Molecular Basis of Genetic 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?
Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
An affected male does not have affected children but an affected female always has affected children. Type of inheritance?
Examine this pedigree chart carefully. What type of transmission does it depict?
Syndrome which is characterized by 2X chromosomes and 1Y chromosome is:
Increasing severity of intellectual disability of male members over generations is a result of ?
What is the type of inheritance in MELAS?
Restriction fragment length polymorphism is used for:
Phenotypic expression of a gene depending on the parent of origin is referred to as:
Dent's disease is characterized by all except:
Molecular Basis of Genetic 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: Prader-Willi syndrome and Angelman syndrome are examples of what genetic phenomenon?
- A. Gene Knockout
- B. Impaired DNA repair
- C. Genomic Imprinting (Correct Answer)
- D. RNA interference
Explanation: ***Genomic Imprinting*** - **Genomic imprinting** is an epigenetic phenomenon where certain genes are expressed in a **parent-of-origin-specific manner**. - In Prader-Willi syndrome, the disease results from the loss of function of specific genes on chromosome 15 (15q11-q13) inherited from the father, while Angelman syndrome results from the loss of function of a different gene (UBE3A) in the same region, but inherited from the mother. *RNA interference* - **RNA interference** is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules. - This process is not directly responsible for the parent-of-origin-specific expression patterns observed in these syndromes. *Gene Knockout* - A **gene knockout** is a genetic technique in which an organism's genes are made inoperative. - While it involves modifying gene function, it does not explain the differential expression based on parental origin. *Impaired DNA repair* - **Impaired DNA repair** refers to defects in the mechanisms that correct DNA damage. - This can lead to increased mutations and conditions like cancer, but it is not the underlying mechanism for Prader-Willi or Angelman syndromes.
Question 3: An affected male does not have affected children but an affected female always has affected children. Type of inheritance?
- A. Autosomal recessive
- B. Mitochondrial (Correct Answer)
- C. X linked recessive
- D. X linked dominant
Explanation: ***Correct Option: Mitochondrial*** - This pattern describes **mitochondrial inheritance**, where all children of an **affected mother** inherit the condition because mitochondria are exclusively inherited from the ovum (maternal inheritance). - An **affected father** cannot pass on the condition to his children, as sperm contribute only nuclear DNA and essentially no mitochondria. - This is the **only inheritance pattern** where an affected male has no affected children while an affected female has all children affected. *Incorrect Option: Autosomal recessive* - This pattern would typically show affected individuals having unaffected parents (who are carriers) and both males and females being affected in equal proportions. - It does not explain the complete absence of transmission from an affected father or universal transmission from an affected mother. - An affected individual could have unaffected children if their partner is not a carrier. *Incorrect Option: X linked recessive* - In **X-linked recessive inheritance**, affected males cannot pass the trait to their sons, but all their daughters would be carriers (not affected). - An affected mother would pass the trait to all her sons (affected) and make all her daughters carriers (not affected), which does not match the described pattern of all children being affected. *Incorrect Option: X linked dominant* - In **X-linked dominant inheritance**, an affected father passes the trait to all his daughters but none of his sons (contradicts "no affected children"). - An affected mother has a 50% chance of passing the trait to **each child**, which is inconsistent with all children of an affected female being affected.
Question 4: Examine this pedigree chart carefully. What type of transmission does it depict?
- A. AR Inheritance
- B. AD Inheritance
- C. Holandric Inheritance (Correct Answer)
- D. X-Linked Recessive
Explanation: ***Holandric Inheritance*** - **Holandric inheritance** (Y-linked) shows the trait appearing only in **males** and being transmitted from **father to all his sons**. - The pedigree demonstrates classic **father-to-son transmission** pattern where affected fathers (I-1 and II-3) pass the trait to all their male offspring. *AR Inheritance* - **Autosomal recessive** traits typically **skip generations** and affect both males and females equally. - Affected individuals usually have **unaffected carrier parents**, which is not consistently observed in this pedigree. *AD Inheritance* - **Autosomal dominant** traits affect both sexes equally and show **vertical transmission** through generations. - An affected father would pass the trait to approximately **50% of all children** regardless of sex, not exclusively to sons. *X-Linked Recessive* - **X-linked recessive** inheritance affects males predominantly, but **affected fathers cannot pass** the trait to their sons. - Sons receive the **Y chromosome from father** and X chromosome from mother, making father-to-son transmission impossible.
Question 5: Syndrome which is characterized by 2X chromosomes and 1Y chromosome is:
- A. Turner syndrome
- B. Marfan syndrome
- C. Down syndrome
- D. Klinefelter syndrome (Correct Answer)
Explanation: ***Klinefelter syndrome*** - This syndrome is characterized by a **47, XXY karyotype**, meaning individuals have **two X chromosomes** and one Y chromosome [1]. - It affects males, leading to features such as **small testes**, **infertility**, gynecomastia, and often taller stature [1], [3]. *Turner syndrome* - This syndrome is characterized by a **45, X karyotype**, meaning individuals have only **one X chromosome** and no second sex chromosome [2]. - It affects females, leading to features like **short stature**, a **webbed neck**, and ovarian dysgenesis [2]. *Marfan syndrome* - This is an **autosomal dominant genetic disorder** affecting connective tissue, caused by mutations in the **FBN1 gene**. - It is characterized by **tall stature**, long limbs (arachnodactyly), **cardiovascular abnormalities** (e.g., aortic dissection), and ocular problems (e.g., lens dislocation). *Down syndrome* - This syndrome is caused by **trisomy 21**, meaning individuals have an **extra copy of chromosome 21**. - It is characterized by specific **facial features**, intellectual disability, and an increased risk of certain medical conditions like congenital heart defects.
Question 6: Increasing severity of intellectual disability of male members over generations is a result of ?
- A. Y linked disorder
- B. Frameshift mutation
- C. Trinucleotide repeat mutation (Correct Answer)
- D. Mitochondrial DNA mutation
Explanation: ***Trinucleotide repeat mutation*** - This phenomenon, known as **anticipation**, is characteristic of disorders caused by trinucleotide repeat expansions like **Fragile X syndrome**, where the number of repeats increases in successive generations, leading to earlier onset and more severe symptoms. - The expansion of these repeats often occurs during **meiosis**, particularly **oogenesis** for Fragile X, contributing to the increasing severity observed in offspring. *Y linked disorder* - Y-linked disorders affect only males and are passed from father to son, but they do not typically show increasing severity over generations or the phenomenon of anticipation. - Their inheritance pattern is straightforward and generally consistent across generations, without progressive phenotypic changes. *Frameshift mutation* - A **frameshift mutation** involves the insertion or deletion of nucleotides that are not multiples of three, leading to a shift in the reading frame and an altered protein sequence. - While they can cause severe genetic disorders, **frameshift mutations** do not typically explain the observed increase in severity across generations (anticipation). *Mitochondrial DNA mutation* - Mitochondria are inherited exclusively from the mother, and mutations in **mitochondrial DNA** can cause a range of disorders affecting energy production. - While these disorders can vary in severity due to **heteroplasmy**, they do not typically show a pattern of increasing severity in successive generations due to an expanding repeat sequence.
Question 7: What is the type of inheritance in MELAS?
- A. X-linked Recessive
- B. Autosomal Recessive
- C. Mitochondrial (Correct Answer)
- D. X-linked Dominant
Explanation: ***Mitochondrial*** - **MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes)** is caused by mutations in **mitochondrial DNA**. - **Mitochondrial inheritance** shows **maternal transmission** - the disease is passed from mothers to all of their children (both sons and daughters), but **only daughters can transmit it to the next generation** as sons do not pass on mitochondrial DNA. - This occurs because mitochondria are inherited exclusively from the egg (maternal), not from sperm. *X-linked Recessive* - **X-linked recessive disorders** primarily affect males, as they only have one X chromosome. - The disease is typically transmitted by carrier mothers to their sons, which is not characteristic of MELAS. *Autosomal Recessive* - In **autosomal recessive inheritance**, an individual must inherit two copies of the mutated gene (one from each parent) to be affected. - This pattern of inheritance does not explain the strict maternal transmission observed in MELAS. *X-linked Dominant* - **X-linked dominant disorders** can affect both males and females, but females are often more mildly affected. - All daughters of an affected father will inherit the condition, which differs from the maternal-only inheritance pattern of MELAS.
Question 8: Restriction fragment length polymorphism is used for:
- A. Detection of gene mutations
- B. Genetic mapping and identification (Correct Answer)
- C. Paternity testing
- D. Forensic analysis
Explanation: ***Genetic mapping and identification*** - **Restriction fragment length polymorphism (RFLP)** exploits variations in DNA sequences that create or abolish **restriction enzyme recognition sites**, leading to fragments of different lengths. - These polymorphic fragments serve as **genetic markers** to map genes on chromosomes and identify specific genes or genetic regions. *Detection of gene mutations* - While RFLP can detect some mutations by altering restriction sites, it is not the primary or most efficient method for general **gene mutation detection**. - Techniques like **DNA sequencing** or **PCR-based assays** are typically more sensitive and comprehensive for direct mutation analysis. *Paternity testing* - RFLP was historically used for **paternity testing** by comparing inheritance patterns of polymorphic markers between child and alleged father. - However, it has largely been replaced by more advanced and faster methods like **short tandem repeat (STR) analysis** due to higher discriminatory power and lower DNA requirements. *Forensic analysis* - Similar to paternity testing, RFLP was an early technique employed in **forensic analysis** for DNA fingerprinting to identify individuals. - Modern forensic DNA analysis predominantly uses **STR profiling**, which offers greater resolution, speed, and requires smaller, less degraded samples.
Question 9: Phenotypic expression of a gene depending on the parent of origin is referred to as:
- A. Genomic imprinting (parent-of-origin gene expression) (Correct Answer)
- B. Mosaic genetic variation
- C. Nonpenetrance of genotype
- D. Genetic anticipation
Explanation: ***Genomic imprinting (parent-of-origin gene expression)*** - **Genomic imprinting** is an epigenetic phenomenon where gene expression is dependent on whether the gene was inherited from the mother or the father. - This results in monoallelic expression of specific genes, with only one copy (maternal or paternal) being active. *Mosaic genetic variation* - **Mosaicism** refers to the presence of two or more populations of genetically different cells in one individual, all derived from a single zygote. - This typically arises from a somatic mutation during development, not from differential expression based on parental origin. *Nonpenetrance of genotype* - **Nonpenetrance** occurs when individuals carrying a disease-causing genotype do not express the associated phenotype. - This concept relates to the presence or absence of a phenotype, not the differential expression based on parental origin. *Genetic anticipation* - **Genetic anticipation** is the phenomenon where the symptoms of a genetic disorder become more severe and/or appear at an earlier age in successive generations. - This is commonly observed in disorders caused by expansions of trinucleotide repeats, such as Huntington's disease, and is distinct from parent-of-origin gene expression.
Question 10: Dent's disease is characterized by all except:
- A. Nephrolithiasis
- B. Defect in limb of Loop of Henle (Correct Answer)
- C. Males are affected
- D. Chloride channel defect
Explanation: Dent's disease is characterized by all except: ***Defect in limb of Loop of Henle*** - Dent's disease is primarily a **proximal tubule dysfunction** characterized by low molecular weight proteinuria, hypercalciuria, and nephrocalcinosis, not a defect in the limb of the Loop of Henle. - The disease involves mutations in the *CLC-5* gene, which encodes a **chloride channel** located in the proximal tubule and thick ascending limb, but the dominant pathology stems from proximal tubule dysfunction. *Chloride channel defect* - Dent's disease is indeed caused by mutations in the **CLC-5 chloride channel**, which is critical for endosomal acidification and protein reabsorption in the renal tubules. - The defective chloride channel leads to impaired intracellular trafficking and function of other transporters, predominantly in the proximal tubule. *Males are affected* - Dent's disease is an **X-linked recessive disorder**, meaning that males are predominantly affected because they only have one X chromosome. - Females who are carriers typically exhibit milder symptoms or are asymptomatic due to having a second functional X chromosome. *Nephrolithiasis* - **Hypercalciuria**, a hallmark of Dent's disease, leads to an increased risk of calcium stone formation and deposition in the kidneys. [1] - This often results in recurrent **nephrolithiasis** and progressive chronic kidney disease. [2]
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