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A patient undergoes genomic tumour

profiling, which reveals complete loss of function of a key tumour suppressor

gene. The report notes that a single inherited pathogenic allele was present in

all normal tissue, whilst the second allele was functional. However, in the

tumour, the second allele was lost through a somatic deletion.

Based on this information, which

statement BEST explains the role of tumour suppressor genes (TSGs) in cancer

development?

Loss

of both functional TSG alleles is typically required to drive tumour formation

TSGs are normally

inactive and become switched on only during tumour formation

TSGs prevent proto‑

oncogenes

from converting into oncogenes

TSGs function solely

by regulating cell

‑cycle checkpoints

A pharmaceutical company is developing

a targeted therapy for non-small cell lung cancer (NSCLC). They observe that

some tumours have overactive signalling through the EGFR, which drives

uncontrolled cell proliferation, even in the absence of its ligand.

Which statement best explains the

mechanism behind this hyperactive EGFR signalling in cancer?

EGFR acts as a

transcription factor to directly activate cell survival genes

Both EGFR alleles are

commonly lost in lung cancer, leading to loss of growth signalling

Inherited EGFR

mutations directly cause retinoblastoma in affected individuals

Mutations

in the EGFR kinase domain cause the receptor to signal independently of ligand

binding, promoting uncontrolled proliferation

What does the graph below indicate about the success of IVF cycles?

There appears to be benefit in undertaking three IVF cycle in an attempt to conceive up to the age of ~41

There is limited benefit in undertaking multiple IVF cycles

The chance of conceiving by IVF appears to begin to decline after age 38

People under the age of 30 have the best chance of conceiving by IVF

What does the graph below indicate about nephron number and birth weight?

A lower birthweight is correlated with a higher number of nephrons within the kidney

An individual with a lower birth weight will always have a larger number of nephrons in their kidney than someone with a higher birth weight

An individual with a higher birth weight will always have a larger number of nephrons in their kidney than someone with a lower birth weight

A higher birthweight is correlated with a higher number of nephrons within the kidney

In the graph above P = protein, C = carbohydrates and F = fat. This data comes from a study on rats that were subjected to fetal growth restriction.

Pregnant mice were fed one of the two diets, indicated in the diagram above, and the nephron number in the kidneys of their offspring was determined. What can we conclude about the impact of the maternal diet on the nephron number of the rat offspring?

The maternal diet does not have a significant impact on the number of nephrons in the kidneys of the developing offspring

An increase in the amount of fat in the diets of the offspring partially recues the issues caused by fetal growth restriction, as shown by an increased number of nephrons in their kidneys

An increase in the amount of fat in the maternal diet increases the number of nephrons in their developing offspring

The impact of fetal growth restriction can be completely rescued by switching the maternal diet to a high fat diet

In the graph below each symbol represents a distinct district or borough. What does the data in the figure above indicate?

Individuals subjected to a suboptimal fetal environment are more likely to develop coronary heart disease

Individuals subjected to a suboptimal fetal environment will develop coronary heart disease

Individuals with an ideal fetal environment are very unlike to develop coronary heart disease

Individuals subjected to a suboptimal fetal environment are less likely to develop coronary heart disease

Ultraviolet (UV) radiation can cause

cyclobutane pyrimidine dimers (CPDs) and 6,4 photoproducts, which distort the

DNA helix. Cells must remove these lesions to restore normal DNA structure

before replication occurs.

Which sequence of events best explains

how cells repair this type of DNA damage?

The damaged DNA bases

are directly converted into normal bases using DNA polymerase

The damaged DNA

strand is degraded and replaced with an entirely new DNA strand

The

damaged DNA is recognised and cleaved by a repair complex, before the damaged

segment is removed and the gap is filled

DNA polymerase

directly replaces the damaged bases without removing the surrounding DNA

sequence

Researchers experimentally delete both

copies of the RB transcriptional corepressor 1 (RB1) gene in cultured human

cells. They observe that the cells begin progressing through the G1/S

checkpoint without proper control, leading to uncontrolled proliferation.

Which conclusion best explains this

observation?

RB1 functions

primarily as a transcription factor that directly drives cell proliferation,

promoting cancer development

RB1 normally

activates DNA replication, so its loss blocks cell division

Loss

of both RB1 alleles removes an important cell-cycle brake, promoting cancer

development

Activation of a

single RB1 allele is sufficient to cause tumorigenesis

to introduce a precise
double-strand break

A researcher plans to use

zinc finger

nucleases (ZFNs)

at a specific site in a gene for genome editing.

They know that ZFNs rely on

DNA-binding
domains fused to the FokI nuclease

, which only cleaves DNA when

properly dimerized.

Which strategy best explains how ZFNs achieve site-specific DNA cleavage?

single ZFN protein with one FokI monomer binds the DNA and cleaves it on its

own

directly to same region of the target cleavage
sites
, allowing the FokI nucleases to dimerize and cut the DNA

Two

separate ZFN proteins are designed to bind

Two

separate ZFN proteins are designed to bind

opposite sides of the target site

allowing the FokI nucleases to dimerize and cut the DNA

single ZFN protein binds the target site and recruits a pre-formed FokI dimer

to cleave the DNA