A 9-year-old boy is getting fitted for leg braces because he has become too weak to walk without them. He developed normally until age 3 but then he began to get tired more easily and fell a lot. Over time he started having trouble walking and would stand up by using the Gower maneuver. Despite this weakness, his neurologic development is normal for his age. On exam his calves appeared enlarged and he was sent for genetic testing. Sequence data showed that he had a mutation causing a shift in the reading frame, resulting in a severely truncated and non-functional protein. Which of the following types of mutations is most likely the cause of this patient's disorder?
Q12
A 2-year-old male is referred to a geneticist for developmental delay and intellectual disability. He was hypotonic at birth and his parents are concerned that he tries to eat everything, including erasers and chalk. Physical exam is remarkable for severe obesity and hypogonadism. Genetic analysis reveals that he has one mutated allele and one normal allele at the gene of interest. Which of the following is the most likely explanation for why this patient is affected despite having a normal allele?
Q13
A clinical trial is being run with patients that have a genetic condition characterized by abnormal hemoglobin that can undergo polymerization when exposed to hypoxia, acidosis, or dehydration. This process of polymerization is responsible for the distortion of the red blood cell (RBC) that acquires a crescent shape and the hemolysis of RBCs. Researchers are studying the mechanisms of the complications commonly observed in these patients such as stroke, aplastic crisis, and auto-splenectomy. What kind of mutation leads to the development of the disease?
Q14
An 11-year-old boy who recently emigrated from Ukraine is brought to the physician for the evaluation of failure to thrive. Genetic analysis shows the deletion of the 508th codon in a gene on chromosome 7. The deletion results in defective post-translational folding of a protein and retention of the misfolded protein in the rough endoplasmic reticulum. The activity of which of the following channels is most likely to be increased as a result of the defect?
Q15
A 12-year-old boy develops muscle weakness and pain, vomiting, seizures, and severe headache. Additionally, he presents with hemiparesis on one side of the body. A muscle biopsy shows 'ragged red fibers'. What is true about the mode of inheritance of the disease described?
Q16
Replication in eukaryotic cells is a highly organized and accurate process. The process involves a number of enzymes such as primase, DNA polymerase, topoisomerase II, and DNA ligase. In which of the following directions is DNA newly synthesized?
Q17
An 8-year-old girl is brought to the pediatrician because she is significantly shorter than her classmates. Her mother notes that she has had thick, oral secretions for the past several months, along with a chronic cough. Her exam is notable for clubbed fingernails. Her pediatrician sends a genetic test for a transmembrane channel mutation, which shows a normal DNA sequence, except for the deletion of three nucleotides that code for a phenylalanine at position 508. What type of mutation has caused her presentation?
Q18
A 24-year-old man comes to the physician because his vision has worsened rapidly over the last 2 months. His maternal uncle lost his vision suddenly over a period of 3 months at 26 years of age. The patient's wife and 1-year-old son have normal vision. Funduscopic examination of the patient shows bilateral circumpapillary telangiectasia. Genetic testing shows a missense mutation in one of the genes of the electron transport chain complexes. The probability that this patient's son will be affected by the same disease is closest to which of the following?
Q19
An investigator is studying the interaction between epithelial cells and calcium ion concentration. When the calcium ion concentration available to a sample of epithelial tissue is decreased, an increased gap between adjacent epithelial cells is seen on electron microscopy. This observed decrease in cell adhesion is most likely due to an effect on which of the following proteins?
Q20
A 14-year-old boy is brought to the physician because of blurry vision. He is at the 97th percentile for height and 25th percentile for weight. He has long, slender fingers and toes that are hyperflexible. Examination of the oropharynx shows a high-arched palate. Slit lamp examination shows bilateral lens subluxation in the superotemporal direction. The patient's older sister is also tall and has hyperflexible joints. However, she does not have lens subluxation or an arched palate. Which of the following genetic principles accounts for the phenotypical differences seen in this pair of siblings?
Molecular Genetics US Medical PG Practice Questions and MCQs
Question 11: A 9-year-old boy is getting fitted for leg braces because he has become too weak to walk without them. He developed normally until age 3 but then he began to get tired more easily and fell a lot. Over time he started having trouble walking and would stand up by using the Gower maneuver. Despite this weakness, his neurologic development is normal for his age. On exam his calves appeared enlarged and he was sent for genetic testing. Sequence data showed that he had a mutation causing a shift in the reading frame, resulting in a severely truncated and non-functional protein. Which of the following types of mutations is most likely the cause of this patient's disorder?
A. Splice site
B. Missense
C. Nonsense
D. Frameshift (Correct Answer)
E. Silent
Explanation: ***Frameshift***
- A **frameshift mutation** is caused by the insertion or deletion of nucleotides not in multiples of three, leading to a shift in the reading frame of the mRNA. This results in altered codons downstream of the mutation, typically leading to a **premature stop codon** and a **severely truncated, non-functional protein**.
- The description of a mutation causing "a shift in the reading frame, resulting in a severely truncated and non-functional protein" is characteristic of a frameshift mutation, which is the most common type of mutation in **Duchenne muscular dystrophy** (DMD). The clinical picture (onset around age 3-5, progressive proximal weakness, Gower maneuver, calf pseudohypertrophy) is classic for DMD.
- In DMD, frameshift mutations in the dystrophin gene lead to complete loss of functional dystrophin protein, causing the severe progressive muscle weakness seen in this patient.
*Splice site*
- A **splice site mutation** affects the recognition sequences for intron-exon boundaries during mRNA splicing, potentially leading to exon skipping, intron retention, or use of cryptic splice sites. While splice site mutations can cause DMD (accounting for ~10% of cases), they are less common than frameshifts/deletions.
- The specific description of a "shift in the reading frame" points more directly to a frameshift mutation rather than a splicing defect.
*Missense*
- A **missense mutation** results in a single nucleotide substitution that changes one codon to specify a different amino acid. This produces a full-length protein with a single amino acid substitution.
- Missense mutations typically cause the milder **Becker muscular dystrophy** phenotype (with partially functional dystrophin), not the severe Duchenne phenotype described here. The description of a "severely truncated and non-functional protein" does not fit a missense mutation.
*Nonsense*
- A **nonsense mutation** introduces a premature stop codon directly by changing a codon that normally specifies an amino acid into a stop codon (UAG, UAA, or UGA). This results in a truncated protein.
- While nonsense mutations can cause DMD and do produce truncated proteins, the specific wording "shift in the reading frame" is more characteristic of a frameshift mutation. Nonsense mutations don't shift the reading frame—they directly create a stop signal.
*Silent*
- A **silent (synonymous) mutation** is a nucleotide substitution that does not change the amino acid sequence due to the degeneracy of the genetic code (multiple codons can specify the same amino acid).
- Silent mutations produce normal, full-length proteins and would not cause disease symptoms.
Question 12: A 2-year-old male is referred to a geneticist for developmental delay and intellectual disability. He was hypotonic at birth and his parents are concerned that he tries to eat everything, including erasers and chalk. Physical exam is remarkable for severe obesity and hypogonadism. Genetic analysis reveals that he has one mutated allele and one normal allele at the gene of interest. Which of the following is the most likely explanation for why this patient is affected despite having a normal allele?
A. Uniparental disomy
B. X-linked inheritance pattern
C. Locus heterogeneity
D. Autosomal dominant inheritance pattern
E. Imprinting (Correct Answer)
Explanation: ***Imprinting***
- The constellation of **hypotonia**, **developmental delay**, **hyperphagia** (eating everything), **obesity**, and **hypogonadism** is characteristic of **Prader-Willi syndrome**.
- **Prader-Willi syndrome** is typically caused by the **loss of function of specific paternally inherited genes** on chromosome 15 (15q11-q13), a mechanism known as **genomic imprinting**, where only one parent's copy of a gene is active.
- In this case, the patient has one mutated (paternal) allele and one normal but imprinted/silenced (maternal) allele, explaining why disease occurs despite the presence of a structurally normal allele.
*Uniparental disomy*
- **Maternal uniparental disomy** of chromosome 15 can also cause Prader-Willi syndrome if both copies of the chromosome are inherited from the mother, leading to no functional paternal genes.
- However, the question explicitly states "one mutated allele and one normal allele," which describes a **deletion or mutation of the paternal copy** rather than UPD (where both chromosomes would be from the mother and appear structurally normal on standard testing).
- The question asks for the *mechanism* explaining why the patient is affected despite having a normal allele - the answer is **imprinting**, which is the underlying mechanism in both deletion and UPD cases.
*X-linked inheritance pattern*
- **X-linked inheritance** typically affects males more severely with different phenotypic presentations and does not explain the combination of a normal and mutated allele resulting in the specific Prader-Willi phenotype.
- The described syndrome (Prader-Willi) is associated with **chromosome 15** abnormalities, not the X chromosome.
*Locus heterogeneity*
- **Locus heterogeneity** describes a single disease phenotype caused by mutations in different gene loci, which is not relevant to explaining why a single mutated allele results in disease in the context of Prader-Willi syndrome.
- The clinical picture strongly points to a specific genetic disorder with a known genetic cause on a single locus.
*Autosomal dominant inheritance pattern*
- While **autosomal dominant disorders** manifest with one mutated allele, the specific combination of symptoms with obesity, hypogonadism, and hyperphagia in this scenario is not typical for a general autosomal dominant pattern.
- The question describes features characteristic of **Prader-Willi syndrome**, which is primarily an **imprinting disorder**, rather than a straightforward autosomal dominant condition where the presence of one normal allele would be expected to provide sufficient function in the absence of imprinting.
Question 13: A clinical trial is being run with patients that have a genetic condition characterized by abnormal hemoglobin that can undergo polymerization when exposed to hypoxia, acidosis, or dehydration. This process of polymerization is responsible for the distortion of the red blood cell (RBC) that acquires a crescent shape and the hemolysis of RBCs. Researchers are studying the mechanisms of the complications commonly observed in these patients such as stroke, aplastic crisis, and auto-splenectomy. What kind of mutation leads to the development of the disease?
A. Silent mutation
B. Splice site
C. Missense mutation (Correct Answer)
D. Nonsense mutation
E. Frameshift mutation
Explanation: ***Missense mutation***
- A missense mutation results in a **single nucleotide substitution** that changes the codon to code for a different amino acid, altering the protein.
- In **sickle cell disease**, a missense mutation in the beta-globin gene (GAG to GTG) leads to the substitution of **glutamic acid for valine**, causing abnormal hemoglobin (HbS) that polymerizes under deoxygenated conditions.
*Silent mutation*
- A silent mutation is a **point mutation** that results in a new codon that still codes for the **same amino acid**, meaning there is no change in the protein sequence.
- Therefore, it would not lead to an **abnormal hemoglobin** protein or the described disease phenotype.
*Splice site*
- A splice site mutation occurs at the **splice junctions** of introns and exons, leading to errors in mRNA processing.
- This can result in **incorrect protein synthesis** due to exon skipping or intron retention, but it typically does not cause the specific amino acid substitution seen in sickle cell disease.
*Nonsense mutation*
- A nonsense mutation is a point mutation that results in a **premature stop codon**, leading to a **truncated, non-functional protein**.
- While this can cause severe disease, it would typically lead to a complete absence or severe deficiency of functional hemoglobin rather than a structurally altered hemoglobin like HbS.
*Frameshift mutation*
- A frameshift mutation involves the **insertion or deletion of nucleotides** (not in multiples of three), which shifts the reading frame of the mRNA.
- This typically leads to a completely **altered amino acid sequence** downstream of the mutation and usually results in a premature stop codon, leading to a non-functional protein rather than a specific single amino acid substitution.
Question 14: An 11-year-old boy who recently emigrated from Ukraine is brought to the physician for the evaluation of failure to thrive. Genetic analysis shows the deletion of the 508th codon in a gene on chromosome 7. The deletion results in defective post-translational folding of a protein and retention of the misfolded protein in the rough endoplasmic reticulum. The activity of which of the following channels is most likely to be increased as a result of the defect?
A. Calcium channels of distal tubular cells
B. ATP-sensitive potassium channels of pancreatic beta cells
C. Bicarbonate channels of pancreatic ductal cells
D. Chloride channels of epithelial cells in sweat glands
E. Sodium channels of respiratory epithelial cells (Correct Answer)
Explanation: ***Sodium channels of respiratory epithelial cells***
- The patient's presentation with **failure to thrive**, genetic defect (deletion of codon 508 on chromosome 7), and **defective protein folding** are classic for **cystic fibrosis (CF)**.
- In CF, the defective **CFTR protein** (a chloride channel) leads to reduced chloride secretion and increased **sodium absorption** in respiratory epithelial cells, causing thickened mucus.
*Calcium channels of distal tubular cells*
- Dysfunction of **calcium channels** in the distal tubules is not a primary feature of cystic fibrosis.
- Renal calcium handling issues are typically associated with conditions like **Dent's disease** or various types of **renal tubular acidosis**, not CF.
*ATP-sensitive potassium channels of pancreatic beta cells*
- While CF can lead to pancreatic insufficiency and **CF-related diabetes**, the primary defect is not in the **ATP-sensitive potassium channels** of beta cells.
- The insulin deficiency in CF diabetes is due to destruction of pancreatic islets secondary to duct obstruction and inflammation.
*Bicarbonate channels of pancreatic ductal cells*
- In cystic fibrosis, the **CFTR protein** is a chloride channel that also facilitates bicarbonate transport, and its dysfunction does impair **bicarbonate secretion** in pancreatic ductal cells.
- However, the question specifically asks about an *increase* in channel activity, and bicarbonate channel activity is *decreased* in CF.
*Chloride channels of epithelial cells in sweat glands*
- The **CFTR protein** is indeed a **chloride channel** in sweat glands, and in CF, its *activity is decreased*, leading to reduced chloride reabsorption and high sweat chloride (the basis for the sweat test).
- The question asks for an *increased* channel activity, which is seen with sodium channels due to the linked transport mechanisms.
Question 15: A 12-year-old boy develops muscle weakness and pain, vomiting, seizures, and severe headache. Additionally, he presents with hemiparesis on one side of the body. A muscle biopsy shows 'ragged red fibers'. What is true about the mode of inheritance of the disease described?
A. Skips generations
B. Commonly more severe in males
C. It can be transmitted through both parents.
D. It is transmitted only through the mother. (Correct Answer)
E. Mothers transmit to 50% of daughters and sons
Explanation: ***It is transmitted only through the mother.***
- The constellation of symptoms (muscle weakness, pain, vomiting, seizures, severe headache, hemiparesis) and the presence of **"ragged red fibers"** on muscle biopsy are classic findings in **Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome**.
- **Mitochondrial disorders**, including MELAS, are inherited exclusively from the mother because ova contribute mitochondria to the zygote, while sperm contribute virtually none.
*Mothers transmit to 50% of daughters and son*
- This statement describes the inheritance pattern of an **X-linked recessive** or, in some cases, **autosomal dominant** trait with incomplete penetrance, which is not characteristic of mitochondrial inheritance.
- In mitochondrial inheritance, all offspring (100%) of an affected mother will inherit the mitochondrial DNA, though the penetrance and expressivity can vary.
*Skips generations*
- "Skipping generations" is a hallmark of **recessive inheritance patterns**, where affected individuals may have unaffected parents who are carriers.
- This is not typical for **mitochondrial inheritance**, where the disease is usually present in every generation through the maternal line.
*Commonly more severe in males*
- While some genetic conditions show sex-specific severity, such as X-linked disorders that are often more severe in males due to having only one X chromosome, this is not a general rule for **mitochondrial diseases**.
- The severity of mitochondrial disorders is often related to the **proportion of mutated mitochondrial DNA (heteroplasmy)**, which can vary between sexes and tissues.
*It can be transmitted through both parents.*
- This statement generally describes **autosomal recessive** or **autosomal dominant** inheritance patterns, where genetic material from both parents contributes to the child's genotype.
- **Mitochondrial inheritance** is exclusively maternal, as only the mother contributes mitochondria to the offspring.
Question 16: Replication in eukaryotic cells is a highly organized and accurate process. The process involves a number of enzymes such as primase, DNA polymerase, topoisomerase II, and DNA ligase. In which of the following directions is DNA newly synthesized?
A. 3' --> 5'
B. N terminus --> C terminus
C. C terminus --> N terminus
D. 3' --> 5' & 5' --> 3'
E. 5' --> 3' (Correct Answer)
Explanation: ***5' --> 3'***
- DNA polymerase can only add **nucleotides** to the 3' end of a growing strand, meaning synthesis always proceeds in a **5' to 3' direction**.
- This is true for both the **leading strand** (synthesized continuously) and the **lagging strand** (synthesized discontinuously via Okazaki fragments).
*3' --> 5'*
- While the parental template strand is read in the 3' to 5' direction, the *newly synthesized* DNA strand is always built in the **opposite, antiparallel 5' to 3' direction**.
- DNA polymerase lacks the ability to add new nucleotides to the **5' phosphate group** of the growing strand.
*N terminus --> C terminus*
- This directional notation refers to the synthesis of **proteins**, where amino acids are added to the C (carboxyl) terminus of the growing polypeptide chain.
- It does not apply to the synthesis direction of **nucleic acids (DNA or RNA)**.
*C terminus --> N terminus*
- This directional notation is incorrectly applied; protein synthesis always proceeds from the **N (amino) terminus to the C (carboxyl) terminus**.
- This has no relevance to the synthesis direction of **DNA**.
*3' --> 5' & 5' --> 3'*
- Although DNA replication involves two strands, one is synthesized continuously in the **5' → 3' direction (leading strand)** and the other discontinuously, but still *each fragment* is synthesized in the **5' → 3' direction (lagging strand)**.
- No new DNA strand is synthesized in the **3' → 5' direction**.
Question 17: An 8-year-old girl is brought to the pediatrician because she is significantly shorter than her classmates. Her mother notes that she has had thick, oral secretions for the past several months, along with a chronic cough. Her exam is notable for clubbed fingernails. Her pediatrician sends a genetic test for a transmembrane channel mutation, which shows a normal DNA sequence, except for the deletion of three nucleotides that code for a phenylalanine at position 508. What type of mutation has caused her presentation?
A. Triplet expansion
B. Nonsense mutation
C. Frameshift mutation
D. In-frame mutation (Correct Answer)
E. Silent mutation
Explanation: ***In-frame mutation***
- The deletion of three nucleotides, which together code for a single amino acid (phenylalanine), results in an **in-frame mutation** because the reading frame of the mRNA is maintained.
- This specific mutation is **ΔF508**, the most common mutation in **cystic fibrosis (CF)**, consistent with the patient's symptoms of growth failure, thick secretions, chronic cough, and clubbed fingernails.
*Triplet expansion*
- This involves the **increase in the number of repeats of a trinucleotide sequence**, such as in Huntington's disease or fragile X syndrome.
- The patient's mutation is a **deletion**, not an expansion of a trinucleotide repeat.
*Nonsense mutation*
- A nonsense mutation involves a **point mutation** that results in a **premature stop codon**, leading to a truncated protein.
- The patient's mutation is a **deletion of an entire codon**, not a single base change leading to a stop codon.
*Frameshift mutation*
- A frameshift mutation occurs when the deletion or insertion of nucleotides is **not a multiple of three**, leading to a shift in the reading frame and alteration of all downstream amino acids.
- In this case, the deletion of **three nucleotides** maintains the reading frame, so it is not a frameshift.
*Silent mutation*
- A silent mutation is a **point mutation** where a change in a single nucleotide does not alter the amino acid sequence due to the degeneracy of the genetic code.
- Here, the **deletion of a codon** results in the loss of an amino acid, clearly altering the protein product, hence it is not silent.
Question 18: A 24-year-old man comes to the physician because his vision has worsened rapidly over the last 2 months. His maternal uncle lost his vision suddenly over a period of 3 months at 26 years of age. The patient's wife and 1-year-old son have normal vision. Funduscopic examination of the patient shows bilateral circumpapillary telangiectasia. Genetic testing shows a missense mutation in one of the genes of the electron transport chain complexes. The probability that this patient's son will be affected by the same disease is closest to which of the following?
A. 33%
B. 100%
C. 0% (Correct Answer)
D. 25%
E. 50%
Explanation: ***0%***
- This condition, **Leber's Hereditary Optic Neuropathy (LHON)**, is caused by a mutation in **mitochondrial DNA**.
- **Mitochondrial DNA** is exclusively inherited from the mother, meaning the father cannot pass it on to his children.
*33%*
- This percentage does not align with any known pattern of Mendelian inheritance or mitochondrial inheritance.
- It would be too low for a dominant mitochondrial disorder and too high for a recessive one if the mother were a carrier.
*100%*
- While all children of an affected mother would inherit the disease, the patient is a male, and mitochondria are inherited maternally.
- Therefore, the father cannot pass on his **mitochondrial DNA** to his son.
*25%*
- This percentage is typically associated with **autosomal recessive inheritance**, where both parents are carriers.
- LHON follows a **mitochondrial inheritance pattern**, which is distinct from autosomal inheritance.
*50%*
- This percentage is characteristic of **autosomal dominant inheritance** or X-linked recessive inheritance where the mother is a carrier.
- Since this is a **mitochondrial disorder**, the father's genes are not involved in transmission to his son.
Question 19: An investigator is studying the interaction between epithelial cells and calcium ion concentration. When the calcium ion concentration available to a sample of epithelial tissue is decreased, an increased gap between adjacent epithelial cells is seen on electron microscopy. This observed decrease in cell adhesion is most likely due to an effect on which of the following proteins?
A. Actin
B. Integrin
C. Cadherin (Correct Answer)
D. Claudin
E. Cytokeratin
Explanation: ***Cadherin***
- **Cadherins** are calcium-dependent adhesion proteins that mediate cell-to-cell adhesion, particularly in epithelial tissues.
- A decrease in calcium concentration would directly impair cadherin function, leading to reduced cell adhesion and increased intercellular gaps.
*Actin*
- **Actin** is a component of the cell's cytoskeleton, involved in cell shape, motility, and intracellular transport, but not directly responsible for calcium-dependent cell adhesion between epithelial cells.
- While actin filaments interact with adhesion junctions, their primary role is structural and dynamic rather than adhesive.
*Integrin*
- **Integrins** are primarily involved in cell-to-extracellular matrix adhesion, connecting the cell to the surrounding matrix, not directly mediating calcium-dependent cell-to-cell adhesion between epithelial cells.
- They can be affected by intracellular calcium signaling but do not directly bind calcium to mediate their adhesive function in the same way cadherins do.
*Claudin*
- **Claudins** are key components of **tight junctions**, which regulate paracellular permeability and form a barrier between cells, but they are not directly responsible for calcium-dependent cell-to-cell adhesion, which is characteristic of adherens junctions.
- While tight junctions contribute to overall cell-cell contact, the observation of an *increased gap* suggests an issue with adhesive complexes like adherens junctions, where cadherins are prominent.
*Cytokeratin*
- **Cytokeratins** are intermediate filaments found in epithelial cells, providing structural support and mechanical strength.
- They are linked to desmosomes and hemidesmosomes but are not directly involved in calcium-dependent cell-to-cell adhesion.
Question 20: A 14-year-old boy is brought to the physician because of blurry vision. He is at the 97th percentile for height and 25th percentile for weight. He has long, slender fingers and toes that are hyperflexible. Examination of the oropharynx shows a high-arched palate. Slit lamp examination shows bilateral lens subluxation in the superotemporal direction. The patient's older sister is also tall and has hyperflexible joints. However, she does not have lens subluxation or an arched palate. Which of the following genetic principles accounts for the phenotypical differences seen in this pair of siblings?
A. Incomplete penetrance
B. Frameshift mutation
C. Compound heterozygosity
D. Variable expressivity (Correct Answer)
E. Chromosomal instability
Explanation: ***Variable expressivity***
- This principle accounts for the **range of phenotypes** observed among individuals who carry the same genetic mutation, as seen in the siblings with Marfan syndrome.
- Both siblings likely have the same genetic defect (e.g., in the *FBN1* gene), but express different combinations and severity of symptoms.
*Incomplete penetrance*
- This occurs when individuals with a specific genotype **do not always express** the associated phenotype.
- In this case, both siblings *do* express some features of Marfan syndrome, indicating that the gene is penetrant in both.
*Frameshift mutation*
- A frameshift mutation is a type of **gene mutation** caused by indels (insertions or deletions) of a number of nucleotides not divisible by three.
- While a frameshift mutation could be the underlying cause of Marfan syndrome, it does not explain the *phenotypical differences* between two individuals with the same underlying genetic defect.
*Compound heterozygosity*
- This describes a situation where an individual has **two different mutant alleles** at the same gene locus, one on each chromosome.
- While relevant to some genetic disorders, it does not explain the phenotypic variability between two siblings who inherited the same underlying genetic susceptibility.
*Chromosomal instability*
- This refers to a high rate of **chromosome rearrangements** or aneuploidy (abnormal chromosome number) within cells.
- While it can lead to various medical conditions, it is not the mechanism primarily responsible for the varying phenotypes of a single-gene disorder like Marfan syndrome in different individuals.
