Principles of Medical Genetics Indian Medical PG Practice Questions and MCQs
Practice Indian Medical PG questions for Principles of Medical Genetics. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Principles of Medical Genetics Indian Medical PG Question 1: Pattern of inheritance where mother transmits disease to all children -
- A. Mitochondrial inheritance (Correct Answer)
- B. X-linked recessive
- C. Autosomal dominant
- D. Autosomal recessive
Principles of Medical Genetics Explanation: ***Mitochondrial inheritance***
- Mitochondrial DNA (mtDNA) is exclusively inherited from the **mother**, meaning all children of an affected mother will inherit the mitochondrial disease.
- Fathers do not pass on their mtDNA to their offspring, so an affected father's children will not inherit mitochondrial conditions from him.
*X-linked recessive*
- In X-linked recessive inheritance, sons have a 50% chance of being affected if their mother is a carrier, and daughters have a 50% chance of being carriers.
- It does not guarantee that **all children** will inherit the disease from an affected mother; affected mothers would pass the X-linked gene to all sons (who would be affected) and all daughters (who would be carriers or affected depending on the other X chromosome).
*Autosomal dominant*
- In autosomal dominant inheritance, an affected parent has a 50% chance of passing the allele to **each child**, regardless of sex.
- This pattern means not all children will necessarily inherit the disease, and both sexes are affected equally.
*Autosomal recessive*
- For autosomal recessive diseases, both parents must be carriers or affected for a child to inherit the disease, and even then, there is only a 25% chance for each child to be affected if both parents are carriers.
- This pattern does not result in **all children** inheriting the disease from an affected mother, as it requires contributions from both parents.
Principles of Medical Genetics Indian Medical PG Question 2: Which of the following translocations is not associated with Down syndrome?
- A. t(21;21)
- B. t(14;21)
- C. t(15;21)
- D. t(11;14) (Correct Answer)
Principles of Medical Genetics Explanation: ***t (11: 14)***
- The **t(11;14) translocation** is commonly associated with **mantle cell lymphoma**, a B-cell non-Hodgkin lymphoma, and is not a cause of Down syndrome.
- This translocation leads to the overexpression of the **cyclin D1 gene**, located on chromosome 11, which promotes cell growth and proliferation.
*t (14; 21)*
- This is a common **Robertsonian translocation** involving chromosomes 14 and 21, which results in an extra copy of chromosome 21 material [1].
- Individuals with this translocation can have **Down syndrome** because their cells end up with the equivalent of three copies of chromosome 21 [1].
*t (21; 21)*
- This translocation is another type of **Robertsonian translocation** where two chromosome 21s fuse.
- This specific translocation is rare and results in an extra copy of chromosome 21, leading to **Down syndrome** with a high recurrence risk in offspring.
*t (15: 21)*
- This is a **Robertsonian translocation** involving chromosomes 15 and 21, resulting in an extra copy of chromosome 21 material.
- This translocation is a known cause of **Down syndrome** due to the dosage imbalance of genes on chromosome 21 [1].
**References:**
[1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 169-172.
Principles of Medical Genetics Indian Medical PG Question 3: What is the term for a single mutation in a nucleotide base pair that results in a termination codon?
- A. Missense mutation
- B. Nonsense mutation (Correct Answer)
- C. Termination mutation
- D. Silent mutation
Principles of Medical Genetics Explanation: ***Nonsense mutation***
- A **nonsense mutation** occurs when a single nucleotide base pair change leads to the formation of a **premature stop codon**, which results in a truncated and often non-functional protein.
- The term "nonsense" refers to the fact that the new codon signals an early termination of protein synthesis.
*Missense mutation*
- A **missense mutation** involves a single nucleotide change that results in a codon coding for a **different amino acid**, potentially altering protein function but not necessarily terminating it.
- This type of mutation can have varying effects on protein function, from benign to severe, depending on the amino acid substitution.
*Termination mutation*
- While a nonsense mutation does result in **premature termination**, "termination mutation" is not the standard or most precise scientific term used to describe this specific type of genetic alteration.
- The more accurate and widely accepted terminology is **nonsense mutation** for a change leading to a stop codon.
*Silent mutation*
- A **silent mutation** is a type of point mutation that changes a single nucleotide, but does not change the amino acid sequence of the protein due to the **degeneracy of the genetic code**.
- These mutations have **no observable effect** on the organism's phenotype as the protein produced remains unchanged.
Principles of Medical Genetics Indian Medical PG Question 4: Best method for the detection of mutations with low allele frequency is:
- A. FISH
- B. Droplet digital PCR (Correct Answer)
- C. Sanger sequencing
- D. Nested PCR
Principles of Medical Genetics Explanation: ***Droplet digital PCR***
- **Droplet digital PCR (ddPCR)** offers superior sensitivity for detecting **low allele frequency mutations** by partitioning the sample into thousands of individual reactions.
- This compartmentalization allows for the direct quantification of target DNA molecules without relying on a standard curve, making it highly accurate for rare mutation detection.
*FISH*
- **Fluorescence in situ hybridization (FISH)** primarily detects **chromosomal abnormalities** like translocations, deletions, or amplifications, rather than single-nucleotide variants or small indels with low allele frequencies [2].
- It visualizes genetic changes at a **cytogenetic level** on an intracellular basis, not typically for quantifying rare DNA mutations in a heterogeneous sample.
*Sanger sequencing*
- **Sanger sequencing** is the gold standard for **sequencing individual DNA fragments** but has a detection limit of around 15-20% for allele frequency, making it unsuitable for very low allele frequency mutations [1].
- It struggles to reliably detect minor alleles when they are present in a small proportion of the total DNA pool.
*Nested PCR*
- **Nested PCR** increases the sensitivity and specificity of amplification by using two sets of primers in a sequential manner but does not inherently provide the **quantification capability** or the same level of **low allele frequency detection** as ddPCR processes.
- While sensitive for detecting target sequences, it is not designed for precise quantification of rare mutations in a background of wild-type sequences.
**References:**
[1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 185.
[2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 185-186.
Principles of Medical Genetics Indian Medical PG Question 5: What is the pattern of inheritance in neural tube defects?
- A. Multifactorial inheritance (Correct Answer)
- B. Autosomal recessive
- C. X-linked dominant
- D. Autosomal dominant
- E. X-linked recessive
Principles of Medical Genetics Explanation: ***Multifactorial inheritance***
- Neural tube defects (NTDs) are a classic example of **multifactorial inheritance**, meaning they result from a combination of **genetic predispositions** and **environmental factors**.
- Risk is influenced by multiple genes, and environmental factors like **folate deficiency** play a significant role.
*Autosomal recessive*
- This pattern involves two copies of an altered gene to cause disease, typically resulting in a **25% recurrence risk** for siblings.
- While some rare isolated NTDs might have an autosomal recessive component, the general presentation of NTDs does not fit this classic mendelian pattern.
*X-linked dominant*
- Involves genes on the **X chromosome** where one altered copy is sufficient to cause disease; affected fathers pass it to all daughters, but no sons.
- This inheritance pattern is very rare for NTDs and would present with a distinct sex-linked pattern of affected individuals.
*Autosomal dominant*
- Requires only one copy of an altered gene to cause disease, leading to a **50% recurrence risk** for offspring.
- While some syndromes associated with NTDs can be autosomal dominant, the primary mechanism for isolated NTDs is not solely due to a single dominant gene.
*X-linked recessive*
- Involves genes on the **X chromosome** where two altered copies are needed in females, but only one in males; typically affects males predominantly.
- This inheritance pattern does not account for the observed familial clustering and environmental contribution seen in NTDs.
Principles of Medical Genetics Indian Medical PG Question 6: Gluten sensitive enteropathy is strongly associated with:-
- A. HLA-DQ2 (Correct Answer)
- B. HLA-DQ3
- C. Blood group B
- D. HLA-DR4
Principles of Medical Genetics Explanation: ### HLA-DQ2
- **HLA-DQ2** is the most significant **genetic risk factor** for **celiac disease** (gluten-sensitive enteropathy), present in about 90-95% of patients [1].
- Its presence is necessary, though not sufficient, for the development of the disease, playing a crucial role in immune response to **gluten peptides** [1].
### HLA-DQ3
- While other HLA-DQ alleles exist, **HLA-DQ3** is not primarily associated with celiac disease.
- The dominant susceptibility alleles are **HLA-DQ2** and, to a lesser extent, **HLA-DQ8** [1].
### Blood group B
- There is **no established strong association** between **blood group B** and the development of celiac disease.
- Blood groups are primarily related to red blood cell antigens, not directly to autoimmune conditions like celiac disease.
### HLA-DR4
- **HLA-DR4** is mainly associated with other autoimmune diseases, particularly **rheumatoid arthritis**, and is not a primary genetic marker for celiac disease.
- Although it's part of the MHC class II locus, its specific alleles like **HLA-DQ2** and **HLA-DQ8** are more relevant for celiac disease [1].
Principles of Medical Genetics Indian Medical PG Question 7: 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
Principles of Medical Genetics 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.
Principles of Medical Genetics Indian Medical PG Question 8: Genetic disorder predisposing patients to develop Berry aneurysm includes all EXCEPT:
- A. Marfan’s syndrome
- B. Adult polycystic kidney
- C. Neurofibromatosis Type II (Correct Answer)
- D. Fibromuscular dysplasia
Principles of Medical Genetics Explanation: ***Neurofibrofomatosis Type II***
- This condition is primarily associated with **central nervous system tumors** like **vestibular schwannomas** and **meningiomas**, not Berry aneurysms [2].
- While it affects the nervous system, its vascular manifestations are typically different from those predisposing to aneurysms.
*Marfan’s syndrome*
- Patients with Marfan's syndrome have **fragile connective tissue** due to a defect in **fibrillin-1**, which can weaken arterial walls.
- This weakness increases the risk of **aortic aneurysms** and dissections, and can also predispose to intracranial aneurysms like Berry aneurysms.
*Adult polycystic kidney*
- This **autosomal dominant** disorder is characterized by the formation of **cysts in the kidneys**, but also has systemic manifestations [1].
- There is a well-established association between **autosomal dominant polycystic kidney disease (ADPKD)** and an increased incidence of **Berry aneurysms**.
*Fibromuscular dysplasia*
- This condition involves **abnormal cellular development** in the **arterial walls**, leading to areas of narrowing and enlargement.
- It commonly affects the **renal arteries** and **carotid arteries**, and is also a known risk factor for the development of **intracranial aneurysms**, including Berry aneurysms.
Principles of Medical Genetics Indian Medical PG Question 9: Which of the following conditions is associated with ectopia lentis?
- A. Homocystinuria (Correct Answer)
- B. Alport syndrome
- C. Lowe syndrome
- D. Sulphite oxidase deficiency
Principles of Medical Genetics Explanation: ***Homocystinuria***
- **Ectopia lentis** (lens dislocation) is a common and characteristic ocular manifestation of homocystinuria.
- The lens typically dislocates **downward and inward**, differentiating it from Marfan syndrome.
*Alport syndrome*
- Characterized by **glomerulonephritis**, **sensorineural hearing loss**, and ocular abnormalities.
- Ocular manifestations include **anterior lenticonus** (which can be mistaken for ectopia lentis in some descriptions), posterior polymorphous corneal dystrophy, and retinal flecks, but not classic ectopia lentis.
*Lowe syndrome*
- Also known as oculocerebrorenal syndrome of Lowe, it primarily affects the **eyes, brain, and kidneys**.
- Ocular features include **congenital cataracts** and glaucoma, but not ectopia lentis.
*Sulphite oxidase deficiency*
- This is a rare metabolic disorder affecting the metabolism of sulfur-containing amino acids, leading to severe neurological symptoms.
- While it can manifest with **cataracts** and **lens subluxation** in some cases, ectopia lentis is more characteristically associated with homocystinuria, and the overall clinical picture of sulphite oxidase deficiency is dominated by severe neurological impairment.
Principles of Medical Genetics Indian Medical PG Question 10: A patient presents with headache, confusion, and a diagnosis of a brain tumor. The family history reveals brain and kidney tumors. What is the most likely diagnosis?
- A. Neurofibromatosis
- B. Li-Fraumeni syndrome
- C. VHL syndrome (Correct Answer)
- D. Churg-Strauss syndrome
Principles of Medical Genetics Explanation: ***VHL syndrome***
- **Von Hippel-Lindau (VHL) syndrome** is an inherited disorder characterized by the growth of tumors and cysts in various parts of the body, including the **brain (hemangioblastomas)** and **kidneys (renal cell carcinoma)**.
- The presentation of a brain tumor, kidney tumors, and a positive family history for both organs strongly points to VHL syndrome.
*Neurofibromatosis*
- **Neurofibromatosis (NF)** typically presents with **cafe-au-lait spots**, neurofibromas, optic gliomas, and Lisch nodules.
- While it involves brain tumors, kidney tumors are not a primary feature of NF.
*Li-Fraumeni syndrome*
- **Li-Fraumeni syndrome** is associated with an increased risk of various cancers, including **sarcomas**, **breast cancer**, **adrenocortical carcinomas**, and **leukemia**.
- While brain tumors can occur, the specific combination of brain and kidney tumors with a clear family history is less characteristic of Li-Fraumeni than VHL syndrome.
*Churg-Strauss syndrome*
- **Churg-Strauss syndrome (Eosinophilic Granulomatosis with Polyangiitis)** is a systemic vasculitis characterized by **asthma**, **eosinophilia**, and **granulomatous inflammation**.
- It does not involve the development of brain or kidney tumors.
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