A 12-hour old male infant is seen in the newborn nursery. He was born full term by vaginal delivery to a 40-year-old G4P3-->4 mother. Her pregnancy and delivery were uncomplicated, notable only for declining genetic testing. On exam, her son has a flat face, a fold in the upper eyelid, palpebral fissures that appear to slant upwards, and small ears. The diagnostic test for her son’s most likely condition should be conducted during which of the following phases of the cell cycle?
Q92
A 7-year-old girl presents to her primary care physician for a routine check-up. The physician allows the medical student to perform a physical examination. The medical student notes hearing impairment as well as the findings show in Figures A and B. Radiographs show indications of multiple old fractures of the humerus that have healed. After questioning the girl’s parents, the medical student learns that in addition, the patient is extremely picky with her food and eats a diet consisting mainly of cereal and pasta. What is the most likely etiology of the patient’s disease?
Q93
An investigator is studying human genetics and cell division. A molecule is used to inhibit the exchange of genetic material between homologous chromosomes. Which of the following phases of the cell cycle does the molecule target?
Q94
A 2-month-old boy is brought to the physician by his mother because of poor weight gain and irritability since delivery. He is at the 10th percentile for height and below the 5th percentile for weight. Physical examination shows conjunctival pallor. Laboratory studies show:
Hemoglobin 11.2 g/dL
Mean corpuscular hemoglobin 24.2 pg/cell
Mean corpuscular volume 108 μm3
Serum
Ammonia 26 μmol/L (N=11–35 μmol/L)
A peripheral blood smear shows macrocytosis of erythrocytes and hypersegmented neutrophils. Supplementation with folate and cobalamin is begun. Two months later, his hemoglobin concentration is 11.1 g/dL and mean corpuscular volume is 107 μm3. The patient's condition is most likely caused by failure of which of the following enzymatic reactions?
Q95
Red-green color blindness, an X-linked recessive disorder, has an incidence of 1/200 in males in a certain population. What is the probability of a phenotypically normal male and female having a child with red-green color blindness?
Q96
A 9-month-old female is brought to the emergency department after experiencing a seizure. She was born at home and was normal at birth according to her parents. Since then, they have noticed that she does not appear to be achieving developmental milestones as quickly as her siblings, and often appears lethargic. Physical exam reveals microcephaly, very light pigmentation (as compared to her family), and a "musty" body odor. The varied manifestations of this disease can most likely be attributed to which of the following genetic principles?
Molecular Genetics US Medical PG Practice Questions and MCQs
Question 91: A 12-hour old male infant is seen in the newborn nursery. He was born full term by vaginal delivery to a 40-year-old G4P3-->4 mother. Her pregnancy and delivery were uncomplicated, notable only for declining genetic testing. On exam, her son has a flat face, a fold in the upper eyelid, palpebral fissures that appear to slant upwards, and small ears. The diagnostic test for her son’s most likely condition should be conducted during which of the following phases of the cell cycle?
A. S-phase
B. Anaphase
C. Prophase
D. Metaphase (Correct Answer)
E. Telophase
Explanation: ***Metaphase***
- The infant's features (flat face, upslanting palpebral fissures, epicanthal folds) are **characteristic of Down syndrome** (Trisomy 21).
- Karyotyping, which visualizes chromosomes to detect trisomies, is best performed during **metaphase** because chromosomes are maximally condensed and aligned at the metaphase plate, making them easily distinguishable.
*S-phase*
- During the **S-phase**, DNA replication occurs, and chromosomes are not yet condensed, making them unsuitable for microscopic visualization and karyotyping.
- This phase is primarily for **DNA synthesis**, not chromosomal analysis.
*Anaphase*
- In **anaphase**, sister chromatids separate and move to opposite poles of the cell.
- While chromosomes are visible, they are in motion, making it challenging to **accurately count and analyze their structure**.
*Prophase*
- **Prophase** involves the condensation of chromosomes and the breakdown of the nuclear envelope.
- Chromosomes are still condensing in prophase and not yet fully aligned, making them less ideal for detailed **karyotype analysis compared to metaphase**.
*Telophase*
- In **telophase**, chromosomes decondense, the nuclear envelope reforms, and the cell divides into two.
- Chromosomes are no longer discrete or condensed enough for **accurate visualization and karyotyping** during this phase.
Question 92: A 7-year-old girl presents to her primary care physician for a routine check-up. The physician allows the medical student to perform a physical examination. The medical student notes hearing impairment as well as the findings show in Figures A and B. Radiographs show indications of multiple old fractures of the humerus that have healed. After questioning the girl’s parents, the medical student learns that in addition, the patient is extremely picky with her food and eats a diet consisting mainly of cereal and pasta. What is the most likely etiology of the patient’s disease?
A. Dietary deficiency of ascorbic acid
B. Defect in type I collagen (Correct Answer)
C. Defective mineralization of cartilage
D. Decreased bone mineral density
E. Non-accidental trauma
Explanation: ***Defect in type I collagen***
- The constellation of **frequent fractures**, **hearing impairment**, and **blue sclerae** (as indicated by Figure A, which shows a bluish tint to the white part of the eye) is characteristic of **osteogenesis imperfecta (OI)**, a genetic disorder caused by mutations in COL1A1 or COL1A2 genes leading to **defective type I collagen synthesis**.
- Type I collagen is the primary structural protein in bone, and defects result in brittle bones, blue sclerae (due to thin sclera allowing choroid visibility), and conductive hearing loss (from ossicle abnormalities).
- While the patient's diet is described as "picky," the primary features point towards a genetic collagen defect rather than a nutritional deficiency as the underlying cause for the bone and connective tissue abnormalities.
*Dietary deficiency of ascorbic acid*
- A deficiency in **ascorbic acid (vitamin C)** leads to **scurvy**, characterized by **gingivitis**, **poor wound healing**, **petechiae**, and easy bruising due to impaired collagen synthesis.
- While collagen synthesis is affected, the specific presentation of blue sclerae, hearing impairment, and multiple fractures as primary symptoms is not typical for scurvy.
*Defective mineralization of cartilage*
- **Defective mineralization of cartilage** often points to **rickets in children** or **osteomalacia in adults**, usually due to **vitamin D deficiency** or disorders of phosphate metabolism.
- While these conditions can cause bone fragility, they do not typically present with blue sclerae or hearing impairment as defining features. The "old fractures" suggest a chronic bone fragility predating any acute nutritional issues.
*Decreased bone mineral density*
- **Decreased bone mineral density (BMD)** is a general term seen in many conditions, including **osteoporosis** and **osteogenesis imperfecta**.
- While the patient likely has decreased BMD due to their frequent fractures, this option describes a symptom rather than the **underlying etiology** of the disorder.
*Non-accidental trauma*
- **Non-accidental trauma (child abuse)** should always be considered in a child with multiple fractures.
- However, the presence of other systemic findings like **blue sclerae** and **hearing impairment** strongly suggests an underlying genetic disorder like osteogenesis imperfecta, making non-accidental trauma less likely as the primary cause for all observed symptoms.
Question 93: An investigator is studying human genetics and cell division. A molecule is used to inhibit the exchange of genetic material between homologous chromosomes. Which of the following phases of the cell cycle does the molecule target?
A. Prophase II
B. Prophase I (Correct Answer)
C. Metaphase II
D. Telophase I
E. Anaphase I
Explanation: ***Prophase I***
- **Crossing over** (genetic recombination) occurs specifically during **Prophase I** of meiosis, particularly during the pachytene stage
- During this phase, homologous chromosomes pair up (synapsis) and exchange genetic material through recombination
- Inhibiting this exchange means targeting the phase where this critical genetic recombination takes place
*Prophase II*
- Prophase II is a stage in meiosis II where chromosomes condense again after a brief interkinesis
- **Crossing over does not occur** in Prophase II - genetic recombination has already been completed in Prophase I
- Homologous chromosomes are no longer paired at this stage
*Metaphase II*
- During Metaphase II, individual chromosomes (not homologous pairs) align along the metaphase plate
- There is **no exchange of genetic material** between homologous chromosomes at this stage
- This phase prepares for the separation of sister chromatids
*Telophase I*
- Telophase I involves decondensation of chromosomes and reformation of nuclear envelopes around the separated homologous chromosomes
- This marks the end of meiosis I, **after** genetic exchange has already occurred in Prophase I
- No crossing over occurs during this phase
*Anaphase I*
- In Anaphase I, **homologous chromosomes separate** and move to opposite poles of the cell
- This phase is characterized by segregation of chromosomes, **not genetic exchange**
- Crossing over has already been completed by this stage
Question 94: A 2-month-old boy is brought to the physician by his mother because of poor weight gain and irritability since delivery. He is at the 10th percentile for height and below the 5th percentile for weight. Physical examination shows conjunctival pallor. Laboratory studies show:
Hemoglobin 11.2 g/dL
Mean corpuscular hemoglobin 24.2 pg/cell
Mean corpuscular volume 108 μm3
Serum
Ammonia 26 μmol/L (N=11–35 μmol/L)
A peripheral blood smear shows macrocytosis of erythrocytes and hypersegmented neutrophils. Supplementation with folate and cobalamin is begun. Two months later, his hemoglobin concentration is 11.1 g/dL and mean corpuscular volume is 107 μm3. The patient's condition is most likely caused by failure of which of the following enzymatic reactions?
A. Hypoxanthine to inosine monophosphate
B. Glucose-6-phosphate to 6-phosphogluconate
C. Ornithine and carbamoylphosphate to citrulline
D. Phosphoenolpyruvate to pyruvate
E. Orotate to uridine 5'-monophosphate (Correct Answer)
Explanation: ***Orotate to uridine 5'-monophosphate***
- The patient presents with **macrocytic anemia**, as evidenced by an elevated MCV (108 μm3) and the presence of **hypersegmented neutrophils** on the peripheral smear, along with symptoms of poor weight gain and irritability.
- The failure of **orotate to uridine 5'-monophosphate** conversion is characteristic of **hereditary orotic aciduria**, a defect in pyrimidine synthesis that leads to the accumulation of orotic acid and megaloblastic anemia refractory to folate and cobalamin supplementation.
*Hypoxanthine to inosine monophosphate*
- This reaction is part of the **purine salvage pathway**, catalyzed by **hypoxanthine-guanine phosphoribosyltransferase (HGPRT)**.
- Deficiencies in HGPRT lead to **Lesch-Nyhan syndrome**, characterized by hyperuricemia, self-mutilation, and neurological symptoms, not megaloblastic anemia.
*Glucose-6-phosphate to 6-phosphogluconate*
- This is the initial step in the **pentose phosphate pathway**, catalyzed by **glucose-6-phosphate dehydrogenase (G6PD)**.
- G6PD deficiency can cause **hemolytic anemia** (often microcytic or normocytic), especially under oxidative stress, but not megaloblastic anemia with hypersegmented neutrophils.
*Ornithine and carbamoylphosphate to citrulline*
- This reaction is catalyzed by **ornithine transcarbamylase (OTC)**, a key enzyme in the **urea cycle**.
- OTC deficiency leads to **hyperammonemia**, but not megaloblastic anemia. The patient's ammonia level is within the normal range, ruling out a urea cycle disorder.
*Phosphoenolpyruvate to pyruvate*
- This is the final step in **glycolysis**, catalyzed by **pyruvate kinase**.
- Pyruvate kinase deficiency typically causes **chronic hemolytic anemia** (often normocytic or macrocytic with reticulocytosis), but without hypersegmented neutrophils or a defect in DNA synthesis as seen in megaloblastic anemia.
Question 95: Red-green color blindness, an X-linked recessive disorder, has an incidence of 1/200 in males in a certain population. What is the probability of a phenotypically normal male and female having a child with red-green color blindness?
A. 1/400 (Correct Answer)
B. 199/200
C. 99/100
D. 1/200
E. 1/100
Explanation: ***1/400***
- For X-linked recessive disorders, the incidence in males equals the allele frequency (q). Given that 1/200 males are affected, **q = 1/200**.
- In Hardy-Weinberg equilibrium, the frequency of carrier females is **2pq ≈ 2q** (since p ≈ 1). Therefore, carrier female frequency = 2 × (1/200) = **1/100**.
- A phenotypically normal couple from the general population can only have an affected child if the mother is a carrier (probability 1/100).
- When a normal male (X⁺Y) crosses with a carrier female (X⁺Xᶜ), the offspring probabilities are:
- 1/4 affected son (XᶜY) - **has color blindness**
- 1/4 normal son (X⁺Y)
- 1/4 carrier daughter (X⁺Xᶜ)
- 1/4 normal daughter (X⁺X⁺)
- **Total probability = P(mother is carrier) × P(affected child from carrier mother) = (1/100) × (1/4) = 1/400**
*1/200*
- This represents the allele frequency (q) or the incidence in males, not the probability of a random phenotypically normal couple having an affected child.
- It fails to account for the probability that the mother is a carrier (1/100) and the 1/4 chance of an affected child from a carrier mother.
*1/100*
- This value represents the frequency of carrier females (2pq ≈ 2q) in the population.
- It does not account for the additional 1/4 probability of having an affected child when the mother is a carrier.
*199/200*
- This represents the probability of a male NOT being affected (1 - q = 1 - 1/200).
- It is irrelevant to calculating the probability of a couple having an affected child.
*99/100*
- This likely represents the probability of a female NOT being a carrier.
- It does not address the question of producing an affected offspring from a phenotypically normal couple.
Question 96: A 9-month-old female is brought to the emergency department after experiencing a seizure. She was born at home and was normal at birth according to her parents. Since then, they have noticed that she does not appear to be achieving developmental milestones as quickly as her siblings, and often appears lethargic. Physical exam reveals microcephaly, very light pigmentation (as compared to her family), and a "musty" body odor. The varied manifestations of this disease can most likely be attributed to which of the following genetic principles?
A. Incomplete penetrance
B. Multiple gene mutations
C. Pleiotropy (Correct Answer)
D. Anticipation
E. Variable expressivity
Explanation: ***Pleiotropy***
- **Pleiotropy** refers to a single gene affecting multiple seemingly unrelated phenotypic traits, which is evident in this case of **phenylketonuria (PKU)** where a single enzyme deficiency (phenylalanine hydroxylase) leads to **seizures**, developmental delay, **microcephaly**, hypopigmentation, and a **"musty" odor**.
- The diverse clinical manifestations arise from the accumulation of phenylalanine and its metabolites, which are toxic to various organ systems, primarily the brain and also interfering with melanin synthesis.
*Incomplete penetrance*
- **Incomplete penetrance** describes a situation where individuals with a specific genotype do not always express the associated phenotype, meaning some might carry the gene but show no symptoms.
- This principle usually describes "all or nothing" manifestation of the disease, not varied manifestations of one disease.
*Multiple gene mutations*
- This principle applies when a disease is caused by defects in **several different genes** working together or independently, leading to a complex inheritance pattern.
- While many complex diseases involve multiple genes, the constellation of symptoms described (seizures, developmental delay, hypopigmentation, odor) in PKU points to a single primary defect with widespread effects.
*Anticipation*
- **Anticipation** describes a genetic phenomenon where the severity of disease increases and/or age of onset decreases in successive generations, typically seen in diseases like Huntington's or myotonic dystrophy due to unstable trinucleotide repeats.
- The clinical presentation in this child does not suggest a pattern of worsening symptoms across generations within the family.
*Variable expressivity*
- **Variable expressivity** describes how individuals with the same genotype can exhibit different clinical features or varying degrees of disease severity.
- While PKU can have variable expressivity (depending on dietary control or residual enzyme activity), the core concept explaining *why* so many *different types* of symptoms exist from a single gene defect is pleiotropy, not just variability in one type of symptom.
