Mutation: a change in the nucleotide sequence that composes a gene. This is a change or variation from the most common or wildtype sequence.
A mutant allele is an allele that differs from the common allele in the population (also called the wildtype allele).
A mutant phenotype refers to a phenotype that differs from the common or wildtype phenotype.
Mutations are not good or bad, just different from the majority in the population.
are mutations that occur in cells of the body
excluding the germline. Affects
subsequent somatic cell descendants. Limited to impact on the
not transmitted to offspring.
Germline mutations: The change occurs during the DNA replication that precedes meiosis. The resulting gamete and all the cells that descend from it after fertilization have the mutation.
II. Mutations can alter
proteins -- three examples:
Genotype to disease phenotypeCystic fibrosis disease CFTR protein
III. Causes of
1. Spontaneous mutation (De novo or new mutations: not caused by exposure to known mutagen)
Errors in DNA replication: DNA bases have slight chemical instability (exists in alternating forms called tautomers)
III. Causes of Mutation:
Sequence dependence, and Hot spots
Viruses mutate rapidly.
Influenza vaccines are reassessed each season to accommodate viral changes.
Rapid mutation of HIV virus makes treatment difficult.
Chemicals and radiation can cause mutations. Chemicals causing mutations are called mutagens. Chemicals causing cancer are called carcinogens.
Acridine dyes: add or remove base
Xrays: break chromosomes
delete few nucleotides
UV radiation: creates thymidine dimers
IV. Types of Mutations:
A point mutation is a change of a single nucleotide to one of the other three possible nucleotides
purine replaces purine
A -> G or G -> A
pyrimidine replaces pyrimidine
C -> T or T -> C
purine replaces pyrimidine or
pyrimidine replaces purine
A or G -> T or C
T or C -> A or G
A point mutation that exchanges one codon for another causing substitution of an amino acid. Missense mutations may affect protein function severely, mildly or not at all.
Hemoglobin mutation : glutamic acid -> valine causes sickle cell anemia
Nonsense mutation: A point mutation changing a codon for an amino acid into a stop codon (UAA, UAG or UGA).
Most common cause of factor XI deficiency is a nonsense mutation change glutamic acid to a stop. Short protein cannot function in clotting.
Insertion or deletion mutations
Addition or subtraction of nucleotides not in
three lead to a change in the reading frame used for translation. Amino
after that point are different, a phenomenon called a frameshift.
Addition or subtraction of nucleotides in multiples of three leads to addition or subtraction of entire amino acids but not a change in the reading frame.
Two-thirds of Duchenne musular dystrophy cases are large deletions.
Gaucher disease is caused by a single base
creating a frameshift.
A tandem duplication is a particular form of insertion in which identical sequences are found side by side.
Myotonic dystrophy: a triplet repeat disease
5 -37 copies of CTG repeat normal phenotype
50-1000 repeats myotonic dystrophy
A pseudogene is a DNA sequence reminiscent of a gene but which is not translated (may or may not be transcribed).Not all mutations impact protein function
V. DNA Repair