Screening for clinically important genes

1. Screening for clinically important genes Tuesday 27th March

2. Genetic Screening • This can be on newborns (neonatal)… • or on unborn babies (amniocentesis, CVS) • Or on adults

3. Genetic screening • Many genetic disorders are the result of gene mutations e.g. deletions or substitutions. • The mutation may result in a dominant allele (e.g. Huntington’s) or a recessive allele (e.g.CF), in which case heterozygous individuals are carriers. • There is usually a family history with genetic diseases, especially for dominant mutations. • It is important to screen individuals who may carry a mutant allele • Genetic counsellors can offer advice to potential parents, who think they may be carriers • Would you want to know?

4. How genetic screening happens… • Hundreds of different DNA probes are fitted in an array (pattern) on a glass slide. • The donor’s DNA (i.e. the donor is the person wishing to know if they have a mutant allele or not)… • …is first made single stranded…(how?) • …and is then added to the array. • The donor DNA will bind to any probes which are complimentary to its base sequence. • What is an advantage of this technique? • You can screen for many different genetic disorders simultaneously • See Nelson Thornes p272

5. Oncogenes“oncology” is the study of cancer • Cause cancer • Can be screened for • Tumour suppressor genes inhibit cell division • Some cancers are caused by a mutation which prevents a tumour suppressor gene from suppressing tumours. • Mutations of both alleles are needed to inactivate the suppressor genes and so initiate the development of a tumour • People with one mutated tumour suppressor gene are at greater risk of cancer • So, what is an oncogene? • A mutated version of a proto-oncogene

6. Mutagens / early diagnosis & treatment • Genetic Screening can tell individuals how at risk of cancer they are. In the light of this knowledge, they can then… • make informed decisions about whether to avoid mutagens or not (e.g. carry on / give up smoking) • Check themselves more regularly for the early signs of cancer e.g. breast lumps  earlier diagnosis  better chance of successful treatment (e.g. gene therapy for liver cancer) • What might the gene therapy involve? • Addition of a supplementary tumour suppressor gene

7. Genetic Counselling • Aim = to allow individuals to make informed decisions about themselves or their offspring • e.g. a man and a woman want to start a family. They both have relatives with CF, they don’t have CF. • Would you advise a screening test? • Assume they are screened for the mutant CFTR allele and both are found to be carriers. What are their chances of their having a child with CF? • As the allele is recessive, 1 in 4, 25%, 0.25

8. Carriers of CF • Two carriers have a 1 in 4 chance of having a child with CF. What are their options…? • Natural pregnancy, amniocentesis, possible termination (BUT treatment of CF is improving, there’s the possibility of gene therapy, termination is becoming less necessary; some religions would not allow termination anyway) • Pre-implantation Genetic Diagnosis / Screening (PGD / PGS) • Don’t have children • Adopt • Natural pregnancy, don’t have amniocentesis, possibly have child with CF • Is it cruel to risk having a child with CF? Think: Debilitating lung & digestive symptoms; unpleasant / inconvenient treatment; poor quality of life; possible early death

9. Genetic Counsellors…have a role before or after conception • Advise whether to screen for mutant alleles (in parents, in fetus) • If parents are screened, explain the probabilities for each genotype / phenotype in the offspring • Explain further tests which could give a more accurate prediction of the outcome of a pregnancy which has already begun • They also give advice on which consequences of having a child with a genetic disease? • Emotional (upsetting for both parent and child) • Psychological (being “different” may affect behaviour) • Medical (possible lifelong pain, treatment) • Social (will they ever “fit in” with peers, gain friends) • Economic (healthcare costs, will they ever work?)

10. Cancer screening… • Genetic counselling is closely linked to genetic screening, the results of which form the basis for an informed discussion. Screening can detect… • Oncogene mutations. These can predict the kind of cancer and which treatment to give • Other gene changes (in addition to the cancer) that predict if a patient will benefit from a particular treatment. E.g not all women with breast cancer will benefit from the use of Herceptin. • A reappearance of cancer cells indicating a relapse e.g this can happen with patients with leukemia, who are in remission

11. I advise you to… • Look at the “synoptic exercise” on sickle-cell anaemia in Nelson Thornes p273… • This will prepare you “The Essay”

12. Implications of Genetic Screening • With information comes power, opportunity and responsibility… • Who decides who should be screened? It’s expensive and budgets are limited • Who has access to the test results? Employers? Insurers? Lenders? • Does a carrier have a responsibility for the alleles they pass on? Note – the genetic disease Tay-Sachs involves constant pain and death at the age of four years • Does mankind have a responsibility to maintain genetic diversity? Should we preserve mutant genes for the sake of human evolution? • Who decides what is a defect? Tay-sachs, yes, but ginger hair…?

13. Questions • Give two reasons in favour of carrying out genetic screening, and two reasons against doing so. • Outline the process of genetic screening • Genetic screening shows that a person has one mutant allele of the tumour suppressor gene • What is the role of the tumour suppressor gene? • How might the person use the information from the genetic screening test?