• A good overall background about DNA and mutations from the Access Excellence web site.
• Mendelian Genetics Directory
• Reading the Messages in Genes from Access Excellence
• Deformed frogs
  
• Head lice
  
• Herbicide resistance
  
• and of course, the ultimate in mutations.

1. Define what a mutation is, and how mutations occur.

2. Distinguish between germinal and somatic mutations and describe the consequences of each.

3. Describe the types of mutations that can occur in a gene and the effect, if any, they have on the protein that is produced when the gene is expressed.

A mutation is any physical change in the genetic material (such as a gene or a chromosome). A mutation is not necessarily bad (it may even be good).

Chromosomal Mutations

• Changes in chromosome structure
  deletions, duplications, inversions, translocations

• Changes in chromosome number (this link takes you back to lecture 12)
  polyploidy, autosomal aneuploidy, sex chromosome aneuploidy

Gene Mutations

• Damage may occur at any time in any cell. Mutations result when the damaged genes are replicated without repairing them first.
  • Chromosome replication is 99.999% accurate. Errors in the actual duplication process happen only about once in 100,000 bases.

  • However, the human genome has about 6 billion bases. That means each replication cycle will have 6,000 errors associated with it!

  • In addition, damage to chromosomes may occur for other reasons, such as:
    • exposure to certain chemicals

    • exposure to ionizing radiation, including ultraviolet rays or radioactivity

    • exposure in utero to teratogens such as alcohol, cocaine, carbon monoxide, accutane (acne medicine), German measles, pseudoephedrine, tetracycline, lead, mercury, and many more.

• DNA repair is also possible. Indeed, it is the rule.
  • Cells contain several complex systems to fix damage before, during, and after replication. As a result, DNA replication and repair disorders are pretty rare (see text, pp. 319-322).

• Mutations are not always bad, even if they aren't good.
  • The amount of DNA you have is much greater than that accounted for by your genes. Even with 50,000 proteins and a daily production rate of billions of protein molecules, the vast majority of your DNA is not involved in protein coding.

  • Within an allele, as much as 95% of the DNA is non-coding. Introns get clipped out before protein synthesis starts.

  • Mutations in non-coding regions usually do nothing to the phenotype of the individual.

  • Within the coding regions of alleles, some types of mutations have no effect on the resulting proteins.

• Mutations do much more than cause birth defects and genetic disorders. They do not occur only in humans.
  • Mutations are a way to introduce new alleles into a population. This means, mutations increase the genetic variability of a population.

  • Genetic variability is essential to the process of evolution and the formation of new species. Without mutations in the genetic material of some earlier primate species, we would not be here.

• In spontaneous mutations, DNA sequences are altered for no apparent reason, usually due to a DNA replication error.
  • One type of error is the substitution of one base (an A or G) for another (a C or T).

  • Spontaneous mutations are more rapid in those organisms with very short generation times than in those with long generations.

• In induced mutations, DNA sequence changes occur as the result of exposure to mutagens.
  • Note: UV light is a mutagen that you should think about before hitting the beaches or the tanning salons to get your suntan.

• Mutations can occur either in cells undergoing mitosis or meiosis.

• Cells in an organism's body, any cell except a sperm or ovum, are somatic cells.
  • Somatic mutations early in development may be very important in the entire development process.

  • Somatic mutations later in development may result in unusual growth, e.g. cancer.

  • Somatic mutations result in an individual not being genetically uniform.

• Mutations in sex cells, before meiosis, results in genetically altered gametes. Such mutations are called germinal and are carried to all the cells which descend from it following fertilization.

• There are many ways that mutations can occur and affect gene expression! To understand them really, you need to refamialiarize yourself with the genetic code (text, p. 333).

• Point mutations - changes in single DNA nucleotides.
  • A missense mutation substitutes a different amino acid for the original one.

  • A nonsense mutation results in a stop codon being inserted.

  • Silent mutations are point mutations that do not change the amino acid. They are the most likely to have no effect.

• Change in numbers of nucleotides - additions or deletions of one or more nucleotides
  • Frameshift mutations result in "garbage" genes. The entire amino acid sequence in the code after the change is devastated.

  • Larger deletions may just remove a single amino acid, or an entire chunk of chromosome.

  • Some genes have repeated base sequences, and the number of these may increase in each generation. These expanding genes are responsible for increasingly severe cases of muscular dystrophy (CTG repeats), Huntington disease (CAG repeats) and Fragile X syndrome (CGG repeats).

Wild type	THE ONE BIG FLY HAD ONE RED EYE
Missense	THQ ONE BIG FLY HAD ONE RED EYE
Nonsense	THE ONE BIG
Frameshift	THE ONE QBI GFL YHA DON ERE DEY
Deletion	THE ONE BIG HAD ONE RED EYE
Duplication	THE ONE BIG FLY FLY HAD ONE RED EYE
Insertion	THE ONE BIG WET FLY HAD ONE RED EYE
Expanding	(P) THE ONE BIG FLY HAD ONE RED EYE
Expanding	(F1) THE ONE BIG FLY FLY FLY HAD ONE RED EYE
Expanding	(F2) THE ONE BIG FLY FLY FLY FLY FLY FLY HAD ONE RED EYE

• Summary of CF Mutations
• The Perils of Antiobiotic Resistance and Antibiotic Resistance from American Scientist
• Human Gene Mutation Database
• Hemoglobin Mutants

Take me away.