Genetics Final- Problem Sets and Powerpoints

What is a mutation?

A change in genetic material (DNA) and the process through which it occurs

What are mutants?

Phenotypes resulting from mutations

Compare chromosomal and point mutations

Chromosomal mutations involve changes in the number or structure of chromosomes and often affect a large number of genes (greater effect); Point mutations affect one nucleotide and affect one or a few genes

What are polyploids? How do they affect the dosage of genes?

Mutation where the entire genome is duplicated (can occur through incomplete mitosis or meiosis), can result in sterile organisms; dosage remains unaffected because the gene ratios stay the same

What is an aneuploidy? How do they affect the dosage of some genes?

The gain or loss of some chromosomes, occur when chromosomes fail to separate (nondisjunction); changes the dosage of some genes which can lead to more issues

What are duplications? What are deletions?

Duplications- segments of chromosomes are duplicated

Deletion- segments of chromosomes are deleted

What are inversions?

Segment of a chromosome is “flipped”

What are translocations and insertions?

A segment of a chromosome is detached and reattached to a non homologous chromosome

What are the three types of point mutations at the mRNA level?

Substitution- occurs when one base pair is substituted for another

Insertion- occurs when a base pair is inserted into the DNA strand

Deletion- occurs when a base pair is removed from the strand

What are the four types of point mutations at the protein/peptide level? What are the effects?

Silent mutations- no effect on protein due to redundancy in genetic code

Missense mutations- result in one amino acid change in peptide

Nonsense mutations- result in premature stop codon

Frameshift mutations- result from changes to one or two base pairs, disrupt the reading frame of entire peptide

Are all mutations inherently bad?

No, mutations are not inherently bad. The overwhelming majority of mutations occur in noncoding DNA, which has a neutral effect on the genome. Mutations are the basis of all biological variation. They are essential to the diversity of life, even if they are usually negative when they have effects.

Two mutations occur in the same gene: one is a missense mutation in exon 1, and the other is a silent mutation in exon 3. Which is more likely to affect protein function? Why?

The mutation in exon 1 is more likely to affect protein function because A missense mutation changes one amino acid in the protein sequence. Because exon 1 is at the beginning of the coding region, this altered amino acid is likely located in an early, potentially critical part of the protein—such as a structural domain required for folding or an active domain necessary for function. A silent mutation does not change the amino acid sequence due to redundancy in the genetic code. Even though it occurs in exon 3, the resulting protein remains unchanged, so it is unlikely to affect protein function.

Consider a gene encoding a protein essential for cellular respiration. Describe how each of the following point mutations could affect the function of the resulting protein: silent, missense, nonsense, and frameshift mutations. Which mutation is likely to have the most severe impact on protein function, and why?

Silent mutation: changes a nucleotide without altering the amino acid sequence. This usually has no effect on protein function.
Missense mutation: changes one amino acid in the protein. Its impact depends on the role of the altered amino acid; it could range from negligible to significant if it affects critical regions.
Nonsense mutation: converts a codon into a stop codon, producing a truncated protein. This usually results in a nonfunctional protein, as essential parts are missing.
Frameshift mutation: adds or deletes nucleotides, shifting the reading frame and altering all downstream amino acids. This typically results in a completely nonfunctional protein.
Frameshift mutations are generally the most severe as they disrupt the entire amino acid sequence beyond the mutation, often yielding a nonfunctional protein essential for cellular respiration

Compare spontaneous and induced mutations

Spontaneous mutations occur for no known reason as the “background” rate of mutations. These can result from DNA replication errors or lapses in DNA repair mechanisms. Induced mutations occurs when an organism’s DNA is exposed to mutagens that affect the DNA sequence

What are mutagens? What are the three types?

Environmental factors that cause mutations; chemicals, radiation, and transposable elements

What are chemical-inducted mutations? What are the two types?

Mutations that affect replicative DNA; Base analogs- purines and pyrimidines with similar structures to DNA bases, incorporate into DNA during DNA rep, cause mispairing mutations during replication due to structural differences; Acridine dyes- intercalate between DNA nucleotides, increase likelihood of replication errors

What chemicals can also affect nonreplicative DNA?

Nitrous acid- causes oxidative deamination of amino groups in A, G, and C, alters H bonding with complementary base; Alkylating agents- donate alkyl group to DNA, causes widespread mutations because of reactive DNA

How are alkylating agents used in cancer treatment?

Chemotherapy; cancer cells replicate more often than normal cells and are more susceptible to damage by alkylating agents

What are radiation-induced mutations? What are the two types?

Nonionizing- lower energy, can’t penetrate into deep tissue (ex. UV), excites electrons in skin cells, can induce changes in nitrogenous bases

Ionizing- higher energy, can penerate tissues (ex. X-rays), cause release of electrons from atoms which creates free radicals and ions which can affect molecules in DNA

What are somatic mutations? What are germline mutations?

Somatic mutations- occur is normal body cells, may result in cancer

Germline mutations- occur in gametes or zygotes (heritable mutations)

Mutations occur at random. How does this apply to the evolution of antibiotic resistance in bacteria?

Bacteria does not gain the mutation for the purpose of surviving antibiotics. Instead, this mutation occurs at some rate in the genome, and when exposed to antibiotics, some bacteria will have the mutation and some will not.

Describe how a single base change in DNA could alter the amino acid sequence of a protein and ultimately a cell’s phenotype. Include the steps of transcription and translation in your explanation

A single base change in DNA can alter a protein and the cell’s phenotype by changing the flow of information from DNA → RNA → protein. During transcription, RNA polymerase copies the mutated DNA into mRNA, so the altered base becomes part of a codon. During translation, the ribosome reads this changed codon, which may lead to a different amino acid being incorporated (missense), a premature stop codon (nonsense), or a shifted reading frame (frameshift). Any change in amino acid sequence can affect how the protein folds or functions. If the protein works differently—such as losing activity or gaining a new one—the cell’s phenotype can change as a result.

What is excision repair?

An enzyme recognizes, binds to, and excises (cuts out) damaged bases or DNA. Then, DNA polymerase fills the gap with complementary DNA and ligase seals the break left by DNA polymerase

What is mismatch repair?

An enzyme recognizes a mismatched base pair, excises it and the surrounding nucleotides, DNA polymerase synthesizes new DNA to fill the gap, DNA ligase seals the break

What are constitutive genes?

Gene products (proteins) that are continuously expressed (ex. central dogma proteins)

What are inducible genes?

Genes that are default off, turned on in response to a substance (ex. digestive enzymes)

What are repressible genes?

Genes that are default on, turned off in response to a substance (ex. amino acids)

What is catabolism? What is anabolism?

Catabolism- processes in which substances are broken down for cell use (typically inducible)

Anabolism- processes in which substances are synthesized for cell use (typically repressible)

What are regulator genes?

Genes that encode proteins that regulate expression of other genes by binding to RPBS (adjacent to promoter)

What are the two types of effector molecules?

Inducers (inducible genes), co-repressors (repressible)

What are the two times dictated by the effector molecule?

Time 1- (default), effector absent (OFF- inducible, ON- repressible)

Time 2- effector present (ON- inducible, OFF- repressible)

What happens during inducible negative control?

Regulatory protein- repressor

Effector molecule- inducer (absent=off, present=on)

Default: repressor is bound to RPBS, transcription is blocked (off)

Regulatory protein unbound→ transcription occurs (on)

What happens during inducible positive control?

Regulatory protein- activator

Effector molecule- inducer (absent=off, present=on)

Default: activator is unbound to RPBS, transcription is blocked (off)

Regulatory protein bound → transcription occurs (on)

What happens during repressible negative control?

Regulatory protein: repressor

Effector molecule: co-repressor (absent=on, present=off)

Default: repressor unbound to RPBS, transcription occurs (on)

Regulatory protein bound → transcription blocked (off)

What happens during repressible positive control?

Regulatory protein: activator

Effector molecule: co-repressor (absent=on, present=off)

Default: activator bound to RPBS, transcription occurs (on)

Regulatory protein bound → transcription occurs (on)

The lac operon is under inducible, negative control with the effector (i.e., inducer) allolactose. The operon only produces the enzymes necessary for lactose catabolism when lactose is present in the environment. When allolactose is present in the environment, how does the inducer interact with the regulatory protein? Is the regulatory protein (i.e., repressor) bound to the promoter? How does this affect transcription?

When allolactose is present in the environment, the effector binds the repressor. The repressor is then no longer bound to the promoter, and transcription occurs (on).

The lac operon is under inducible, negative control with the effector (i.e., inducer) allolactose. The operon only produces the enzymes necessary for lactose catabolism when lactose is present in the environment. When allolactose is absent in the cell’s environment, is the regulatory protein (i.e.,repressor) bound to the promoter? How does this affect transcription of the lactose catabolism pathway?

When allolactose is absent, the repressor is bound to the promoter and blocks transcription of lactase catabolism. Transcription is off.

The lac operon is under inducible, negative control with the effector (i.e., inducer) allolactose. The operon only produces the enzymes necessary for lactose catabolism when lactose is present in the environment. What would happen to the lac operon if the repressor was constantly bound to the promoter, regardless of the presence of allolactose? How do you predict this would affect the bacteria’s long term viability if lactose is rare in the environment?

If the repressor was constantly bound to the promoter due to a mutation, then transcription would be blocked permanently, and lactose could not be utilized by the cell. This would likely not affect the viability of the bacteria if lactose is not present in the environment very often, but it might have a negative effect if lactose becomes present more often.

The lac operon is under inducible, negative control with the effector (i.e., inducer) allolactose. The operon only produces the enzymes necessary for lactose catabolism when lactose is present in the environment. The lac operon is also under inducible, positive control through the action of the cAMP binding protein (CAP). The effector for this regulatory protein is cAMP, a regulatory molecule produced in the absence of glucose. When glucose is present in the environment, and cAMP is low, is the regulatory protein bound or unbound?
How does this affect transcription?

When glucose is present and cAMP levels are low, the regulatory protein (CAP) is unbound, which blocks transcription. This allows the cell to preferentially use glucose over lactose.

What is alternative splicing?

mRNA processing, occurs after transcription, exons are removed from the transcript; mRNA molecules can be spliced in different ways so one transcript is able to produce multiple gene products

What is mRNA stability?

More stable=can be translated more times, less stable=can be translated less; some RNA molecules (siRNA or miRNA) can pair with mRNA to degrade it

What are special transcription factors?

Bind to enhancers, can act close or far from a gene, interact in many different ways

Explain the role of chromatin structure in gene regulation and provide an example of how epigenetic modifications influence gene expression.

Chromatin is a loosely condensed structure made up of DNA and protein. How loose or packed the DNA is determines if RNA polymerase can come in and do transcription. Some DNA is more easily accessible than others, and those genes are transcribed more often. Epigenetic changes describe changes in how DNA is condensed, which can affect offspring. An example of this is if a grandparent experiences famine, the lack of nutrients causes epigenetic changes in the cell, which eventually allow the grandchildren to live longer.

What is epigenetics?

Changes to the structure of chromatin that affect how easily DNA can be transcribed, epigenetic modifications can change within a lifetime and the changes are passed down through generations

What is cancer? What causes cancer at the genetic level?

Cancer is a disease that is characterized by uncontrolled cell proliferation (growth). Somatic mutations that alter the cell cycle and gene regulation cause cancer.

Is cancer one disease or many? Explain

Cancer is a group of many diseases. About 5-10% of cancers are hereditary, while the rest of them are sporadic and come from somatic mutations. In the context of genetics, all cancers come from genetic changes, but not all of these changes are inherited.

What is apoptosis?

Programmed cell death, happens when a cell does not pass a checkpoint during the cell cycle

What are the two types of tumors?

Benign tumors: cells divide more often than normal, can’t invade other tissues (not harmful, can become malignant if more mutations occur)

Malignant tumors: cells divide very rapidly, invade other tissues- metastasize (cancerous)

What are cyclins? What is cyclin M and how does it relate to cancer?

Cyclins: proteins that regulate the cell cycle

Cyclin M: required to begin mitosis; in cancer high levels of cyclin M builds up prematurely which promotes rapid, unchecked cell proliferation

What is the role of tumor suppressor genes and oncogenes in a typical cell, and how do they become dysfunctional in cancer cells (give example)?

Tumor suppressor genes inhibit cell growth if tumor activity is detected. Oncogenes promote cell growth. In cancer, tumor suppressor genes are under expressed and do not inhibit cell growth while oncogenes are overexpressed and promote cancerous cell growth. An example of a tumor suppressor gene is p53 and when it is mutated, it enables damaged DNA to pass through the checkpoints. An example of an oncogene is Myc, which leads to the cancerous growth of B-cells when overexpressed (causes Burkitt Lymphoma).

What are proto-oncogenes?

Positive cell cycle regulators, promote cell growth, when mutated they are overexpressed and promote cancerous cell growth

How does genomic stability relate to cancer?

Genomic stability is the frequency of mutations (less stable=more mutations), lower stability is associated with cancer formation and speeding progression of cancer

How can mutations in P53, BRCA1 + BRCA2, and RAS lead to cancerous cell growth?

P53: p53 is a tumor suppressor protein that normally protects the genome by halting the cell cycle at the G1 checkpoint when DNA damage is detected. A mutation that inactivates p53 prevents it from carrying out this role. Without functional p53, the cell fails to stop at the G1 checkpoint, even when DNA is damaged. As a result, the cell proceeds into S phase and replicates DNA that contains errors. These unrepaired mutations are then passed on to daughter cells during mitosis. This leads to genomic instability

BRCA1/2: BRCA1 and BRCA2 are tumor suppressor genes that help maintain genomic stability by repairing double-
stranded DNA breaks. A mutation prevents proper repair, so DNA damage accumulates instead of being fixed. As unrepaired breaks build up, cells become increasingly genomically unstable, leading to a higher rate of mutations across the genome. This growing mutation load increases the chance that additional key genes involved in cell-cycle control will be affected, which elevates the risk of cancer

RAS: Ras is a proto-oncogene, meaning it normally promotes the cell cycle at the right time. When Ras undergoes a mutation, it becomes an oncogene, which means its activity is increased or unregulated. As a result, Ras promotes cell growth more than it should, even when the cell does not actually need to divide. Because Ras now continually stimulates the cell cycle, the cell begins dividing inappropriately. This uncontrolled proliferation increases the likelihood that additional mutations will occur—especially since rapidly dividing cells have less opportunity to repair DNA damage. Over time, this excessive and unregulated growth contributes to cancer development.

How does treating cancer with precision medicine differ from other types of treatments, such as chemotherapy?

Treating cancer with precision medicine allows doctors to be much more precise and treat cancer on a case-by-case basis. Other cancer treatments like chemotherapy are not very selective, so while they do the job to kill the cancer cells, they also kill normal healthy cells which leads to unpleasant side effects. Precision medicine allows doctors to test different treatments to see which one the tumor responds best to, in order to find the best treatment for each patient.

What are some other mechanisms of cancer? (No miRNA)

Viruses: able to integrate their DNA into the genome, sometimes viral gene products can interact with proteins to promote cancerous growth as oncogenes (ex. HPV)

Epigenetics: modifications in genome can lead to the overexpression of certain proteins which can lead to cancer

What are genetic pathways? What role do genes and their protein products play in genetic pathways?

Genetic pathways are the mechanisms that make up the process of using genes to create phenotypes. One example of a genetic pathway is a regulatory pathway. These pathways involve one gene product controlling the expression or activity by activating or deactivating the next component in the sequence. Mutations in these pathways can disrupt the production of phenotypes controlled by these pathways.

Compare monogenetic and polygenetic traits.

Complex (polygenetic) traits involve several genes controlling a single phenotype. Monogenetic traits involve only one gene controlling a phenotype. Complex traits are more common, especially in complex beings like humans. Complex traits have a lot more phenotypic variation because there are more genes involved in creating the phenotypes, so there are more opportunities to have different genes.

Why would there be redundancy in genetic pathways?

Important genetic pathways are always redundant. Since mutations are random, they are less likely to affect multiple pathways if there are copies present. Function of these genetic pathways can still be maintained, even if only one pathway is still intact.

Using the height distribution graph from lecture, explain why height is considered a polygenic trait. Reference the shape of the distribution in your answer.

The height distribution graph from lecture shows a smooth, bell-shaped curve, indicating that most people fall near an average height and fewer individuals are found at the extremes. This type of continuous variation is characteristic of a polygenic trait, where many genes each contribute a small additive effect to the phenotype. Because height is influenced by thousands of genetic variants, the combined effects of many loci produce a wide range of possible values rather than distinct categories. The normal distribution of heights in the graph reflects this underlying polygenic control.

What was Nilson-Ehle’s experiment? How does it relate to additive genetic variation?

In the Nilson-Ehle experiment, they studied grain color. They hypothesized that grain color was caused by three genes with two alleles, with one allele contributing red pigment. They discovered that more red alleles caused the grains to be more red phenotypically. Additive genetic variation means that if you have more of a specific allele, the more extreme the phenotype will be. This is shown in the experiment because more red alleles caused a more red phenotypic appearance

What does a curve with more genetic variation look like? What does a population with a greater mean look like?

These curves are wider when variation is greater; greater mean shows a curve further to the right

What is the nature vs nurture debate?

The nature vs nurture debate focuses on the idea of what creates phenotypic traits. Nature refers to genetic factors, while nurture refers to environmental factors. The answer to this question is that phenotypic traits are the result of both genetics and environment interact to produce the diverse phenotypes observed in nature.

Explain how a genetically determined trait can have dramatically different phenotypic outcomes depending on environment. Use an example in your answer.

A genetically determined trait can show very different phenotypes when environmental conditions influence how the genotype is expressed. This occurs when the environment modifies developmental pathways, biochemical reactions, or gene regulation. An example is phenylketonuria (PKU). Individuals with PKU have a recessive genetic mutation that prevents them from metabolizing phenylalanine. If they consume a normal diet, toxic byproducts accumulate and cause severe cognitive impairment. However, if the environment is modified—by providing a phenylalanine-restricted diet—the same genotype produces a dramatically different phenotype, and the individual can develop normally. Thus, the genotype is the same, but the phenotype depends strongly on environmental conditions.

What do loss of function and gain of function mutations mean in genetic pathways?

Loss of function=always off, gain of function=always on

Define heritability. How would high environmental variation in phenotype (plasticity) affect heritability estimates (H2) for a trait?

Heritability (H²) is the proportion of total phenotypic variation in a population that is caused by genetic variation among individuals. It is expressed as: H2 = VG/VP = VG/(VG+VE)
If environmental variation is high, then the environmental component of variance (Vₑ) increases. This makes the denominator larger, so heritability decreases. When the environment strongly influences phenotype (high plasticity), genetics explains a smaller fraction of the total variation, leading to lower heritability estimates.

In a changing environment, how would a highly heritable trait be expected to change from one generation to the next? How would a highly plastic trait be expected to change across generations in response to the same environmental changes?

A highly heritable trait depends mostly on genetic differences, so environmental change alone will not immediately shift the phenotype. The trait will only change across generations if natural selection alters allele frequencies. Therefore, phenotypic change is slow and depends on evolutionary processes. A highly plastic trait, however, can change immediately across generations because each generation expresses a phenotype that matches the current environment. Even if genotypes remain the same, a changing environment will produce changing phenotypes.

In a twin study, are identical or fraternal twins expected to have more similar phenotypes? Why is this? How can we use this concept to understand the heritability of phenotypes?

In twin studies, identical twins (monozygotic twins) are expected to have more similarity in their phenotypes than fraternal twins (Dizygotic twins), as identical twins share more genes than fraternal twins. By comparing the similarity of phenotypes in identical vs fraternal twins, which are usually raised in the same environment, traits that are more heritable will be more similar in identical twins than in fraternal twins.

What is complementation?

Mutations in different parts of a pathway have the same net effect

How is a complementation test performed?

Two true breeding mutants are crossed to see what phenotype is produced, used to figure out how many alleles are represented in a single phenotype with pairwise breeding (tables!)

What is quantitative trait loci (QTL) mapping?

Crosses two parents with contrasting phenotypes, compare f2 phenotype with genotype variation to identify QTL- loci associated with variation in a trait (associated QTL identified are likely associated with genes contributing to variation)

What is the goal of QTL mapping and GWAS? Compare and contrast the two types of studies.

QTL mapping and GWAS both aim to identify genetic loci associated with complex traits but differ in approach. QTL mapping uses controlled crosses to pinpoint regions of the genome linked to traits. In contrast, GWAS analyzes genetic variation across entire genomes in large, unrelated populations to find associations between specific genetic loci and traits.

What are Single-Nucleotide Polymorphisms (SNPs)? How can we use SNPs to understand complex traits?

Variation at a single nucleotide position in the DNA sequence among individuals in a population due to a mutation. SNPs often serve as genetic markers because they are common and can be located near genes associated with specific traits. SNPs are used to understand complex traits through studies like Genome-Wide Association Studies (GWAS), which identify correlations between specific SNPs and phenotypic traits. By analyzing these correlations, researchers can pinpoint regions of the genome (i.e., genetic loci) that contribute to the genetic basis of complex traits, such as height, disease susceptibility, or response to medication, and uncover how multiple genes and environmental factors interact to shape these traits.

If a SNP is highly associated with a trait, what does that mean? Why can’t we conclude that this SNP causes the trait?

If a SNP is highly associated with a trait, it means that individuals who carry a particular SNP variant tend to show differences in that trait more often than expected by chance. In other words, the SNP is found near a region that influences the trait, and its allele frequencies correlate with phenotypic differences in the population. We cannot conclude that the SNP causes the trait. The SNP may simply be linked to the gene or mutation because it is located nearby on the chromosome. It could also be in a noncoding region with no functional effect. GWAS identifies correlations, not causation, so additional studies are needed to determine whether the SNP plays a direct biological role.

How similar genetically are humans?

Highly similar; humans share 99% of DNA sequences with the remaining 1% accounting for all differences

What is a gene pool in a population?

Sum total of all alleles for a gene that animals in a population contain, each allele is found at a specific allele frequency in a population

What is a wild type phenotype? What are mutants?

Wild type: most common phenotype in a population

Mutants: all other phenotypes

What is a population?

A group of interbreeding organisms

What is evolution? What is biological evolution?

Evolution: change in allele frequencies in a population over time/across generations

Biological evolution: change in the inherited traits of genotypes of a population from one generation to the next

Evolution acts on populations, not individual organisms. Why is this the case?

Evolution can only act on population gene pools because individual genomes cannot change within an organism’s lifetime. The population gene pool can change over time as certain alleles are passed on more than others, or certain individuals survive more than others.

Explain the migration and mutation mechanisms of evolution

Migration (gene flow): introduces new alleles from other populations, moves variation around

Mutation: introduces new alleles from other populations, ultimate source of genetic variation in DNA

What influences gene flow (migration)?

Geography, distance, and other barriers; these affect likelihood of exchanging genes

What is natural selection?

Individuals with certain alleles are more likely to survive and reproduce compared to the rest of the population

What are the conditions of natural selection?

1. Variation in traits

2. Heritable traits

3. Individuals in population must reproduce

4. Differential fitness (some contribute more genes than others)

What is evolutionary fitness?

The amount of genetic material an individual contributes to the next generation; combination of survival and reproduction; certain allele combinations may promote higher fitness in individuals that have them

What will happen to an allele’s frequency if it provides a fitness advantage? What about a fitness disadvantage?

If the allele provides a fitness advantage, the allele will increase in frequency. If the allele causes a fitness disadvantage, it will decrease in frequency

How does evolution impact human health?

Evolution impacts human health by shaping genetic traits that influence disease susceptibility and resistance. For example, natural selection has led to the presence of genetic variants like the sickle cell allele, which provides protection against malaria but can cause sickle cell disease. Evolution also causes antibiotic resistance in bacteria and influences the basis of complex diseases, such as cancer and diabetes. Understanding these evolutionary processes helps us create treatment options and learn more about genetics.

What is genetic drift?

Changing of allele frequencies by random chance; randomly increased/decreased due to probability (especially in small populations)

What is population bottleneck?

A population is temporarily reduced to a very low number, causing the loss of many alleles (ex. cheetahs)

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