1. Mutations Changes to DNA

2. Mutations Changes to DNA are called mutations change the DNA
changes the mRNA
may change protein
may change trait
DNA
TACGCACATTTACGTACG
mRNA
AUGCGUGUAAAUGCAUGC aa
protein
trait

3. Types of mutations Changes to the letters (A,C,T,G bases) in the DNA
point mutation
change to ONE letter (base) in the DNA
may cause change to protein, may not
frameshift mutation
addition of a new letter (base) in the DNA sequence
deletion of a letter (base) in the DNA
both of these shift the DNA so it changes how the codons are read
big changes to protein!

4. Point Mutations THEFATCATANDTHEREDRATRAN THEFATCARANDTHEREDRATRAN OR
One base change
can change the meaning of the whole protein
THEFATCATANDTHEREDRATRAN
THEFATCARANDTHEREDRATRAN OR
THEFATCATENDTHEREDRATRAN

5. Point Mutations AUGCGUGUAUACGCAUGCGAGUGA MetArgValTyrAlaCysGluStop
Missense mutation = changes amino acid
AUGCGUGUAUACGCAUGCGAGUGA
MetArgValTyrAlaCysGluStop
AUGCGUGUAUACGUAUGCGAGUGA
MetArgValTyrValCysGluStop

6. Sickle cell anemia Hemoglobin protein in red blood cells
strikes 1 out of 400 African Americans
limits activity, painful & may die young
Only 1 out of 146 amino acids

7. Sickle Cell Advantage
Malaria

8. Malaria kills 2-3 million each year

9. Point Mutations AUGCGUGUAUACGCAUGCGAGUGA MetArgValTyrAlaCysGluStop
Silent mutation = no change to protein
AUGCGUGUAUACGCAUGCGAGUGA
MetArgValTyrAlaCysGluStop
AUGCGUGUAUACGCUUGCGAGUGA
MetArgValTyrAlaCysGluStop

10. Point Mutations AUGCGUGUAUACGCAUGCGAGUGA MetArgValTyrAlaCysGluStop
Nonsense mutation = change to STOP
AUGCGUGUAUACGCAUGCGAGUGA
MetArgValTyrAlaCysGluStop
AUGCGUGUAUAAGCAUGCGAGUGA
MetArgValStop

11. Does this change the sentence?
Frameshift Mutations
Add or delete one or more bases
changes the meaning of the whole protein
THEFATCATANDTHEREDRATRAN
Does this change the sentence?
A LOT!
Delete one!
Add one!
THEFATCANTANDTHEREDRATRAN OR
THEFATCAANDTHEREDRATRAN

12. Frameshift Mutations AUGCGUGUAUACGCAUGCGAGUGA
Addition = add one or more bases
AUGCGUGUAUACGCAUGCGAGUGA
MetArgValTyrAlaCysGluStop
AUGCGUGUAUACGUCAUGCGAGUGA
MetArgValTyrValMetArgValA

13. Frameshift Mutations AUGCGUGUAUACGCAUGCGAGUGA
Deletion = lose one or more bases
AUGCGUGUAUACGCAUGCGAGUGA
MetArgValTyrAlaCysGluStop
AUGCGUGUAUACGAUGCGAGUGA
MetArgValTyrAspAlaSerGA

14. Cystic fibrosis Broken salt channel in cells
strikes 1 in 2500 white births
gene codes for a protein channel that allows salt to flow across cell membrane
broken protein doesn’t work as channel
doesn’t allow salt out of cell, so water doesn’t flow out either
thicker & stickier mucus coating around cells
mucus build-ups in lungs & causes bacterial infections
destroys lung function
without treatment children die before 5; with treatment can live past their late 20s
Cystic fibrosis is an inherited disease that is relatively common in the U.S. Cystic fibrosis affects multiple parts of the body including the pancreas, the sweat glands, and the lungs. When someone has cystic fibrosis, they often have lots of lung problems. The cause of their lung problems is directly related to basic problems with diffusion and osmosis in the large airways of the lungs.
People without cystic fibrosis have a small layer of salt water in the large airways of their lungs. This layer of salt water is under the mucus layer which lines the airways. The mucus layer in the airways helps to clear dust and other inhaled particles from the lungs.

15. mucus & bacteria build up = lung infections & damage
Salt channel
transports salt through protein channel out of cell
Osmosis problems!
Effect on Lungs
normal lungs
airway
salt
salt channel
normal mucus
H2O
cells lining lungs
cystic fibrosis
salt 
thick mucus
In people without cystic fibrosis, working cystic fibrosis proteins allow salt (chloride) to enter the air space and water follows by osmosis. The mucus layer is dilute and not very sticky.
In people with cystic fibrosis, non-working cystic fibrosis proteins mean no salt (chloride) enters the air space and water doesn't either. The mucus layer is concentrated and very sticky.
People with cystic fibrosis have lung problems because:
Proteins for diffusion of salt into the airways don't work. (less diffusion)
Less salt in the airways means less water in the airways. (less osmosis)
Less water in the airways means mucus layer is very sticky (viscous).
Sticky mucus cannot be easily moved to clear particles from the lungs.
Sticky mucus traps bacteria and causes more lung infections.
Therefore, because of less diffusion of salt and less osmosis of water, people with cystic fibrosis have too much sticky mucus in the airways of their lungs and get lots of lung infections. Thus, they are sick a lot.
H2O
mucus & bacteria build up = lung infections & damage

16. Deletion leads to Cystic fibrosis
Loss of one
amino acid!

17. Questions?