new material

mutation

any change in a DNA sequence

spontaneous mutations

mutations that occur under normal conditions, without the presence of a mutagen

induced mutations

mutations resulting from exposure to a mutagen from outside the cell

restrictive conditions

an environmental condition that prevents the expression of a mutant allele

permissive conditions

an environmental condition that allows the expression of a mutant allele

loss of function

a mutation that can lead to gene inactivation or a nonfunctional gene product

deletion or amino acid replacement

loss of function mutations are usually due to \_____________

hypomorphic

a mutation that reduces the expression of a gene, but does not terminate it

amino acid replacement

hypomorphic mutations are usually due to

hypermorphic

a mutation that results in a greater than normal level of gene activity

dominant

hypermorphic mutations usually occur with \________ genes

gain of function

mutation that causes gene activity in a scenario where there should not be any at all

ectopic expression

the expression of a wildtype gene in an abnormal location

nucleotide substitution

a mutation in which a single base pair in DNA has been changed

transition mutation

a nucleotide substitution in which a purine is replaced with another purine or a pyrimidine is replaced with another pyrimidine

transversion mutation

a nucleotide substitution in which a purine is replaced with a pyrimidine or vice-versa

transitions

are transversions or transition mutations more likely?

silent mutations

mutations that change the nucleotide sequence without changing the amino acid sequence

missense mutations

mutations that result in an amino acid change

nonsense mutations

mutations that cause a premature stop codon

frame shift mutation

additional, more severe mutation caused by an insertion or deletion

dynamic mutations

tandem repeats the end up increasing in size due to slippage of DNA polymerase

transposable elements

"jumping genes" that can transcribe themselves in and out of the genome

autonomous transposons

transposons that can transpose independently, as they can produce their own transposase

nonautonomous transposons

transponsons that need an autonomous transposon to provide the transposase in order for them to transpose

retrotransposons

transposable elements that use RNA as an intermediate for transposition through reverse transcriptase.

(Make RNA copy, converted to DNA, and put somewhere else)

ectopic recombination

can occur between two transposable elements and result in a deletion or inversion

hot spots

locations where mutations are likely to occur more frequently

deamination

the removal of an amino group from an amino acid due to high methylation

weak acids

mutagens that cause deamination of DNA bases and alters hydrogen-bonding specificity

depurination

the loss of a purine base from a nucleotide, adding adenine to the daughter strand. bond is broken through hydrolysis

alykylating agents

mutagens that can have very severe and numerous morphological effects, such as mustard gas or agent orange

ultraviolet radiation

mutagen that causes thymine dimers, or a covalent bond between two adjacent thymines, causing a kink in the double helix

ionizing radiation

mutagens such as x-rays or radioactive elements; can also be used to treat cancer

mismatch repair

repair in which the daughter strand is cut in two places and the region around the mismatched pair is removed

base excision repair

repair that removes damaged bases from DNA, leaving behind an a pyrimidinic site, where there is no base

AP repair

repair in which an AP endonuclease removes the baseless sugar left behind from the base excision repair, and the nicks are sealed by DNA ligase

nucleotide excision repair

removes stretches of DNA that is physically damaged

photoreactivation

reverses the kinks caused by thymine dimers by breaking the additional covalent bond; needs energy from blue light to happen

postreplication repair

repair in which DNA polymerase skips over damaged area during replication and the gap is filled with a strand exchange, which can later be used as a template strand to repair the damage

nonhomologous end joining

repair that seals the bonds broken during a double-stranded break

template directed gap repair

a repair in which the damaged part of a double-stranded break is cut out and a homologous DNA molecule is used as a template for repair

complementation test

similar to a test cross; used to determine if two mutations reside on the same gene

Any change in DNA

What are mutations?

Only way evolution can occur

Why are mutations important?

Evolutionarily Irrelevant

any mutation that impacts somatics bc it cant get through to next gen.

autonomous and non autonomous

2 types of transposable elements

autonomous

produces its own enzyme called transposase

non autonomous

does not produce it but can borrow transposase within family group

Retrotransposons

make RNA copy of itself then converts back to DNA and gets put somewhere else

(purple corn) They move around the genome into different locations. Can disrupt important genes by inserting into it and turn them off.

Why are jumping genes bad?

Mutations

are not predictable but can predict where they occur

Hot Spots

places with more C’s bc they can be methylated

slippage

Trinucleotide repeats bc of

What is a trinucleotide expansion disease and how is the "expansion" related to replication slippage

A trinucleotide expansion disease is a genetic disorder caused by the expansion of a repeated set of three nucleotides in a gene. a. DNA polymerase is doing the replicating. DNA polymerase slips and falls off. It gets back up in a different place than where it slipped. Bc it is a trinucleotide repeat it doesn’t know which repeat to jump back onto so it goes onto the wrong spot by mistake. fixes it

Polygenic inheritance

Many genes

Continuous

skin color

Categorical

number of offspring

Threshold

you have a trait but not might exhibit

Std dev sq is variance. Represents the variation around the central point

Characterizing a complex trait: mean, st. deviation, variance

Sources of phenotypic variation, how it’s partitioned.

genetics and environmental.

Genetic variation

differences in DNA sequence leads to differences in traits

Environmental variation

difference in trait because of different environment

Genotype-by environment interaction

when one genotype can have different phenotype in different environment.

genotype-by-sex interaction

same genes different outcome

how is narrow sense heritability further broken down?

\
Narrow sense heritability is further broken down into __additive genetic variance__ and __residual variance__. Additive genetic variance refers to the genetic variation that is passed down from parents to offspring and contributes to the resemblance between them. Residual variance, on the other hand, refers to the non-genetic factors that contribute to the variation in a trait.

\
Broad sense heritability

proportion of variance because of genetic factors.

\
narrow sense heritability

proportion of total phenotypic variation in a trait that is attributed to additive genetic information.

positive covariance

Positive covariance refers to a statistical relationship between two variables where they both tend to increase or decrease together. (more sleep better test score)

\
negative covariance

when one variable increases, the other variable decreases, and vice versa. (more partying bad grades)

Cancer is caused by mutations, usually somatic mutations. Even so, a common strategy for combating cancer is to give a patient drugs or radiation that causes even more mutations. Explain how this strategy works. Would this be a good strategy to prevent cancer?

Cancer is caused by mutations, usually somatic mutations. Even so, a common strategy for combating cancer is to give a patient drugs or radiation that causes even more mutations. This strategy works by targeting rapidly dividing cancer cells, which are more susceptible to DNA damage. However, this can also damage healthy cells and increase the risk of developing secondary cancers. Therefore, it is not a good strategy to prevent cancer, but rather to treat it once it has already developed.

Origin: spontaneous

occurs in absence of known mutagen

Origin: non spontaneous

occurs in presence of known mutagen

cell type: somatic

occurs in non reproductive cells

cell type: germ line

occurs in reproductive cells

Expression: Conditional

Expressed only under restrictive conditions

Expression: Unconditional

expressed under permissive and restrictive conditions

Effect on function: Loss of function

eliminates normal function

Effect on function: Gain of function (ectopic expression)

Expressed at incorrect time or inappropriate cell type

Effect on function: Hypomorphic (leaky)

reduces normal function

Effect on function: Hypermorphic

Increases normal function

Molecular change: Base substitution

1 bp in duplex DNA replaced with a different bp

Molecular change: Transition

Pyrimidine (T or C) to pyrimidine, or purine (A or G) to purine

Molecular change: Transversion

Pyrimidine (T or C) to pyrimidine, or purine (A or G) to pyrimidine

Molecular change: Insertion

One or more extra nucleotides present

Molecular change: Deletion

One or more missing nucleotides

Effect on translation: Synonymous (silent)

No Change in amino acid encoded

Effect on Translation: Missense (nonsynonymous)

change in amino acid encoded

Effect on Translation: Nonsense (termination)

Creates translational termination codon (UAA, UAG, or UGA)

Effect on Translation: Frameshift

Shifts triplet reading of codons out of correct phase

Most mutations in coding regions do result in amino acid changes

**nonsynonymous (missense) mutations**

Nicks in DNA strand

Repaired by DNA ligase

Chemically modified base

Base excision (removal by base-specific DNA glycosylase)

Mismatched bases

Corrected by mismatch repair

Apurinic or apyrimidinic site

Fixed by AP endonuclease

Damaged region of DNA

Nucleotide excision repair (excision and resynthesis across partner strand)

Pyrimidine dimers (from UV light)

Enzymatically reversed

Damaged region of DNA

DNA damage bypass (sequence in damaged region recovered via recombination)

mismatch repair

Mismatched base is detected. One of the strands is cut in two places. Region around mismatch is removed

which strand is cut? how do you know?

Daughter because it is not yet methylated so it is easier to cut. Because it is less methylated