Genetics exam 2

conditional expression of phenotype

phenotype only expressed under restrictive conditions

unconditional expression of phenotype

phenotype expressed under any conditions

Null mutation

mutation that eliminates normal function or expression (loss of function)

Hypomorphic mutation

mutation that reduces normal function (loss of function)

hypermorphic mutation

mutation that opposes normal activity (gain of function)

pyrimidines

Cytosine and Thymine, one ring

spontaneous mutations

occurs in the absence of a known mutagen (occurs without the mutagen needing to be there)

induced mutation

mutation that occurs in the presence of a known mutagen ex.radiation

somatic cell mutations

mutations that occur in non-reproductive cells

germ-line cell mutations

mutations that occur in reproductive cells (ex. X-linked cells)

Purines

Adenine and Guanine, two rings

Base Analogs

Mimics one of the base pairs with wrong complementary base and causes GC-> AT or AT-> GC transitions. Causes point mutations

ex. 5-bromouracil - can mimic T or C

Alkylating Agents

methyl groups added to oxygens on bases, which changes base pairing and causes GC->AT or AT-> GC transition. Causes point mutations

ex. EMS (ethyl methane sulfonate) mutagenesis

Intercalating Agents

Aromatic rings that are similar to bases, and fit in between bases in the DNA helix and trick DNA polymerase into adding an extra nucleotide. Causes frameshift mutations

ex. Proflavin, Ethidium Bromide, acridine orange

UV radiation

Irradiation causes thymine dimers to form, which blocks DNA replications. Ex. UV light

Ionizing Radiation

Irradiation causes double and single stranded breaks in DNA, which lead to errors during DNA repair and base damage via Reactive Oxygen Radicals ex. x-rays, gamma rays

cystosine deamination

cytosine loses an amine group and becomes uracil, 5-methylcytosine would become thymine

Trinucleotide repeat extension

strand slippage - when highly repetitive sequences on a DNA strand either bind themselves instead of the parent strand, or bind upstream from where they are supposed to. Slip-back results in insertion (expansion), and slip-forward results in deletion.

Transposons

mobile DNA sequences that integrate into various sites in the genome via non-homologous recombination

non-homologous recombination

recombination of double strand break of DNA but with no sticky ends, so no need for the two strands to match

Why is deamination of 5-methylcytosine worse than if it happened to normal cytosine

because a deaminated of 5-methylcytosine will turn into thymine, which naturally occurs in DNA, whereas cytosine would turn into Uracil, which only occurs in RNA. Uracil is easily detected as a mistake in DNA and will be quickly found and fixed by the cell.

How does water deaminate DNA?

Water would create a carbonyl (or ketone) group on the cytosine where there was originally an amine group. This occurs via hydrolysis with water

DNA-excision repair steps

1. Damaged DNA recognized by enzymes

2. Nicks created on ends of damaged segment

3. Segment is removed and degraded

4. DNA polymerase re-synthesizes DNA based on un-damaged strand

5. Ligase repairs remaining nicks

base excision repair

removes a mismatch by eating away one base, and then removing the backbone. DNA polymerase then fills the gap and DNA ligase repairs the nicks left over

How is deamination repaired?

by base-excision repair

Which strand is repair biased towards and why?

repair is biased towards the original strand, because the parent strand is recognized through methylation in prokaryotes. In eukaryotes, the parent strand is recognized because the daughter strand has nicks.

barr body

a disabled X chromosome

a quadruplex

a single strand structure folded in on itself

Drosophila X-linked test

the most sensitive test for mutation is the number of genes that can show that mutation. ex. look at relationship between x-ray dose and frequency of X-linked recessive lethal mutations

Microbial dosimetry

treat yeast with mutagens and see how many survive. aka survival test

Methods for detection of Environmental mutagens

Microbial dosimetry, Drosophila X-linked lethals, Ames Test

Ames test

assay for mutations using base substitution and frame shift mutation - input yeast with a frameshift mutation, and then treat the yeast with mutagens until there is a mutagen that undoes the original mutation (pseudo reversion). This creates a revertant population. This test is a sensitivity assay for mutation induction on bacteria, to see how mutagenetic difference compounds are (like cigarette smoke). Produces a linear dose response, so compounds can be compared

Why is liver extract important in Ames Test

because many carcinogens cannot do damage until metabolized in the body, liver extract is important in the ames test to activate carcinogens to allow mutation to occur

1st division segregation (Neurospora)

genes separated in meiosis 1 - pattern will be half and half

2nd division segregation (Neurospora)

genes separated in meiosis 2 - will looked like striped patter

What is evidence of gene conversion

When the ratio of phenotypes in neurospora spores is not 1:1

5' resection

when a double stranded break is made in a holliday junction, the 5' ends are eaten

strand invasion

the entry of the 3' end of a displaced DNA into an intact sister chromatid

Spo11

makes the double stranded break in holliday junction

asymmetrical cleavage

if you cleave a holliday junction on the inside, and twice on the outside, it will make a crossover event, and there will be recombination

Holliday junction

cross-shaped structure that forms during the process of genetic recombination, when two double-stranded DNA molecules become separated into four strands in order to exchange segments of genetic information.

suppressor

a mutation that reverses the phenotype causes by another mutation

intragenic suppressor

a suppressor that lies in the same gene as the initial mutation

extragenic suppressor

a suppressor that lies in a different gene from the initial mutation

psuedorevertant protein

a protein that has two mutations: one mutant and the other a suppressor, so they cancel out and the protein acts normally despite having two mutations

Where does Ames Test sensitivity come from

Ames test sensitivity comes from pseudo reversion - start with a gene that has a lethal frame shift, and treat the yeast with mutagens until there is a mutation that reverses the frameshift, either through true revertant (reverse the original damage in the same spot)(back mutation), or pseudo revertant (add a mutation later in the gene that restores the frameshift, but will leave a section of the genome out of shift)(suppressor mutation)

CpG cluster

where we can find an abundance of 5-methyl cytosine - eukaryotes methylate CpG dinucleotides that are congregated together for the purpose of gene regulation

nucleotide excision repair

A repair system that removes and then correctly replaces a damaged segment of DNA using the undamaged strand as a guide.

How are thymine dimers repaired

by nucleotide excision repair

aneuploidy

abnormal chromosomal ratio

trisomy

one extra chromosome

monosomy

one less chromosome

How many chromosomes do humans have?

46 - 23 from mom, 23 from dad

mosaicism

one X is turned into a Barr body and other is used and expressed, leads to mosaic of parental X chromosome across the body

dosage compensation

an organism shuts off gene expression in one or more copies of a gene so the gene is expressed at the appropriate time. Ex. Barr body

transition mutation

pyrimidine to pyrimidine, or purine to purine

transversion mutation

pyrimidine to purine, or purine to pyrimidine

missense mutation

change in amino acid

nonsense mutation

an amino acid turned into a stop codon

How is a deletion mutation be inherited with cross over

two genes many have a lower frequency of recombination, if there was a section of the genome deleted from the middle of them

How is a duplication mutation inherited with cross over

can mediate unequal crossing over which can change chromosome structure

paracentric inversion

crossing over that does not include the centromere - if crossing over does occur, then a dicentric chromosome forms and an acentric fragment is lost.

Only have 2 viable products, and two inviable

pericentric inversion

inversion where the centromere is included

makes two unbalanced products which may yield inviable or non-productive gametes

protanomaly

a defective hybrid gene, for ex a gene that is half red and half green, means the person is color blind

deuteranomaly

a protanomaly gene with both intact genes, but also a hybrid gene in the middle

interchromatid crossover

When a gene crosses over itself, making a protanomaly of gene, and a loop with the hybrid gene on it that just gets digested

what are the two different methods to analyze the encoding function of genes

forward genetics and reverse genetics

Forward genetics

conducted by observing effects of genetic mutations, then try to trace back where the mutation occurred

Reverse genetics

conducted by inserting a mutation at a specific spot in the genome and seeing how it affects the genotype of the cell

genetic selection

only let progeny of specific genotype survive

genetic screening

let some cells survive, but then screen them for mutations and desired phenotype

concatemer

a series of repeating DNA sequences ligated together with non-homologous end joining - ex. if you try to insert a drug marker, it may accidentally insert itself multiple times in a row in one gene

Translocation

Without crossover, either 4 viable or inviable, with crossover 2 viable, 2 inviable

Differences in how the chromosomes separate in the cell may cause crossing over - segregate in + formation vs x formation

If two offspring viable, 2 inviable, what mutation likely occurred?

Inversion mutation