Genetics Exam 2

When are there exceptions to Mendel’s rules?

• there is no dominant/recessive allele

• more than 2 alleles exist

• multiple genes are involved

• gene-environment interactions

What is pleiotropy?

When one gene contributes to several characteristics

The phenotype of the ___ determines the dominance relationship of the two alleles

heterozygote

Define complete dominance

The hybrid resembles one parent

Define incomplete dominance

The hybrid has an intermediate phenotype of the parents

Define codominance

The hybrid shows traits from both parents

Are dominant relationships always the same?

No, the relations are relative to the other allele and are unique to a pair of alleles

In a case of incomplete dominance where true-breeding heterozygous parents are crossed, what do the F1 and F2 generations look like?

F1: all identical intermediate type

F2: 1:2:1 genotypic and phenotypic ratio

In a case of codominance where true-breeding heterozygous parents are crossed, what do the F1 and F2 generations look like?

F1: all exhibit both traits

F2: 1:2:1 genotypic and phenotypic ratio

Discuss mutation and their frequency in gametes.

Mutations are chance, random alterations of genetic material

Gamete mutation frequency: 10^-4 to 10^-6

Define allele frequency and wild & mutant alleles.

It is the % of the total number of gene copies in a population

• wild type alleles are the most common

• rare alleles are considered a mutation, but they may become a wild type allele

Define monomorphic, polymorphic, and common variants.

Monomorphic: only one common wild-type allele

Polymorphic: more than one common allele

Common variants: high-frequency alleles of polymorphic genes

What is pleitrophy?

It is when a single gene determines distinct and seemingly unrelated characteristics. Homozygotes can be lethal.

Define genetic cascade.

The product of one enzyme is required for the next step.

What is the phenotypic ratio for a gene with recessive lethality?

2:1

Discuss epistasis.

It occurs when an allele at one gene masks the effects of another gene. The allele masking the gene is epistatic. The gene being masked by the allele is hypostatic.

Epistasis can be recessive to dominant. In a recessive case, the allele must be homo recessive. In a dominant case, one copy of the allele masks the other gene.

What are the reasons that phenotypical variation occurs?

• modifier proteins

• environmental effects

• chance

Define penetrance.

It is the percentage of individuals with a genotype that show that expected phenotype.

Define expressivity.

It is the degree or intensity with which a genotype is expressed in a phenotype.

What are modifier genes?

They alter the phenotypes produced by alleles of other genes.

Define heterogenous traits.

It is when they have the same phenotype but it is caused by mutations in different genes.

Define complementation testing.

It is when you determine if phenotype arises from a mutation in the same or different genes. It can only be done for recessive phenotypes.

What are additive gene interactions?

It is normal Mendelian inheritance where there are 4 phenotypes in the F2 generation with a 9:3:3:1 ration.

What are recessive epistasis gene interactions?

• When homozygous, the recessive allele of one gene masks both alleles of the other gene.

• 9:3:4

What are reciprocal recessive gene interactions?

• When homozygous, the recessive allele of one gene masks the dominant allele of the other gene

• 9:7

What are dominant epistasis I gene interactions?

• The dominant allele of one gene hides the effects of both alleles of the other gene

• 12:3:1

What are dominant epistasis II gene interactions?

• the dominant allele of one gene hides the effects of the dominant allele of the other gene

• 13:3

What are reciprocal/redudant dominant epistasis gene interactions?

• the dominant allele of each gene masks the effects of the recessive all of the other gene

• 15:1

What are conditional lethal mutation and what are the different conditions?

They are mutations that are only lethal under certain conditions.

Permissive conditions: mutant allele has wild-type functions

Restrictive conditions: mutant allele has defective functions

Define phenocopy/

A phenotype that a rises from an environmental agent that mimics the effect of a mutant gene, they are not heritable and can be deleterious or beneficial.

Define discontinuous traits.

Traits that show clear-cut, “either-or” phenotypic differences

Define continuous traits.

They are determined by alleles of many genes that interact with the environment and each other. They blend and unblend. They are considered quantitative traits if they vary over a measurable range.

What is a polygenic trait?

It is controlled by multiple genes

What happens in there are a greater number of genes/alleles that encode for a phenotype?

There is a more continuous distribution.

Define synthetic genes.

Genes that are located on the same chromosome

What is genetic linkage?

Genes that are inherited together. The 9:3:3:1 ratio is altered.

How is autosomal linkage detected?

Crossing a double heterozygote with a homozygous recessive.

What is used to identify chromosomes and points of reference for recombination?

Genetic markers

T/F: if recombination did not occur, nondisjunction in M1 would occur more frequently.

T

What is recombination frequency?

It is the % of progeny that are recombinant; can be used to measure physical distance

1 % RF = 1 m.u. = 1 cM

Discuss the recombination frequency of linked and unlinked genes.

The RF of unlinked genes is 50% due to independent assortment, The RF for linked genes is never greater than 50%.

Define loci.

A gene’s specific location on a chromosome

What are the limitations of a two-point cross?

• difficult to determine gene order

• actual distance between genes doesn’t always overlap

• time and labor consuming

Discuss the traits of a 3 point test cross.

The test cross progeny have 4 sets of reciprocal pairs of genotypes

• most frequent = parental type

• least frequent = double crossover

Can determine location of a gene

How do you correct for a DCO?

Add the DCOs twice because they represent two exchanges

Define chromosomal interference.

The occurrence of a crossover in one portion of a chromosome interferes with a crossover in an adjacent part of the chromosome. It is not uniform within or between chromosomes.

Define linkage group.

Genes that are connected by linkage relationships.

Why does physical distance not always correlate to physical distance?

• double, triple, ect crossovers

• 50% max recombination frequencies

• recombination hotspots

Why is interference important in terms of nondisjunction?

It ensures that there are recombination enzymes across all chromosomes.

What does it mean if interference equals 0 or 1?

0 = crossovers occur independently

1 = no double crossovers occur

What is the chi square test?

It measures the goodness of fit between expected and observed values.

What is a null hypothesis?

The observed values are not difference from the expected values.

The null hypothesis is that there is no linkage. The chi square test can reject the null, but cannot prove the hypothesis. There is an expected 1:1:1:1 ratio if there is no linkage. Cut off if 0.05, can reject null with 95% confidence

What information is needed for the chi square test?

• total number of progeny

• classes of progeny

• number of offspring in each class

Define mutations.

Heritable changes in the base pair sequence of DNA.

What is a forward vs reverse/reversion mutation?

Forward: changes wild-type allele to a different allele

Reverse/Reversion: changes a mutant allele back to wild-type, much less common

Discuss substitution mutations and the two different kinds.

Substitution is the replacement of a base by another base.

• transition: purine replaces by purine and vice versa

• transversion: purine replaced by a pyrimidine and vice versa

What is a deletion mutation?

Block of one or more base pairs is lost from DNA

What is an insertion mutation?

A block of one or more base pairs is added to DNA

What are point mutations?

They affect a small number of base pairs, like substitution, deletion, and insertion mutations.

How often does a given gene mutate to a recessive allele?

11 in a million (10^6)

What affects mutation rates?

• differences in gene size

• susceptibility of particular genes to various mutagenic mechanisms

Discuss the mutation rate in prokaryotes vs eukaryotes and haploids vs diploids.

Mutation rate is higher in gamete-producing eukaryotes because many cell divisions can take place between zygote formation and meiosis, giving them more changes to accumulate mutation.

Diploid organisms can better tolerate mutations than haploid organisms because they have a second copy of a chromosome that can mask the mutation.

What is the estimated mutation rate in humans and how many mutations does each child have?

Mutation rate is estimated to be around 1×10^-8

Each child contains roughly 60 mutations, but most don’t influence phenotype because they are masked for heterozygous individuals

What is the mutation rate in sperm and why is it higher?

2^-4 × 10^-8

Because male sperm undergo mitosis continually, more mutations in sperm from older fathers

What experiment found that mutations in bacteria occur spontaneously?

Wild-type bacteria were infected with a phage. Most of the cells died, but some survived.

The 1st hypothesis that resistance is a response would require there to be roughly equal amounts of mutant bacteria in the different groups of the generation that the infection appeared in.

The 2nd hypothesis that resistance is from random mutation would require there to be different numbers of individuals with the mutation in the different groups and the parent bacteria would also need to posses it.

It was found that different amount of colonies grew, supporting hypothesis 2

How did replica plating help confirm that bacterial resistance is the result of preexisting mutations?

The plate with colonies is stamped from one plate to another, then grown in penicillin medium. The resistant colonies that grew could be identified and traced back to parent colonies.

The bactericide functioned as a selective agent.

Discuss depurination and deamination.

Depurination: the hydrolysis (removal) of a purine base that occurs 1000/hr in every cell

Deamination: removal of an amino groups that can change C to U

How does UV, X-rays, and cosmic rays affect DNA?

X-rays and cosmic rays can break the sugar-phosphate backbone of DNA

UV light causes adjacent thymines to form abnormal covalent bonds (thymine dimers)

What does oxidative damage look like in individual bases?

8-oxodG mispairs with A

GC → TA

Discuss DNA polymerase and proofreading.

DNA poly incorporating incorrect bases is rare, 1×10^-9

Proofreading portion of the molecule is 3’ to 5’ exonuclease, which recognizes and excises mismatches

Discuss tautomerization and mutations

Each base converts between tautomers, which are similar chemical forms and this can cause incorrect base matching because they are in the wrong conformation

What are trinucleotide repeats?

They are 3 repeating base pairs. They can slip, misalign, or add a lot of copies of the repeating nucleotide sequence and cause a mutation

Define mutagens.

Agents that raise the frequency of mutations above the spontaneous rate.

Discuss thee experiment that exposed X-rays to flies.

Male flies were exposed to x-rays that mutated a gene on their x chromosome. All female progeny got the mutation and male progeny got the wild-type from their mother.

What are base analogs?

Molecules with a chemical structure that is almost identical to a normal DNA base. These can replace bases.

How do base analogs cause mutations?

They induce a chemical or structural change. The analog replaces the true base but when replication occurs it is not correct. Alkylation, hydroxylation, and deamination are examples.

What are intercalators?

Compounds that physically insert itself into the DNA helix. This can result in the random indexation or deletion of base pairs.

Describe the Ames test.

It is a test used by the FDA to screen for chemical that might cause mutations and therefore cause cancer. Recessive mutants are exposed to the mutagen and plated into a medium without nutrients. If many colonies grow, that shows that the mutagen is strong because reverse mutation has occurred.

List the accurate repair system and the error-prone repair systems.

Accurate:

• reversal of DNA base alteration (ase)

• homology-dependent repair

  • base excision

  • nucleotide excision

• double-strand break repair

  • homologous recombination

  • non homologous end-joining

Error:

• SOS system

  • sloppy, adds random nucleotides, stalled replication forks

• MMEJ

  • joins together double-strand break, but there are some small deletions

Discuss the homology-dependent repair systems.

Base excision:

• altered base is removed along with nearby nucleotides

• new DNA synthesized to fill the gap

• relevant for uracil removal

Nucleotide excision:

• UvrA + UvrB complex scans for distortions like thymine dimers

• Damaged DNA removed

• new DNA synthesized to fill in the gap

Discuss the double-strand break repair systems.

Homologous recombination and nonhomologous end-joining

• unprepared double-strand breast can lead to deletions and chromosome rearrangements

• these join the ends back together

How do bacteria identify the original strand?

In parental strands there is methylated DNA where GATC occurs that signals that it is the original

What is complementation testing?

Reveals if two mutations are in a single genes or indifferent genes. If the phenotype is wild-type when two mutations are present on different homologs, they must be in different genes.

If two mutations fail to complement they are on the same gene.

What is a complementation group?

A gene

What is the one gene, one enzyme hypothesis experiment?

Bread mold was used to study the relationship between genes and enzymes. They tested if different mutations blocked different steps in arginine synthesis. Arginine aucotrphs were grown in the presence of chemical intermediates. This allowed scientists to infer the biological pathway.

What are prototrpohs vs auxotrophs

Pro: wild-type that grows in minimal media without nutritional supplements

Aux: mutant strain that cannot grow in minimal media, requires supplementation

What is a missense mutation?

A genetic alteration that substitutes one amino acid for another.

How many nucleotides are in one codon and how many combinations are there?

3 nucleotides in one codon

64 combinations

What is a frameshift mutation?

A changing of the grouping of nucleotides as a result of an insertion or deletion.

What are nonsense codons?

They are stop codons.

UAG, UAA, UGA

What two events reshape genomes?

1. rearrangements - DNA sequences are reorganized within one or more chromosomes

2. chromosome number changes - loss/gain of entire chromosome

What are the four types of chromosomal rearrangement?

Deletions/ duplications

• adding/removing base pairs

Inversions/ reciprocal translocations

• relocating chromosomal regions without changing the number of base pairs

Is FISH or SKY better for identifying chromosomal translocation or deletions.

FISH - deletion

SKY - translocation

Discuss deletion heterozygotes.

• mutant phenotype due to gene dosage effects

• increases risk of phenotype due to mutation in other copy of gene

• may uncover existing recessive mutant alleles

How can deletions be used to locate genes?

Something like a complementation test can be performed. If a heterozygote for a recessive mutant allele has a deletion in the gene region, it can expose the location of the allele. If the mutant allele was in the deleted region, the phenotype would be mutant because the masking allele was deleted.

T/F: Recombination between homologs can only occur at regions of similarity.

True

T/F: Recombination cannot occur within a deletion loop.

True

How does a deletion loop affect recombination?

The deletion loop loops the region of deleted genes in the other chromosomes. It allows parts on both chromosomes to align.

How do deletions affect phenotype?

Most duplications have no phenotypic consequences. Novel phenotypes can occur due to increased gene copy number/altered expression in a new chromosomal environment.

What are the types of duplications?

Tandem (next to each other) and nontandem/dispersed (not next to each other)

They can be in the same order or reversed order.