Genetics of Common Diseases — MCQs
A 25-year-old man presents for a routine examination and is found to have an early diastolic murmur on examination. Clinical findings suggest hypertrophic cardiomyopathy. The family pedigree shows affected individuals in three consecutive generations with both males and females affected, and no generation is skipped. What is the most likely mode of inheritance of this genetic condition?
Which of the following disorders is most commonly associated with multifactorial inheritance?
Mutation in GLUT-2 causes which syndrome?
What is the interpretation of the given pedigree chart?
A 14-year-old male presents with type I diabetes mellitus. His mother wants to know if the boy's brother might also have an increased risk of getting the disease. Which of the following genotypes, if present in the brother, would be associated with the greatest risk of developing diabetes?
Which enzymatic activity is primarily responsible for the immortality of cancer cells?
Mutations are due to changes in:
In which of the following inheritance patterns is father-to-son transmission not observed?
A patient diagnosed with an isolated increase in LDL, with a family history of the same disease in his father and brother, is likely to have a diagnosis of
Wilson's disease has which of the following inheritance?
Genetics of Common Diseases Indian Medical PG Practice Questions and MCQs
Question 1: A 25-year-old man presents for a routine examination and is found to have an early diastolic murmur on examination. Clinical findings suggest hypertrophic cardiomyopathy. The family pedigree shows affected individuals in three consecutive generations with both males and females affected, and no generation is skipped. What is the most likely mode of inheritance of this genetic condition?
- A. AD (Correct Answer)
- B. AR
- C. XLD
- D. XLR
Explanation: ***AD (Autosomal Dominant)*** - The presence of affected individuals in **three consecutive generations** without skipping generations is a hallmark of autosomal dominant inheritance [1]. - Both **males and females are affected** equally, indicating it is not X-linked [1]. *AR (Autosomal Recessive)* - **Autosomal recessive** conditions typically **skip generations** and affect siblings, as carriers can pass on the gene without expressing the disease. - Such conditions often show a **25% recurrence risk** in offspring of two carrier parents, which is not suggested here. *XLD (X-linked Dominant)* - **X-linked dominant** inheritance would show **affected fathers passing the trait to all their daughters** but none of their sons, which is not specified. - Affected mothers would have a **50% chance** of passing the trait to each child, regardless of sex. *XLR (X-linked Recessive)* - **X-linked recessive** conditions predominantly affect **males**, and affected fathers cannot pass the trait to their sons. - Females are typically carriers, and affected males often have unaffected parents, which would imply skipping generations.
Question 2: Which of the following disorders is most commonly associated with multifactorial inheritance?
- A. Achondroplasia
- B. Lysosomal storage disease
- C. Cleft lip (Correct Answer)
- D. Huntington disease
Explanation: ***Cleft lip*** - **Cleft lip** is a classic example of a **multifactorial disorder**, resulting from the interaction of multiple genes and environmental factors. - Its recurrence risk is typically observed to be around 2-5% in affected families, consistent with **multifactorial inheritance**. *Achondroplasia* - Achondroplasia is an **autosomal dominant disorder**, caused by a single gene mutation in the **FGFR3 gene**. - It does not primarily involve the complex interplay of multiple genes and environmental factors characteristic of multifactorial inheritance. *Lysosomal storage disease* - Lysosomal storage diseases are a group of **autosomal recessive disorders**, each caused by a defect in a specific lysosomal enzyme. - They follow classic **Mendelian inheritance patterns** rather than multifactorial models. *Huntington disease* - Huntington disease is an **autosomal dominant neurodegenerative disorder**, caused by a trinucleotide repeat expansion in the **HTT gene**. - It exhibits a clear dominant inheritance pattern and does not involve multiple genes or significant environmental contributions in its etiology.
Question 3: Mutation in GLUT-2 causes which syndrome?
- A. Dandy walker syndrome
- B. Beckwith-Wiedemann syndrome
- C. Menke's disease
- D. Fanconi-Bickel syndrome (Correct Answer)
Explanation: ***Fanconi-Bickel syndrome*** - This syndrome is caused by a **mutation in the GLUT-2 gene**, leading to dysfunctional glucose transport in the liver, kidneys, and intestines. - Key features include **hepatorenal glycogen accumulation**, **renal tubulopathy** (Fanconi syndrome), and **impaired glucose and galactose utilization**. *Dandy-Walker syndrome* - This is a **congenital brain malformation** involving the cerebellum and fourth ventricle. - It is often associated with hydrocephalus, but not directly linked to glucose transporter defects. *Beckwith-Wiedemann syndrome* - This is an **overgrowth disorder** characterized by a high risk of childhood cancer and congenital anomalies. - It is primarily caused by genetic abnormalities on **chromosome 11p15.5** and is unrelated to GLUT-2 mutations. *Menke's disease* - This is a rare X-linked recessive disorder of **copper metabolism**, leading to severe neurological degeneration. - It results from mutations in the **ATP7A gene**, which encodes a copper-transporting ATPase.
Question 4: What is the interpretation of the given pedigree chart?
- A. Autosomal dominant (Correct Answer)
- B. Incomplete penetrance
- C. Autosomal recessive
- D. X-linked dominant
Explanation: ***Autosomal dominant*** - The trait appears in **every generation**, indicated by affected individuals in the first, second, and third generations [1]. - Both males and females are affected relatively equally, and affected individuals transmit the trait to approximately half of their offspring, consistent with **vertical transmission** [1]. - **Male-to-male transmission** is present, which definitively rules out X-linked inheritance patterns [1]. *Incomplete penetrance* - This pattern would typically show some individuals who carry the disease-causing genotype but **do not express the phenotype** (unaffected). - In this pedigree, all individuals who are expected to express the trait based on the clear dominant pattern are indeed affected. *Autosomal recessive* - This mode of inheritance would typically show **skipped generations**, meaning affected individuals would often have unaffected parents who are carriers [1]. - In this chart, every affected individual has at least one affected parent, ruling out an autosomal recessive pattern [1]. X-linked dominant - In X-linked dominant inheritance, **no male-to-male transmission** would be observed, as fathers pass their X chromosome only to daughters. - The presence of affected males transmitting the trait to male offspring rules out this inheritance pattern. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 148-151.
Question 5: A 14-year-old male presents with type I diabetes mellitus. His mother wants to know if the boy's brother might also have an increased risk of getting the disease. Which of the following genotypes, if present in the brother, would be associated with the greatest risk of developing diabetes?
- A. DR2/DR4
- B. DR3/DR4 (Correct Answer)
- C. DR2/DR2
- D. B27/B27
Explanation: ***DR3/DR4*** - The combination of **HLA-DR3** and **HLA-DR4** is the strongest genetic risk factor for **Type 1 diabetes mellitus (T1DM)**, particularly in individuals of European descent. - These alleles are associated with increased susceptibility to autoimmune destruction of pancreatic beta cells [1]. *DR2/DR4* - While **DR4** is a risk allele for Type 1 diabetes, **DR2 (specifically DRB1*1501)** is generally considered to be protective against the disease. - The presence of the protective DR2 allele would likely mitigate the increased risk conferred by DR4. *DR2/DR2* - **HLA-DR2 (DRB1*1501)** is largely recognized as a protective allele against **Type 1 diabetes**, meaning individuals with this genotype have a lower risk of developing the disease [1]. - Its presence is associated with a reduced susceptibility to autoimmune conditions like T1DM. *B27/B27* - **HLA-B27** is primarily associated with **seronegative spondyloarthropathies** such as ankylosing spondylitis and reactive arthritis, and not directly with an increased risk of Type 1 diabetes mellitus. - This allele is involved in different autoimmune pathways than those implicated in T1DM.
Question 6: Which enzymatic activity is primarily responsible for the immortality of cancer cells?
- A. RNA polymerase
- B. Telomerase (Correct Answer)
- C. DNA polymerase
- D. DNA reverse transcriptase
Explanation: ***Telomerase*** - **Telomerase** is an enzyme that adds repetitive nucleotide sequences to the ends of chromosomes (**telomeres**), preventing their shortening during DNA replication [1]. - In normal somatic cells, **telomerase** activity is low or absent, leading to progressive telomere shortening and eventual cellular senescence or apoptosis; however, in cancer cells, **telomerase** is highly active, maintaining telomere length and enabling indefinite cell division, contributing to their **immortality** [1]. *DNA reverse transcriptase* - **DNA reverse transcriptase** synthesizes DNA from an RNA template, a process characteristic of retroviruses (e.g., HIV) and not typically involved in the immortality of human cancer cells. - While some endogenous retroelements exist in the human genome, this enzyme's primary role is not in maintaining the replicative potential of cancer cells. *RNA polymerase* - **RNA polymerase** is responsible for synthesizing RNA from a DNA template (**transcription**), a fundamental process in gene expression. - While critical for cell growth and division, **RNA polymerase** does not directly prevent telomere shortening or contribute to cellular immortality. *DNA polymerase* - **DNA polymerase** is involved in DNA replication and repair, synthesizing new DNA strands and ensuring genetic fidelity. - While essential for cell proliferation, it does not directly address the issue of **telomere shortening**, which is key to cellular aging and immortality. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 311-312.
Question 7: Mutations are due to changes in:
- A. DNA nucleotide sequence (Correct Answer)
- B. RNA nucleotide sequence
- C. Amino acid sequence of ribonuclease
- D. Cell membrane
Explanation: ***DNA nucleotide sequence*** - **Mutations** are defined as changes in the **genetic material**, which is primarily composed of **DNA**. - These changes in the **nucleotide sequence** of DNA can alter the genetic code, leading to changes in **protein structure and function**. *RNA nucleotide sequence* - While RNA can have its nucleotide sequence altered, these changes are generally not considered true **mutations** in the heritable sense for most organisms. - RNA is typically a temporary molecule, and changes to its sequence are usually not passed down to subsequent generations. *Amino acid sequence of ribonuclease* - An altered **amino acid sequence** in a protein like ribonuclease is a consequence of a **mutation in the DNA**, not the mutation itself. - **Ribonucleases** are enzymes that catalyze the degradation of RNA, and their structure is determined by the **DNA sequence**. *Cell membrane* - The cell membrane is a **lipid bilayer** with embedded proteins that regulates cellular transport and communication. - While its components can be affected by genetic mutations, alterations in the cell membrane itself do not constitute the primary definition of a **mutation**.
Question 8: In which of the following inheritance patterns is father-to-son transmission not observed?
- A. Autosomal dominant inheritance
- B. Autosomal recessive inheritance
- C. Multifactorial inheritance
- D. X-linked recessive inheritance (Correct Answer)
Explanation: ***X-linked recessive inheritance*** - In X-linked inheritance, females have two X chromosomes (XX) and males have one X and one Y chromosome (XY). A father always passes his **Y chromosome** to his son. - He passes his **X chromosome only to his daughters**. Therefore, a father cannot pass an X-linked trait directly to his son. *Autosomal dominant inheritance* - In autosomal dominant inheritance, a disease allele is located on a **non-sex chromosome (autosome)**. - Both males and females can be affected, and **father-to-son transmission is possible** if the father carries the dominant allele on an autosome. *Autosomal recessive inheritance* - This inheritance pattern also involves genes on **autosomes**. - A father can transmit a recessive allele to his son, though the son would only express the trait if he also inherits a recessive allele from his mother. **Father-to-son transmission of the allele is possible**. *Multifactorial inheritance* - This pattern involves the interaction of **multiple genes** and **environmental factors**. - As some of these genes are on autosomes, and environmental factors are independent of sex chromosomes, **father-to-son transmission is observed** for the genetic components.
Question 9: A patient diagnosed with an isolated increase in LDL, with a family history of the same disease in his father and brother, is likely to have a diagnosis of
- A. Abetalipoproteinemia
- B. LDL receptor mutation (Correct Answer)
- C. Familial type III hyperlipoproteinemia
- D. Familial lipoprotein lipase deficiency
Explanation: ***LDL receptor mutation*** - An **isolated increase in LDL** with a strong **family history** (father and brother affected) is highly suggestive of **familial hypercholesterolemia**, which is most commonly caused by mutations in the **LDL receptor gene** [1]. - **LDL receptor mutations** lead to a reduced clearance of LDL from the blood, resulting in elevated LDL levels from birth [1]. *Familial type III hyperlipoproteinemia* - This condition is characterized by elevated levels of both **cholesterol and triglycerides**, specifically involving **remnant lipoproteins** (IDL), not an isolated increase in LDL [2]. - It is often associated with **palmar xanthomas** and **tuberous xanthomas**, which are not mentioned in the patient's presentation. *Abetalipoproteinemia* - This is a rare genetic disorder characterized by the **absence of apolipoprotein B**, leading to very low or undetectable levels of **LDL, VLDL, and chylomicrons**. - Patients typically present with **fat malabsorption, neurologic deficits**, and **retinitis pigmentosa**, which is contrary to an isolated increase in LDL. *Familial lipoprotein lipase deficiency* - This condition primarily causes a marked elevation in **chylomicrons and triglycerides** due to impaired clearance of triglyceride-rich lipoproteins. - It does not present as an isolated increase in LDL and is often associated with **eruptive xanthomas**, **pancreatitis**, and **hepatosplenomegaly**.
Question 10: Wilson's disease has which of the following inheritance?
- A. It is an acquired disease
- B. Autosomal recessive (Correct Answer)
- C. X-linked recessive
- D. Autosomal dominant
Explanation: ***Autosomal recessive*** - Wilson's disease is caused by mutations in the **ATP7B gene**, which codes for a copper-transporting ATPase. - For an individual to develop the disease, they must inherit **two copies of the mutated gene**, one from each parent. *It is an acquired disease* - Wilson's disease is a **genetic disorder**, meaning it is inherited, not acquired through environmental factors or lifestyle [1]. - While symptoms may manifest later in life, the underlying cause is a **predisposing genetic mutation** [1]. *X-linked recessive* - X-linked recessive disorders primarily affect males as they have only one X chromosome; however, Wilson's disease **affects both sexes equally**. - The gene responsible for Wilson's disease, **ATP7B**, is located on **chromosome 13**, an autosome, not on the X chromosome. *Autosomal dominant* - In autosomal dominant inheritance, only **one copy of the mutated gene** is sufficient to cause the disease, and it is usually seen in every generation. - Wilson's disease requires **two mutated copies** of the gene to manifest, and carriers (heterozygotes) are typically asymptomatic.
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