Robbins & Cotran 10th Ed. Pathology Test Bank | Chapter-
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 6-month-old infant presents with failure to thrive and
recurrent infections. Genetic testing shows a point mutation
causing a premature stop codon in an essential immune gene.
Which process most directly explains how this mutation leads
to absent protein product?
A. Nonsense-mediated mRNA decay
B. Frame-shift altering downstream coding sequence
C. Loss of promoter transcription initiation
D. Post-translational ubiquitin-mediated degradation
Answer: A
Rationales — Correct: Nonsense-mediated mRNA decay
recognizes mRNAs with premature stop codons and degrades
,them, preventing translation and resulting in absent protein
product.
Incorrect: B — Frame-shift mutations alter reading frame, not
necessarily create premature stop codon; the question specifies
a point mutation causing a stop.
C — Promoter loss prevents transcription initiation but is not
the direct consequence of a premature stop codon within
coding sequence.
D — Ubiquitin-mediated degradation targets proteins after
translation; here the problem prevents protein accumulation by
degrading the mRNA.
Teaching Point: Premature stop codons often trigger nonsense-
mediated mRNA decay and prevent protein synthesis.
2. Chapter Reference – Chapter 1 — The Genome
Stem: A researcher studies a gene’s expression in liver versus
muscle. She finds the same DNA sequence but markedly
different mRNA levels due to CpG island methylation in liver.
Which mechanism best explains tissue-specific silencing?
A. DNA methylation leading to chromatin condensation and
transcriptional repression
B. Histone acetylation increasing nucleosome destabilization
C. RNA interference triggering mRNA cleavage
D. Alternative splicing removing promoter elements
Answer: A
,Rationales — Correct: DNA methylation of CpG islands recruits
proteins that condense chromatin and repress transcription,
producing tissue-specific gene silencing.
Incorrect: B — Histone acetylation is associated with increased
transcription, not silencing.
C — RNA interference affects mRNA stability post-transcription
and typically requires small RNAs; it does not explain CpG
methylation patterns.
D — Alternative splicing alters mRNA isoforms, not promoter
activity or DNA methylation.
Teaching Point: CpG methylation causes chromatin
condensation and stable transcriptional silencing.
3. Chapter Reference – Chapter 1 — The Genome
Stem: A patient has an inherited mitochondrial disorder. Which
feature distinguishes mitochondrial DNA (mtDNA) inheritance
from nuclear DNA inheritance?
A. Maternal transmission and heteroplasmy leading to variable
penetrance
B. Mendelian autosomal dominant inheritance with full
penetrance
C. X-linked recessive transmission through males only
D. Only paternal transmission during fertilization
Answer: A
, Rationales — Correct: mtDNA is maternally inherited and cells
can contain mixtures of mutant and wild-type mtDNA
(heteroplasmy), producing variable disease severity and
penetrance.
Incorrect: B — mtDNA disorders do not follow Mendelian
autosomal patterns.
C — X-linkage is a nuclear chromosome phenomenon, not
mtDNA.
D — Paternal mitochondria are typically not transmitted to
offspring.
Teaching Point: Mitochondrial diseases show maternal
inheritance and heteroplasmy with variable expression.
4. Chapter Reference – Chapter 1 — The Genome
Stem: A tumor shows loss of heterozygosity (LOH) at a locus
containing a tumor suppressor gene. Which mutational
sequence fits the "two-hit" model for tumor suppressor
inactivation?
A. Germline allele mutated; somatic deletion of the remaining
wild-type allele
B. Two independent activating point mutations in the same
oncogene
C. One allele hypermethylated; the other overexpressed
D. Increased copy number (amplification) of the tumor
suppressor gene
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1. Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 6-month-old infant presents with failure to thrive and
recurrent infections. Genetic testing shows a point mutation
causing a premature stop codon in an essential immune gene.
Which process most directly explains how this mutation leads
to absent protein product?
A. Nonsense-mediated mRNA decay
B. Frame-shift altering downstream coding sequence
C. Loss of promoter transcription initiation
D. Post-translational ubiquitin-mediated degradation
Answer: A
Rationales — Correct: Nonsense-mediated mRNA decay
recognizes mRNAs with premature stop codons and degrades
,them, preventing translation and resulting in absent protein
product.
Incorrect: B — Frame-shift mutations alter reading frame, not
necessarily create premature stop codon; the question specifies
a point mutation causing a stop.
C — Promoter loss prevents transcription initiation but is not
the direct consequence of a premature stop codon within
coding sequence.
D — Ubiquitin-mediated degradation targets proteins after
translation; here the problem prevents protein accumulation by
degrading the mRNA.
Teaching Point: Premature stop codons often trigger nonsense-
mediated mRNA decay and prevent protein synthesis.
2. Chapter Reference – Chapter 1 — The Genome
Stem: A researcher studies a gene’s expression in liver versus
muscle. She finds the same DNA sequence but markedly
different mRNA levels due to CpG island methylation in liver.
Which mechanism best explains tissue-specific silencing?
A. DNA methylation leading to chromatin condensation and
transcriptional repression
B. Histone acetylation increasing nucleosome destabilization
C. RNA interference triggering mRNA cleavage
D. Alternative splicing removing promoter elements
Answer: A
,Rationales — Correct: DNA methylation of CpG islands recruits
proteins that condense chromatin and repress transcription,
producing tissue-specific gene silencing.
Incorrect: B — Histone acetylation is associated with increased
transcription, not silencing.
C — RNA interference affects mRNA stability post-transcription
and typically requires small RNAs; it does not explain CpG
methylation patterns.
D — Alternative splicing alters mRNA isoforms, not promoter
activity or DNA methylation.
Teaching Point: CpG methylation causes chromatin
condensation and stable transcriptional silencing.
3. Chapter Reference – Chapter 1 — The Genome
Stem: A patient has an inherited mitochondrial disorder. Which
feature distinguishes mitochondrial DNA (mtDNA) inheritance
from nuclear DNA inheritance?
A. Maternal transmission and heteroplasmy leading to variable
penetrance
B. Mendelian autosomal dominant inheritance with full
penetrance
C. X-linked recessive transmission through males only
D. Only paternal transmission during fertilization
Answer: A
, Rationales — Correct: mtDNA is maternally inherited and cells
can contain mixtures of mutant and wild-type mtDNA
(heteroplasmy), producing variable disease severity and
penetrance.
Incorrect: B — mtDNA disorders do not follow Mendelian
autosomal patterns.
C — X-linkage is a nuclear chromosome phenomenon, not
mtDNA.
D — Paternal mitochondria are typically not transmitted to
offspring.
Teaching Point: Mitochondrial diseases show maternal
inheritance and heteroplasmy with variable expression.
4. Chapter Reference – Chapter 1 — The Genome
Stem: A tumor shows loss of heterozygosity (LOH) at a locus
containing a tumor suppressor gene. Which mutational
sequence fits the "two-hit" model for tumor suppressor
inactivation?
A. Germline allele mutated; somatic deletion of the remaining
wild-type allele
B. Two independent activating point mutations in the same
oncogene
C. One allele hypermethylated; the other overexpressed
D. Increased copy number (amplification) of the tumor
suppressor gene
