probe is added. Potential outcomes: Person 1 Person 2 Person 3

13. What does it mean? The presence of a band tells us the probe has hybridised with the DNA, so the mutation is present. Wider bands tell us more probe molecules have bound to the DNA – what does this mean?

14. This is not the only method for genetic screening. Other methods include: DNA sequencing (later this week!) FISH (fluorescence in situ hybridisation - fluorescent labelling of DNA in cells) MLPA (detects large deletions and duplications in DNA) My sister and her husband – their job is genetic screening!

15. Uses of Genetic Screening For whom might we want to provide genetic screening?

16. Uses -Screening of newborns (e.g. sickle cell anaemia) -Screening for disorders that affect people later in life (e.g. Alzheimer’s) -Screening for different oncogenes to select the most appropriate treatment for cancer -Screening of adults for increased risk of disease (e.g. breast cancer) -Screening of potential parents to assess likelihood of passing on harmful alleles (e.g. cystic fibrosis).

17. James Watson (of ‘Watson and Crick’ fame) Had his genome sequenced to test a new method (in 2008) – it has been published online. All information about a gene which massively increases the likelihood of him developing Alzheimer’s has been removed – he didn’t want to know.

18. Genetic Counselling Clinical genetics involves counselling people who have DNA screening. Includes information about disorders, probability of passing on disorders to children, issues with the disorder etc.. Discuss the scenarios with your group. What would you tell the patient in each case? If you were the person being screened, would you want to know the results? Explain your reasons!

19. Objectives Be able to describe the processes involved in genetic screening through DNA hybridisation. Be able to describe the role of a genetic counsellor, recalling knowledge of genetic crosses. Be able to consider the views of people who may have their DNA screened.

20. Something to think about… If you could have your DNA screened for alleles linked with diseases, would you? What if you had to share the information with others, e.g. insurers, employers etc.?

21. Homework Exam questions – hand in by Tuesday please!