Genetic Diseases and Genetic Counselling

1. A B D Z ? C X Y Cl- Cl- Cl- Cl- Cl- Cl- Genetic Diseases and Genetic Counselling GHB 2005

2. Every gene carries information telling the body how to make a particular protein Adult cells have two copies of each gene, so… …if one copy of the gene doesn’t work, the cell has a ‘backup’

3. New versions of genes can be produced by … …mutation. These new versions or… alleles... …can produce proteins that either: - do not work, or - do something which they are not supposed to do These defective genes can cause serious … …genetic diseases

4. Cl- Cl- Cl- CF membrane proteins Cell membrane Cl- The CF protein pumps chloride ions from one side of the membrane to the other Example: Cystic fibrosis The cell membranes of the cells lining the lungs and air passages contain CF membrane proteins

5. H2O Cl- Cl- Cl- Cl- Cl- H2O H2O H2O Cl- Cell membrane H2O Cl- H2O Water molecules follow the chloride ions across the semi-permeable cell membranes by… The CF protein produces a higher concentration of chloride ions on one side of the membrane than the other …osmosis.

6. The body uses the CF chloride pump to move water into secretions like the mucus found in the trachea and sweat. If your cells cannot make working chloride pumps, your mucus becomes too thick and sticky due to lack of water However, to make a functioning chloride pump, each cell only needs one good copy of the gene for it. recessive So, cystic fibrosis is

7. C c Healthy gene produces working chloride pump Defective gene produces non-working chloride pump Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- This individual does not suffer from cystic fibrosis, but is a carrier

8. Neither copy of the gene carried by this individual can produce a working chloride pump c c Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- This individual will suffer from cystic fibrosis REMEMBER: Genes do NOT exist to cause disease… … defective genes cause disease

9. Gene Structural region (code for protein) Operator region Length of DNA Repressor binding site RNA polymerase binding site How are genes switched on and off? Cells only use some of their genes most of the time You do not want nerve cells making liver cell proteins Most genes can be switched on or off Example

10. The enzyme RNA polymerase attaches itself to its binding site… … and moves down the strand of DNA decoding the gene RNA polymerase Repressor protein attaches itself to its binding site… RNA polymerase is blocked and cannot attach to DNA Repressor protein ON OFF

11. If the repressor binding site is lost… … the repressor protein cannot bind to the DNA There is nothing to stop DNA polymerase binding… Having a healthy copy of this gene will not switch the defective copy off, so… … so the gene is permanently ON … the disease caused by the defective allele is… … dominant

12. Genetic Counselling A genetic counsellor advises couples on the likelihood of their children having a particular genetic disease. The genetic counsellor considers: - how common the gene is in the general population e.g. 1 in 17 people in the UK are carriers for cystic fibrosis - the two family trees of the couple i.e. can they work out the genotype of the couple? - the results of genetic tests

13. Looking at Family Trees Unaffected male Affected male Unaffected female Affected female Sex not known Carriers - unaffected heterozygotes Male of unknown genotype/phenotype ?

14. mating Dead consanguineous mating (Kept it in the family) Parents with son and daughter Parents with son and twin daughters Oldest to youngest shown left to right Identical twins

15. The pedigree below shows a family with a history of a rare genetic disease Is the disease recessive or dominant? Explain you answer ? ? ? ? ? ? ? • The disease is recessive: • It skips generations • Carriers have the gene but are not affected

16. Assume that A, B, C and D do not suffer from the disease – what is their genotype? Explain your answer. ? ? A B ? ? ? C ? ? D • All four are heterozygous carriers. • C&D must be carriers to produce offspring with the disease • D must have inherited the gene from B, and C from A.

17. B A ? ? ? C D What are genotypes and phenotypes of X and Y? X Y • Both are heterozygous carriers. • they must inherit a copy of the disease allele from their father • they must inherit the healthy allele from their mother

18. B A ? Z C D X Y What are the chances of Z being a carrier? 1:2 or 50%: - He must inherit the healthy allele from his father - He has a 50% chance of inheriting the disease gene from his carrier mother

19. A B D Z ? C X Y Z is concerned that any children that he may have will suffer from the disease. What advice would you give him? 1. If possible, get himself tested to see if he is a carrier - If he is not a carrier, the probability of his children being sufferers is 0 2. Try to marry outside the family - An unrelated person is less likely to be a carrier

20. The pedigree below shows another family with a history of a genetic disease Is the disease dominant or recessive? Explain your answer A ? ? B X ? Y ? ? C K L D E F • This disease is dominant: • It is passed from A to E & F without skipping a generation • (there are no carriers) • It can be inherited from only one parent

21. What is K’s phenotype and genotype? Explain your answer A ? ? B X ? Y ? ? C K L D E F K is unaffected (homozygous recessive) K must have same genotype and phenotype as twin, L

22. What are X and Y’s phenotype and genotype? Explain your answer A ? ? B X ? Y ? ? C K L Z D E F X and Y are both affected (heterozygous) - Both must have carried gene for Z to have inherited it - Both will have inherited the normal alleles from their mothers

23. E is concerned that any children she has will be affected. What would you advise her? A ? ? B X ? Y ? ? C K L Z D E F Probability of any child being affected is1:2 or 50%: - they must inherit the healthy allele from F - they have a 50% chance of inheriting the disease gene from E