Genetics Exam II

What is the Kozak Sequence?

A conserved nucleotide sequence surrounding the start codon in eukaryotic mRNA that helps the ribosome recognize the correct start site for translation.

What is an Exon?

A coding segment of a gene that remains in the mature mRNA, containing the information used to make protein.

What are base analogs?

Chemicals that resemble normal DNA bases and can be incorporated during replication.

What are alkylating agents?

Chemicals that add alkyl groups to DNA bases, causing mispairing and point mutations.

What are intercalating agents?

Molecules that insert between DNA bases, causing insertions or deletions during replication.

What are deaminating agents?

Chemicals that remove amino groups from bases, leading to base-pair changes.

Why are PFAS associated with cancer risk despite not being mutagenic in the Ames test?

PFAS act through biological mechanisms that promote carcinogenesis without directly causing DNA mutations detectable by the Ames test.

How do viruses cause cancer?

By altering cellular processes, carrying oncogenes, integrating DNA into the host genome, and causing chronic inflammation.

Where are bisphenols commonly found?

In plastic containers, water bottles, food can linings, and thermal paper receipts.

Where are phthalates commonly found?

In personal care products, vinyl flooring, shower curtains, and plastic toys.

Where are PFAS commonly found?

In nonstick cookware, water-resistant clothing, stain-resistant carpets, and firefighting foams.

What is the normal role of RAS genes in the cell?

To act as molecular switches controlling growth, division, and survival in response to external signals.

What processes does p53 regulate?

Cell cycle arrest, DNA repair, apoptosis, senescence, and metabolism/oxidative stress response.

Where are most mutations in the p53 gene found in active cancer?

In the DNA-binding domain, which is critical for p53's regulatory functions.

How does p53 regulate genes responsible for DNA repair?

p53 is stabilized and activated in response to DNA damage, allowing it to bind to target genes.

How can p53 selectively activate specific genes?

By binding to specific DNA sequences and relying on cofactors and chromatin structure.

What processes promoted by inflammation can contribute to cancer?

Increased cell proliferation, genomic instability, and angiogenesis.

What are three environmental agents associated with inflammation and cancer?

Tobacco smoke, ultraviolet (UV) radiation, and certain infectious agents.

What are gene fusions?

Gene fusions are hybrid genes formed when segments of two different genes become abnormally joined, creating a single chimeric gene that can produce an altered or misregulated protein.

How are gene fusions formed?

Gene fusions are typically formed through chromosomal rearrangements such as translocations, inversions, deletions, or duplications that occur when DNA breaks and is improperly repaired.

What molecular tools can detect gene fusions?

Detection of gene fusions can be accomplished using karyotyping, fluorescence in situ hybridization (FISH), reverse transcription PCR (RT-PCR), and next-generation sequencing (NGS).

Can gene fusions function as cancer drivers?

Yes, there is strong evidence that gene fusions can act as cancer drivers by producing proteins that promote uncontrolled cell growth or survival.

What is an example of a gene fusion that acts as a cancer driver?

The BCR-ABL fusion, created by the Philadelphia chromosome, generates a constitutively active tyrosine kinase that drives chronic myelogenous leukemia.

What is another example of a gene fusion in cancer?

The TMPRSS2-ERG fusion in prostate cancer leads to abnormal expression of a transcription factor that promotes tumor development.

What is Sustained Proliferative Signaling in cancer?

It refers to cancer cells' ability to continuously divide themselves, bypassing normal growth controls.

How can mutations in the RAS gene affect cancer?

A mutation in the RAS gene can produce a constantly active RAS protein, driving uncontrolled cell division.

What does Evading Growth Suppressors mean in cancer?

It means cancer cells ignore signals from proteins that inhibit cell division.

How can mutations in TP53 affect cancer cells?

Mutations in TP53 can inactivate the p53 protein, preventing cell cycle arrest in response to DNA damage.

What is Resisting Cell Death (Apoptosis) in cancer?

It refers to cancer cells avoiding programmed cell death that would normally eliminate damaged cells.

How does overexpression of BCL-2 affect cancer?

Overexpression of BCL-2 can block apoptosis, allowing damaged cells to survive and proliferate.

What is Enabling Replicative Immortality in cancer?

It refers to cancer cells' ability to divide indefinitely by maintaining their telomeres.

How do mutations that activate TERT affect cancer cells?

Mutations that activate TERT maintain telomere length, preventing normal cellular aging.

What is Inducing Angiogenesis in cancer?

It is the process by which tumors stimulate the growth of new blood vessels to supply nutrients and oxygen.

How does overexpression of VEGF contribute to cancer?

Overexpression of VEGF drives angiogenesis, supporting tumor growth.

What does Activating Invasion and Metastasis mean in cancer?

It refers to cancer cells gaining the ability to invade surrounding tissues and spread to distant sites.

How can mutations in CDH1 affect cancer progression?

Mutations in CDH1 can disrupt cell-cell adhesion, facilitating invasion and metastasis.

What was the original purpose of Robert Nerem's study?

To investigate how a high-fat diet affected heart health and atherosclerosis in rabbits.

Why were rabbits chosen for the study by Robert Nerem?

Rabbits develop elevated cholesterol and artery fatty deposits in response to high-fat feeding, resembling human cardiovascular disease.

What surprising findings came from Robert Nerem's study?

Some rabbits fed a high-fat diet had healthier blood vessels than expected, influenced by gentle handling and socialization.

Why did the editors of Science likely publish Robert Nerem's study?

It highlighted the significant influence of social and environmental conditions on physiological disease outcomes.

What is the definition of epigenetic?

Epigenetic refers to heritable changes in gene expression or cellular phenotype that occur without altering the underlying DNA sequence.

What can cause epigenetic changes?

Epigenetic changes can be caused by chemical modifications to DNA or histone proteins, influenced by environmental factors.

What are examples of epigenetic effects in humans?

Examples include the Dutch Hunger Winter and the Montreal Ice Storm, which led to lasting epigenetic marks affecting health outcomes.

What were the effects of the Dutch Hunger Winter on children?

Children born during the Dutch Hunger Winter had higher risks of obesity, diabetes, and cardiovascular disease linked to altered DNA methylation.

What were the effects of the Montreal Ice Storm on children?

Children exposed to stress during the Montreal Ice Storm exhibited epigenetic changes in stress-response genes associated with cognitive and behavioral outcomes.

What is precision medicine in cancer?

Precision medicine in cancer aims to tailor treatment to an individual's specific tumor characteristics using genetic information.

What does whole genome sequencing (WGS) provide?

WGS provides a comprehensive view of all DNA in a patient's cells, including mutations in protein-coding genes and non-coding regions.

What information does RNA sequencing (RNA-seq) provide?

RNA-seq analyzes the transcriptome, revealing gene expression levels, alternative splicing events, and fusion transcripts.

What is tumor heterogeneity?

Tumor heterogeneity refers to genetic, epigenetic, and phenotypic differences among cancer cells within the same tumor.

How was tumor heterogeneity discovered?

It was discovered through studies sequencing multiple regions of the same tumor, revealing different mutations in different areas.

What are the implications of tumor heterogeneity on cancer prognosis?

It can make tumors more aggressive, harder to treat, and more likely to develop resistance to therapies.

How does exposure to high levels of air pollution increase lung cancer risk?

It increases risk through DNA damage from pollutants and chronic inflammation that promotes tumor development.

What are four common types of mutations during DNA replication?

Base substitutions, insertions, deletions, and slippage errors.

Are replication errors significant for DNA integrity?

Yes, they can accumulate over time and contribute to cancer, aging, or genetic diseases.

How do cells correct replication errors?

Cells use mismatch repair, base excision repair, nucleotide excision repair, and double-strand break repair.

Name four types of chemical or environmental mutagens.

Polycyclic aromatic hydrocarbons (PAHs), ultraviolet (UV) radiation, alkylating agents, and ionizing radiation.

What is radon and why is it significant in Ohio?

Radon is a radioactive gas from uranium decay that accumulates in homes, increasing lung cancer risk.

Give an example of an important gene fusion event that promotes cancer.

The BCR-ABL fusion in chronic myeloid leukemia (CML) is a well-known example.

Are gene fusion events important in studying cancer biology?

Yes, they are important drivers in many cancers and critical for understanding cancer biology.

Are PFAS and bisphenols mutagens?

They are generally not classical mutagens; they act as endocrine disruptors or epigenetic modifiers.

What is the significance of DNA repair in cells?

DNA repair is essential for maintaining genetic stability and preventing harmful outcomes like cell death or diseases such as cancer.

What are three mechanisms that regulate gene expression at the DNA level?

1. DNA methylation, which represses gene expression by preventing transcription factor binding. 2. Histone modification, which alters DNA accessibility for transcription. 3. Chromatin remodeling, which influences the active or inactive state of genes.

What is a core promoter?

A short DNA region near the start of a gene where the transcription machinery assembles, determining where transcription begins.

What is the 5' Start Site?

The exact nucleotide where RNA polymerase begins RNA synthesis, defining the beginning of the RNA transcript.

What controls the position of the 5' Start Site?

Promoter sequences and transcription factor binding guide RNA polymerase to the correct initiation point.

What is the 5' UTR?

The segment of mRNA upstream of the coding sequence that regulates translation efficiency and mRNA stability.

What is the Start Site (start codon)?

Usually AUG, it is where translation into protein begins and sets the reading frame for protein synthesis.

What are GT & AG sequences?

Conserved sequences at intron boundaries critical for signaling where splicing should occur.

What are Splicing Consensus Sequences?

Short conserved DNA/RNA sequences at exon-intron junctions that ensure introns are correctly removed and exons joined.

What is an Intron?

A noncoding segment removed from pre-mRNA during splicing, allowing regulation and alternative splicing.

What is an Open Reading Frame (ORF)?

A continuous stretch of codons from start to stop codon that defines the portion of mRNA that encodes a protein.

What is a Stop Site (stop codon)?

A codon that signals the end of translation, ensuring proteins are made to the correct length.

What is the 3' UTR?

The region of mRNA downstream of the stop codon that regulates mRNA stability, localization, and translation efficiency.

What is the 3' Cleavage Site?

The location where pre-mRNA is cut before the addition of the poly (A) tail, important for proper mRNA processing.

What is a miRNA Binding Site?

Typically located in the 3' UTR, where microRNAs bind to repress translation or promote mRNA degradation.

What are Enhancers?

DNA elements that increase transcription by providing binding sites for regulatory proteins, located upstream, downstream, or far from the gene.

What are the consequences of mutations in protein coding regions?

They can change the amino acid sequence of a protein, potentially leading to nonfunctional proteins or diseases.

What are the consequences of mutations elsewhere in the genome?

They typically affect how, when, and how much a gene is expressed, which can have significant biological effects.

Where do most mutations occur in the genome?

Most mutations occur in noncoding regions, which make up the majority of DNA and often have little immediate effect.

What is the Ames test?

A test used to determine whether a chemical is a mutagen by assessing its ability to cause DNA mutations in bacteria.

What are Copy Number Variants (CNVs)?

Segments of DNA that are duplicated or deleted, leading to different numbers of copies of those sequences among individuals.

Why are some CNVs linked to disease?

Having too many or too few copies of certain genes can disrupt normal gene expression and interfere with biological pathways.

What are four examples of spontaneous or replication error mutations?

1. Base substitutions. 2. Insertions. 3. Deletions. 4. Frameshift mutations.

How significant are spontaneous or replication error mutations as a source of mutation?

They are generally less important compared to spontaneous chemical changes and environmental damage, as DNA polymerase has proofreading abilities.

What are four different types of chemical mutagens?

1. Alkylating agents. 2. Base analogs. 3. Intercalating agents. 4. Radiation.

What is the principle of RT-PCR using SYBR Green II?

RT-PCR using SYBR Green II involves amplifying RNA to quantify gene expression levels.

What does RT-PCR stand for?

Reverse Transcriptase PCR

What is the purpose of RT-PCR?

To quantify RNA by converting it to complementary DNA (cDNA) and amplifying specific sequences in real-time.

What components are needed for RT-PCR?

RNA template, reverse transcriptase, DNA polymerase, primers, nucleotides, buffer, and SYBR Green dye.

Why must RNA be converted to cDNA in RT-PCR?

DNA polymerase cannot amplify RNA directly.

What is the principle of visualization using SYBR Green?

SYBR Green binds double-stranded DNA, emitting fluorescence proportional to the amount of DNA generated.

What are the phases of PCR cycles?

Lag phase, linear/exponential phase, plateau phase.

What is a housekeeping gene?

A gene that is consistently expressed in all cell types and essential for basic cellular functions.

Why was real-time PCR used to monitor COVID-19 in sewage?

To detect viral RNA fragments in wastewater for early warning of infection trends.

What did the ENCODE project reveal about the human genome?

It showed that the human genome is more complex than previously believed, with about 80% having functional roles.

What is the Ames test used for?

To screen chemicals for their ability to cause DNA mutations.

What is tautomeric shift in DNA?

A temporary change in DNA bases that alters their pairing properties, leading to incorrect base pairing during replication.

What is depurination?

The loss of a purine base from the DNA strand, leading to gaps that may be filled incorrectly during replication.

What is deamination in DNA?

The removal of an amino group from a base, such as converting cytosine to uracil.

What is the Philadelphia chromosome?

A chromosomal abnormality associated with chronic myelogenous leukemia (CML) formed by a translocation between chromosomes 9 and 22.