VCE-BIO-U34 10.1 📋 – Practice Exam 7: Question Paper

Epigenetics is best defined as the study of:

In mammals, DNA methylation predominantly occurs on cytosine bases that are:

DNA methyltransferase (DNMT) enzymes function by:

Increased methylation of a gene’s promoter region typically results in:

Acetylation of histone tails by histone acetyltransferases (HATs) generally:

Histone deacetylase (HDAC) enzymes act to:

Compared with euchromatin, heterochromatin is:

ATP-dependent chromatin remodelling complexes regulate gene expression by:

The ‘histone code’ hypothesis proposes that:

In the agouti viable yellow (Avy) mouse model, coat colour variation among genetically identical littermates arises because:

When pregnant agouti mice are fed a diet supplemented with methyl donors such as folate, vitamin B12 and choline, the offspring show:

Maternal exposure to the endocrine-disrupting chemical bisphenol A (BPA) in agouti mice tends to:

Studies of individuals prenatally exposed to the Dutch Hunger Winter (1944-45) famine found that, decades later, these individuals showed:

Transgenerational epigenetic inheritance refers to:

Genomic imprinting is an epigenetic phenomenon in which:

Prader-Willi syndrome typically results from:

Angelman syndrome arises when:

In female mammals, random X-chromosome inactivation results in:

The long non-coding RNA Xist contributes to X-inactivation by:

Studies of monozygotic (identical) twins, such as Fraga et al. (2005), found that:

Monozygotic twin studies are valuable for epigenetic research primarily because:

In many cancers, tumour suppressor genes (e.g. BRCA1, p16/CDKN2A) are frequently inactivated by:

Global hypomethylation of the genome, commonly observed in cancer cells, is associated with:

Azacitidine, used clinically to treat certain cancers such as myelodysplastic syndrome, works by:

Histone deacetylase (HDAC) inhibitors are being explored as cancer treatments because they:

The Horvath epigenetic clock estimates an individual’s biological age by:

When an individual’s epigenetic (biological) age, as measured by an epigenetic clock, is significantly higher than their chronological age, this is generally associated with:

MicroRNAs (miRNAs) regulate gene expression epigenetically by:

Compared with miRNAs, small interfering RNAs (siRNAs) typically:

During mammalian gametogenesis and early embryogenesis, most epigenetic marks are:

Imprinted genes are able to maintain parent-of-origin-specific expression through epigenetic reprogramming because:

Bisulfite sequencing is a laboratory technique used to detect DNA methylation because it:

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is used to:

In studies of maternal care in rats (Meaney and colleagues), offspring of mothers displaying low licking/grooming behaviour showed:

The mottled or mosaic coat pattern seen in some agouti mice reflects:

One key molecular mechanism by which promoter methylation silences gene expression is that methylated cytosines:

CpG islands, which are regions of DNA with a high frequency of CG dinucleotides, are most commonly found:

Histone methylation can either activate or repress transcription depending on the specific residue modified; for example:

Polycomb repressive complexes contribute to epigenetic gene silencing during development by:

The gradual, stochastic accumulation of epigenetic changes across an individual’s lifetime, contributing to increasing epigenetic divergence between monozygotic twins and to age-related disease risk, is known as:

Question 1: DNA Methylation Mechanism

Question 1: DNA Methylation Mechanism
DNA methylation is a key epigenetic mechanism used to regulate gene expression in eukaryotic cells.
(i) Describe the chemical process of DNA methylation, including the enzyme involved and the base modified. (2 marks)
(ii) Explain how this modification can result in the silencing of gene expression, referring to transcription factor binding and chromatin structure. (3 marks)

Question 2: Histone Modification and Chromatin Structure

Question 2: Histone Modification and Chromatin Structure (a)
Distinguish between euchromatin and heterochromatin in terms of structure, histone modification state and transcriptional activity.

Question 2: Histone Modification and Chromatin Structure

Question 2: Histone Modification and Chromatin Structure (b)
Explain, using the histone code hypothesis, how a combination of different histone modifications can determine whether a gene is expressed.

Question 2: Histone Modification and Chromatin Structure

Question 2: Histone Modification and Chromatin Structure (c)
A researcher treats cancer cells with an HDAC inhibitor. Predict and explain the effect this treatment would have on chromatin structure and the expression of previously silenced tumour suppressor genes.

Question 3: Agouti Mouse Case Study

Question 3: Agouti Mouse Case Study (a)
The agouti viable yellow (Avy) mouse is a well-studied model of epigenetic gene regulation. Genetically identical Avy mice display a range of coat colours from yellow through mottled to brown (pseudoagouti), which correlates with the degree of methylation of a retrotransposon (intracisternal A particle, IAP) inserted upstream of the Agouti gene. In one experiment, female mice were fed either a control diet or a diet supplemented with methyl donors (folate, vitamin B12, choline, betaine) prior to and during pregnancy. The table below summarises offspring coat colour distribution.

Diet | % Yellow | % Mottled | % Brown (pseudoagouti)
Control | 40% | 35% | 25%
Methyl-supplemented | 15% | 30% | 55%

Explain why offspring in this experiment are genetically identical but show a range of coat colours.

Question 3: Agouti Mouse Case Study

Question 3: Agouti Mouse Case Study (b)
Using the data in the table, describe the effect of maternal methyl-donor supplementation on offspring coat colour, and explain the molecular basis for this effect.

Question 3: Agouti Mouse Case Study

Question 3: Agouti Mouse Case Study (c)
A separate cohort of pregnant mice was exposed to BPA. Predict the effect this would have on the coat colour distribution of offspring compared with the control diet, and justify your prediction.

Question 3: Agouti Mouse Case Study

Question 3: Agouti Mouse Case Study (d)
Explain why this mouse model is considered strong evidence for epigenetic (rather than genetic) inheritance of a phenotype.

Question 4: Dutch Hunger Winter

Question 4: Dutch Hunger Winter (a)
The Dutch Hunger Winter (1944-45) occurred when a German blockade caused severe famine in parts of the Netherlands. Children conceived during this famine were later found, in adulthood, to have significantly different DNA methylation patterns at the IGF2 gene compared with their unexposed same-sex siblings, as well as increased rates of obesity, cardiovascular disease and type 2 diabetes. Explain why comparing prenatally-exposed individuals with their unexposed siblings, rather than with unrelated individuals, strengthens the conclusion that the observed differences are due to epigenetic changes rather than genetic differences.

Question 4: Dutch Hunger Winter

Question 4: Dutch Hunger Winter (b)
Outline the concept of a ‘critical window’ of epigenetic susceptibility during development, and explain why prenatal exposure (rather than exposure later in life) had such a significant lasting effect.

Question 5: Twin Study of Epigenetic Divergence

Question 5: Twin Study of Epigenetic Divergence (a)
Fraga et al. (2005) studied pairs of monozygotic twins of varying ages and lifestyles, measuring global DNA methylation and histone acetylation levels in their cells. They found that younger twin pairs (and those with similar lifestyles who had spent more of their lives together) showed very similar epigenetic profiles, while older twin pairs (and those with more divergent lifestyles, e.g. differing smoking status, diet or exercise habits, who had spent less time living together) showed substantially different epigenetic profiles. Explain why monozygotic twins provide an ideal model for distinguishing the effects of environment from genotype on gene expression.

Question 5: Twin Study of Epigenetic Divergence

Question 5: Twin Study of Epigenetic Divergence (b)
Explain, with reference to environmental factors, why older twin pairs showed greater epigenetic divergence than younger twin pairs.

Question 5: Twin Study of Epigenetic Divergence

Question 5: Twin Study of Epigenetic Divergence (c)
A pair of monozygotic twins is discordant for a particular autoimmune disease (one twin is affected, the other is not). Using your understanding of epigenetics, explain how this could occur despite the twins having identical DNA sequences.

Question 6: Epigenetics in Cancer

Question 6: Epigenetics in Cancer (a)
Many cancers show characteristic epigenetic changes, including hypermethylation of specific tumour suppressor gene promoters (e.g. BRCA1, p16) alongside global hypomethylation of the rest of the genome. Explain how promoter hypermethylation of a tumour suppressor gene such as p16 could contribute to uncontrolled cell proliferation.

Question 6: Epigenetics in Cancer

Question 6: Epigenetics in Cancer (b)
A new class of anti-cancer drugs combines a DNA methyltransferase inhibitor with a histone deacetylase inhibitor. Explain why this combination might be more effective at reactivating silenced tumour suppressor genes than either drug alone.

Question 7: Genomic Imprinting

Question 7: Genomic Imprinting (a)
The chromosome 15q11-13 region contains genes subject to genomic imprinting. Genes in this region are expressed only from the paternal chromosome in some cases (e.g. genes deleted in Prader-Willi syndrome) and only from the maternal chromosome in others (e.g. UBE3A, deleted/silenced in Angelman syndrome). Explain what is meant by ‘genomic imprinting’ and describe how imprinting is established during gametogenesis.

Question 7: Genomic Imprinting

Question 7: Genomic Imprinting (b)
A child inherits a deletion of the 15q11-13 region on the chromosome received from their father. Using your knowledge of imprinting, explain why this child develops Prader-Willi syndrome rather than Angelman syndrome.

Question 7: Genomic Imprinting

Question 7: Genomic Imprinting (c)
Explain why genomic imprinting is considered an epigenetic, rather than genetic, phenomenon.

Question 8: The Epigenetic Clock

Question 8: The Epigenetic Clock (a)
The Horvath epigenetic clock estimates ‘biological age’ from DNA methylation levels at approximately 350 specific CpG sites across the genome. Researchers measured epigenetic age in two 50-year-old men, A and B. Person A had a smoking history of 30 years and a sedentary lifestyle; his epigenetic age was estimated at 58 years. Person B had never smoked and exercised regularly; his epigenetic age was estimated at 46 years. Using the data provided, explain what is meant by ‘epigenetic age acceleration’ and interpret the results for Person A and Person B.

Question 8: The Epigenetic Clock

Question 8: The Epigenetic Clock (b)
Explain, in terms of underlying molecular mechanisms, how lifestyle factors such as smoking could lead to accelerated epigenetic ageing.

Question 9: X-Inactivation

Question 9: X-Inactivation (a)
Explain the process of random X-chromosome inactivation in female mammals, including the role of the Xist gene and the formation of the Barr body.

Question 9: X-Inactivation

Question 9: X-Inactivation (b)
Female mammals heterozygous for an X-linked gene (e.g. for coat colour, as in calico cats) often display a mosaic/patchy phenotype. Explain why this occurs, using your understanding of X-inactivation.

Question 10: Non-Coding RNA and Gene Silencing

Question 10: Non-Coding RNA and Gene Silencing (a)
Compare the mechanisms of gene silencing used by microRNA (miRNA) and small interfering RNA (siRNA), and explain how each contributes to the regulation of gene expression.

Question 10: Non-Coding RNA and Gene Silencing

Question 10: Non-Coding RNA and Gene Silencing (b)
A researcher wants to experimentally ‘knock down’ expression of a specific gene in cultured human cells to study its function. Explain how synthetic siRNA could be used to achieve this, and outline one limitation of this approach.