Bio 309F. Chapter 11 Mutations: The Source of Genetic Variation
1. Mutations affect protein structure and function
A. Daughter with two mutations in beta hemaglobin chain (amino acid #6 leucine to valine and aminoacid #68 leucine to phenylalanine. RBC sickle and severe hemolytic anemia
B. Daughter inherited normal allele from mother and #6 mutant allele from father + #68 mutant occurred in sperm since father did not have this mutation
2. Introduction to mutations
A. Definition: Heritable change
B. Types: 1. Chromosomal, 2. DNA sequence alterations
C. Detection: 1. Dominant mutations, 2. Recessive mutations
D. Mutation rates for specific genes--measurement
3. Mutagens
A. Radiation--H.J. Muller
1. Chromosomal breaks (deletions, translocations, inversions)
2. Sources: Radon = 55%; Medical = 11%, Cosmic = 8% (360 mrem/yr)
B. Chemicals: Proflavin--Dye, Nitrous acid, . 5-Bromouracil
4. Tests for chemical mutagens
A. Bacteria: Ames “his” test
B. Fungi
C. Plants
D. Insects
E. Somatic cells in culture
F. Animals (mice and chickens)
5. Effects of mutations
A. Variation
B. Polymorphisms
C. Beneficial/Harmful
6. Examples of mutations
A. missense - CTC--->CAC (glutamic acid---->valine) (sickle cell anemia)
B. nonsense - AAA--->UAA termination codon
C. sense - UAA---> AAA--removal of termination codon
D. frameshift
Insertion: CAT CAT CAT GCA T
Deletion: CAT CAT CAC AT
E. trinucleotide repeats
1. Fragile X syndrome CGC--230 repeats
2. Myotonic Dystrophy CTG--50 to 2,000 repeats
3. Huntington Disease CAG--42 to 100 repeats
7. Example of chemical mutagen
A. 5-Bromouracil A:T----->A-5-Br ----> A:T G-5-BR
B. Benzo[a]pyrene and metabolites
C. Aflatoxin B--fungi on peanuts and other foods
8. DNA Repair Genes: Example
1. UV damage--thymine dimers (excision repair)
2. Xeroderma Pigmentosum--thymidine dimer defect
3, Bloom Syndrome--DNA ligase defect
C. Reversible alterations to the genome: Genomic imprinting
D. Teratogens
1. Thalidomide, 2. Viruses--Measles, herpes virus II,
3. Folic acid deficiency--neural tube defects, 4. High levels of vitamin A-lysis of red blood cells, 5. Fetal alcohol syndrome