Mutations 2007-2008

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?

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

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

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?

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)

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

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

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.

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

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

What’s the value of mutations? 2007-2008