1. Lesson Objectives 2/20/15
Content Objective: Recognize how protein structure affects function.
Language Objective: Explain the significance of the STOP codon.

2. Entry Task: Educated Guess!
Given your understanding of Central Dogma, hypothesize what the purpose of a “stop” codon might be. Write your hypothesis in your lab notebook, and bonus points for a picture!

3. Cystic Fibrosis

4. Cystic Fibrosis
Affects 30,000 Americans and about 70,000 people worldwide.
In people with CF, a defective gene and its protein product cause the body to produce unusually thick, sticky mucus that:
Clogs the lungs and leads to life-threatening lung infections.
Obstructs the pancreas and stops natural enzymes from helping the body break down food and absorb vital nutrients.

5. Cystic Fibrosis Pathology

6. Cystic Fibrosis
In the 1950s, few children with CF lived to attend elementary school. Since then, tremendous progress in understanding and treating CF has led to dramatic improvements in the length and quality of life for those with CF. Many people with the disease can now expect to live into their 30s, 40s and beyond.
Source: Cystic Fibrosis Foundation website

7. Cystic Fibrosis Genetics
CF is caused by mutations in a gene that produces a protein, called CFTR. The CFTR protein controls the flow of salt and water in and out of the cells of organs like the lungs and pancreas.
To have cystic fibrosis, a person must inherit two copies of the defective CF gene — one copy from each parent. Both parents must have at least one copy of the defective gene.

8. The Cystic Fibrosis Transmembrane Conductance Receptor (CFTR) conducts chloride ions across epithelial cell membranes.

9. CFTR Mutations

10. Types of Genetic Mutations

11. There Are 3 “Stop” Codons

12. STOP! The Game Start with 5 randomly selected amino acids (AAs)
Identify an RNA sequence encoding the AAs
Convert the RNA sequence to DNA
Mutate a single DNA base to introduce nonsense mutation (a STOP codon)
If no STOP is found, add additional AAs
The first person to STOP the growing DNA sequence wins

13. H C I V V

14. H C I V V
His – Cys – Ile – Val – Val

15. H C I V V
His – Cys – Ile – Val – Val CAU – UGU – AUU – GUA – GUA CAU – UGA – AUU – GUA – GUA

16. A K A V Y

17. A K A V Y
Ala – Lys – Ala – Val – Tyr

18. A K A V Y
Ala – Lys – Ala – Val – Tyr GCU – AAA – GCU – GUU – UAU GCU – AAA – GCU – GUU – UAA

19. F K Q P F

20. F K Q P F
Phe – Lys – Gln – Pro – Phe

21. F K Q P F
Phe – Lys – Gln – Pro – Phe UUU – AAG – CAA – CCC – UUC UUU – UAG – CAA – CCC – UUC

22. L Y W H G

23. L Y W H G
Lys – Tyr – Trp – His – Gly

24. L Y W H G
Lys – Tyr – Trp – His – Gly CUA – UAU – UGG – CAU – GGA CUA – UAA – UGG – CAU – GGA