1. Ch. 16
Part 3: Mutations

2. Mutations Unpredictable change in the genetic material
Gene Mutation: change in structure of a DNA molecule that produces a different allele of a gene
Chromosomal mutation (ABERRATION): changes in the structure or number of chromosomes in an organism
Give rise to new alleles
Causes:
Random
Environmental factors (increase chances)
Ionizing radiation
UV Radiation
Chemicals
MUTAGEN!

3. Gene Mutations 3 Main types Point Mutation
Base Substitutions
May lead to silent mutation (mutation with no apparent affect on organism)
Frameshift Mutation (significant effect)
Base addition (insertion)
Base deletion (deletion)

4. Base Substitution Replacement of one base or nucleotide with another
Usually do not change amino acid
Sometimes causes a change in the protein made
Silent Mutation
When a substitution does not cause a change in the protein expressed by a gene
Remember some codons represent the same amino acid
Example: GAA and GAG both code for Glu

5. Point Mutation A point mutation is a simple change in one base of the gene sequence. This is equivalent to changing one letter in a sentence, such as this example, where we change the 'c' in cat to an 'h': Original: The fat cat ate the wee rat. Point Mutation: The fat hat ate the wee rat.

7. Insertion or Deletion Nucleotide is removed or added More disastrous
mRNA is read as triplet codes
Adding/removing bases changes these three letter codes
Codons downstream from insertion/deletion will be regrouped and probably code for a non-working protein
Result: FRAMESHIFT MUTATION
Shift the “reading” frame of the genetic message

8. Frameshift mutation Original: The fat cat ate the wee rat.
Frame Shift: The fat caa tet hew eer at.

10. Sickle Cell Anemia Sickle cell anemia
1/500 African Americans have the disorder
Co-dominant allele
Causes blockages in blood vessels, preventing oxygen from getting to other cells and tissues
Beneficial in central and east Africa because it helped destroy malaria
If you had SCA, your body would destroy the sickle cells to protect itself and in the process, destroy the malaria parasite as well

11. DNA and Sickle Cell Anemia
Review hemoglobin
2 alpha chains
2 beta chain
Sickle Cell Anemia
Inherited blood disorder
BASE SUBSTITUTION Mutation to DNA sequence that codes for beta chains
One DNA nucleotide is replaced with a different nucleotide
Normal amino acid sequence for beta chain:
VAL-HIS-LEU-THR-PRO-GLU-GLU-LYS-
HbA allele (normal hemoglobin allele)
DNA triplet code for Glu is CTT
Mutated amino acid sequence for beta chain:
VAL-HIS-LEU-THR-PRO-VAL-GLU-LYS-
HbS allele (sickle cell allele)
DNA triplet code for CTT is changed to CAT, which no longer codes for Glu, but instead Valine
HbA allele: allele for normal B-globin polypeptide
HbS allele: allele for normal B-globin polypeptide
HbAHbA : Normal
HbAHbS : Normal but carrier
HbSHbS: sickle cell anemia

12. Effects of Sickle Cell Mutation
Glutamic acid
Found on outside of hemoglobin
Hydrophilic aa
Interacts with water molecules, makes hemoglobin soluble (good!)
Valine
Hydrophobic aa
Does not interact with water, makes hemoglobin less soluble (BAD!)
When abnormal hemoglobin is in area of LOW oxygen concentration, they stick together because the outside is now hydrophobic
Abnormal hemoglobins form long chains of insoluble fibers
These pull the red blood cells that contain the abnormal hemoglobin inwards and out of shape (become sickle shaped instead of round)
Sickled RBC cannot move easily through blood
Get stuck in capillaries
Possibly fatal

13. Albinism Show relationship between gene, enzyme, and phenotype
Albinism melanin (dark pigment) totally or partially missing from eyes, skin, and hair
Causes:
Pale blue/pink irises
Pale skin
Pale hair
Red pupils
Poor vision
Jerky movements
Inability to absorb light (protection)
Genetic Cause:
Mutation at several LOCI
AUTOSOMAL RECESSIVE disorder
Must get TWO recessive alleles to have disorder
1 in births
SEX-LINKED version of disorder
Affects only eyes, not skin

14. TYROSINASE an oxidase enzyme
2 copper atoms in active site that bind to oxygen
Transmembrane protein
In membranes of large organelles in melanocytes called melanosomes
Most of protein, including active site in in melanosome
Also found in plants
Enzyme reacts with air (causes blackening of potato)
Enzyme TYROSINASE converts amino acid tyrosine into DOPA
DOPA is the converted to dopaquinone which is then converted into Melanin
Melanin:
dark brown to black pigment occurring in the hair, skin, and iris of the eye
responsible for tanning of skin exposed to sunlight
In Albinism:
Mutation of gene results in inactive or absent TYROSINASE
Without TYROSINASE, first two steps of conversion process cannot occur
No DOPA
No dopaquinone
No melanin

15. Huntington’s Disease (HD)
Autosomal Dominant Disorder
Most people with disorder are heterozygous
1 in 2 chance of passing it off to children
Neurological disorder
Causes involuntary movements (chorea) and mental deterioration
Age on onset is variable

16. Huntington’s Disease (HD)
Caused by mutation
Unstable segment in a gene on chromosome 4 that codes for protein HUNTINGTIN
Protein regularly interacts with proteins found only in the brain
Altered huntingtin is most disruptive to nerve cells, even though it is found throughout the body
Normal gene made of small number of repeats of the triplet of bases CAG
Mutated gene contain larger number of repeats of CAG triplet
STUTTER repeats of triplet
More stutters = earlier age in which condition appears