1. Mutations

2. When do mutations affect the next generation?
Point mutations
single base change
base-pair substitution
silent mutation
no amino acid change
redundancy in code
missense
change amino acid
nonsense
change to stop codon
When do mutations affect the next generation?

3. Point mutation leads to Sickle cell anemia
What kind of mutation?
Missense!

4. hydrophilic amino acid hydrophobic amino acid
Sickle cell anemia
Primarily Africans
recessive inheritance pattern
strikes 1 out of 400 African Americans
hydrophilic amino acid
hydrophobic amino acid

5. Mutations Frameshift shift in the reading frame insertions deletions
changes everything “downstream”
insertions
adding base(s)
deletions
losing base(s)
Where would this mutation cause the most change: beginning or end of gene?

6. How do mutations relate to dominant/recessive genes?
A mutation often causes a gene to be “broken”
Doesn’t make the protein the cell needs
Dominance/recessivness depends really on how much of the protein coded for by the gene is needed to express the trait properly
½ dose (1 gene copy)
Whole dose (2 gene copies)

7. Consider an autosomal recessive mutation like albinism…
Consider albinism
A = normal pigment
a = albino (no pigment) AA
individual has two normal genes and appears normal Aa
individual has one normal gene and one broken gene
But, evidently, one working pigment gene produces enough protein (pigment) for the body because Aa individuals appear normal aa
Individual has two copies of the broken gene
No pigment is produced
Individual appears as albino

8. But what about a dominant mutation like dwarfism?
Achondroplasia = dwarfism
In this case, having only one copy of the “normal height” gene is not enough to make you have normal height. You must have two copies. Why?
Evidently one copy of the gene will not be able to make enough of the protein (growth factor) needed to enable someone to attain normal height.
Only two copies of the “normal height gene” are enough to produce enough protein (growth factor)
Thus a = normal height; you have to have aa to have enough protein growth factor to attain normal height
aa = normal height
Aa = ½ the needed amount of growth factor produced = dwarf
AA = NO growth factor produced = individual dies

9. Cystic fibrosis Primarily whites of European descent
strikes 1 in 2500 births
1 in 25 whites is a carrier (Aa)
normal allele codes for a membrane protein that transports Cl- across cell membrane
defective or absent channels limit transport of Cl- (& H2O) across cell membrane
thicker & stickier mucus coats around cells
mucus build-up in the pancreas, lungs, digestive tract & causes bacterial infections
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.

10. bacteria & mucus build up mucus secreting glands
Chloride channel
transports chloride through protein channel out of cell
Osmotic effects: H2O follows Cl-
Effect on Lungs
normal lungs
airway
Cl-
Cl- channel
H2O
cells lining lungs
cystic fibrosis
Cl-
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
bacteria & mucus build up
thickened mucus hard to secrete
mucus secreting glands

11. Deletion leads to Cystic fibrosis
delta F508
loss of one amino acid

12. What’s the value of mutations?