15 GENE MUTATION AND MOLECULAR MEDICINE

Mutation- a change in the nucleotide sequence of DNA that can be passed on from one cell or
organism to another

Mutations that occur at the nucleotide sequence level- can be classified by the specific
changes they cause in DNA and phenotypic effects in proteins

Mutations that occur at the chromosomal level- can be classified by the specific changes they
cause in chromosomes

Induced Mutations- Caused by mutagens

● Mutagens- environmental factors that alter DNA structure
○ EX: chemicals, radiation

“Mutation hot spots” occur wherebases are more susceptible to mutation

Somatic mutations-
● Occur in somatic (body) cells
● Passed to daughter cells in mitosis; NOT sexually produced offspring

Germ line mutations-

● Occur in the cells that give rise to gametes
○ A gamete passes these mutations at fertilization

* NOT ALL MUTATIONS AFFECT PHENOTYPES *

● Silent mutations- Usually do not affect protein function
○ May bin in a non-coding region, or code for the
same amino acid as the original
○ Commonly results in genetic diversity that isn’t
expressed
○ Silent mutations do not alter amino acid sequences
 Loss of function mutations:
● Gene may not be expressed at all, or protein doesn’t
function
○ Nearly always recessive

Gain of function mutation- Leads to

protein with altered function
● Usually dominant
● Common in cancer
○ The new protein may stimulate cell division

Conditional Mutation:
● Phenotype is altered only under certain (restrictive) conditions
■ EX. A protein may be unstable at high temperatures
○ Mutation is not detectable under permissive conditions
■ EX: Point restriction phenotype is Siamese cats

Reversion Mutation: Most mutations can be reversed by mutating a second time

● DNA reverts to the original sequence
● The phenotype goes back to wild type

Point Mutation- Change in a single nucleotide

● Result in the gain/loss/substitution of a single nucleotide
○ Two types of substitutions
■ Transition
■ Transversion
 ● The P.M. in the coding region of a gene will alter the mRNA sequence and may or may
not result in a change in the protein
○ Silent mutations do not alter amino acid sequences

Transition- Substitution of one puring for

the other, or one pyrimidine for the other

Transversion- Substitution of a purine for a pyrimidine, or vice versa

Missense Mutations- Result in substitution of one
amino acid for another protein
● M.M.’s may have no effect on protein
function
● OR… the protein functional efficiency may
be reduced but not *completely* inactivated

Sickle-Cell disease…
- Sickle allele differs from normal allele by one base pair, which alters one subunit
of hemoglobin

● Gain of function M.M.s can also occur:

○ P53 codes for a tumor suppressor, but certain mutations cause the protein to
promote cell division and prevent cell death

Nonsense Mutations- A base substitution results

in a stop codon somewhere in the mRNA
● Results in a shortened protein, which is
usually not functional
● If near the 3’ end, it may have no effect