Chapter 15 - Gene Mutations and DNA Repair

mutation

source of all genetic variation and many diseases/disorders

point mutation

mutation in which one letter of the code is changed

frameshift mutation

mutation in which letters are lost or gained in the code (except in multiples of 3)

base substitution

point mutation in which a base is swapped for a different base

missense mutation

change in DNA sequence results in a different amino acid being encoded at a particular position in the resulting protein

nonsense mutation

change in DNA sequence that a triplet codon is changed to a stop codon resulting in termination of translation of the protein

silent mutation

change in DNA sequence that changes the triplet codon but does not result in a change in amino acid of the protein

non-coding regions

what regions are most mutations more likely to occur at

neutral mutations

mutation that does not affect gene production or gene expression

most silent mutations can also be referred to as neutral mutations, BUT some silent mutations may alter DNA sequences that code for regulatory function

relation between silent and neutral mutations

• transition: pyrimidine replaces pyrimidine OR purine replaces purine

• transversion: pyrimidine replaces purine OR vice versa

2 types of base substitutions gene mutations

base substitutions, insertions, and deletions

3 basic types of gene mutations

loss of function

reduces or eliminates the function of the gene product

null mutations

mutations that result in complete loss of function

recessive mutation (most loss of function mutations)

results in WT phenotype when present in diploid organisms and the other allele is WT

dominant mutations

results in a mutant phenotype in diploid organisms even when the WT allele is also present

dominant negative mutation

1 allele may encode a gene product that is inactive and directly interferes with the function of the product of the WT allele

dominant negative mutation and haploinsuffiency

2 types of dominant mutations

gain of function (typically dominant)

mutation codes for a gene product with enhanced, harmful, or new functions

• change in amino acid sequence that confers new activity

• mutation in regulatory regions of the gene leading to expression of the gene are high levels or at abnormal times/places

2 ways mutation can cause gain of function

suppressor mutation

a second mutation that either reverts or relieves the effects of a previous mutation

intragenic

suppressor mutation occurring within the same gene that suffered the first mutation

intergenic

suppressor mutation occurring elsewhere in the genome

tri-nucleotide repeats

abnormal expansion of repetitive sequences that primarily affects the nervous system

• DNA molecules has high number of copies of a repeat

• the strands separate and replicate

• due to the high number of repeats, a hairpin forms on the newly synthesized strand causing part of the template strand to be replicated twice

• the strands separate and the new strand serves as a template for replication resulting in more copies of the already present repeat

explain how trinucleotide repeats arise

conditional mutation

a mutation has the WT phenotype under certain permissive environmental conditions and a mutant phenotype under other (restrictive) conditions

Cre-RE (recombinase)

can excise DNA sequences between 2 loxP sites

TAM (tamoxifen)

is needed to activate Cre

• somatic mutations occur in nonreproductive cells - offspring has population of mutant cells

• germ-line mutations occur in cells that give rise to gametes - ½ offspring all cells carry mutation and ½ offspring no cells carry mutation)

somatic vs germ-line mutations

• frequency of changes in the DNA

• probability that any changes will be repaired

• probability that it will be detected

3 factors affecting mutation rates

mutations resulting in evolutionary change and adaptation to new environments or stressful conditions

what are adaptive mutations

tautomer

alternate chemical form which differs by the shift of a single proton in the molecule

they allow for hydrogen bonding with non-complementary bases

what do tautomers allow for

causes nonstandard base pairings (due to flexibility in DNA structure) leading to mutant DNA once the “incorrectly” paired strand is replicated

what does wobble base pairing cause in terms of replication