Genetics and Disease Practice Questions

Q: The following pedigree represents which of the following genetic disorders?

Osteogenesis imperfecta. ***Osteogenesis imperfecta*** - Shows **autosomal dominant inheritance** pattern with **vertical transmission** - affected individuals in every generation passing the condition to approximately **50% of their offspring**. - **Type I osteogenesis imperfecta** is the most common form with this inheritance pattern, caused by mutations in **COL1A1** or **COL1A2** genes affecting collagen production. *Wilson's disease* - Follows **autosomal recessive inheritance** pattern, which would show **horizontal transmission** with unaffected parents having affected children. - Caused by mutations in the **ATP7B gene**, leading to copper accumulation, and would not demonstrate the vertical inheritance pattern seen in this pedigree. *Alkaptonuria* - Exhibits **autosomal recessive inheritance**, characterized by **consanguineous marriages** and affected siblings from unaffected parents. - Results from **homogentisic acid oxidase deficiency**, causing dark urine and would not show the dominant inheritance pattern observed. *Cystic fibrosis* - Demonstrates **autosomal recessive inheritance** with **horizontal transmission** pattern, typically affecting siblings rather than successive generations. - Caused by **CFTR gene mutations** and would require both parents to be carriers, not the dominant pattern shown in this pedigree.

Q: Which of the following statements about hemochromatosis is false?

Leads to iron deposits in the testis. The correct answer is **C**. While Hereditary Hemochromatosis (HH) is a multi-system disorder of iron overload, the endocrine dysfunction involving the gonads is **not** primarily due to direct iron deposition in the testes [1]. Instead, it is caused by iron deposition in the **anterior pituitary gland**, leading to selective gonadotropin deficiency (Hypogonadotropic Hypogonadism) [1]. This results in secondary testicular atrophy, decreased libido, and impotence. **Analysis of other options:** * **Option A:** True. Most cases (approx. 85-90%) of classic HH are caused by a mutation in the **HFE gene** (most commonly the C282Y mutation) on Chromosome 6 [1]. * **Option B:** True. HH is inherited in an **autosomal recessive** pattern with variable penetrance [1]. * **Option D:** True. **Secondary hemochromatosis** occurs due to ineffective erythropoiesis (as seen in **Thalassemias** or Sideroblastic anemia) and chronic blood transfusions, leading to systemic iron overload despite a normal HFE gene. **NEET-PG High-Yield Pearls:** * **Classic Triad (Bronze Diabetes):** Cirrhosis, Diabetes Mellitus, and Skin Hyperpigmentation (occurs in late stages) [1]. * **Most Common Joint Involved:** Second and third metacarpophalangeal (MCP) joints (hook-like osteophytes). * **Cardiac Involvement:** Typically presents as Restrictive Cardiomyopathy (early) or Dilated Cardiomyopathy (late). * **Diagnosis:** Best initial screening test is **Transferrin Saturation** (>45%); Gold standard for HFE-HH is **Genetic Testing** [2]. * **Treatment:** Therapeutic phlebotomy is the mainstay of management [2].

Q: Males who are sexually underdeveloped with rudimentary testes and prostate glands, sparse pubic and facial hair, long arms and legs and large hands and feet are likely to have which chromosome complement?

47, XXY. The clinical presentation described—hypogonadism (rudimentary testes/prostate), lack of secondary sexual characteristics (sparse hair), and **eunuchoid body habitus** (long extremities)—is the classic triad of **Klinefelter Syndrome** [1]. **1. Why 47, XXY is correct:** Klinefelter Syndrome is the most common cause of congenital hypogonadism in males [2]. The presence of an extra X chromosome leads to testicular dysgenesis [2]. Specifically, the destruction of seminiferous tubules results in low testosterone and elevated gonadotropins (Hypergonadotropic Hypogonadism) [1]. The increased height and long limbs are attributed to the overexpression of the **SHOX gene** (located on the X chromosome), which remains active and delays epiphyseal closure. **2. Analysis of Incorrect Options:** * **45, XYY (Jacob’s Syndrome):** These individuals are usually phenotypically normal, very tall, and may have cystic acne or behavioral issues, but they do not have underdeveloped genitalia or sparse hair. * **46, XY:** This is the normal male karyotype. * **45, X0 (Turner Syndrome):** This presents in females with short stature, webbed neck, and streak ovaries [3]. It is the polar opposite of the tall, male phenotype described. **3. High-Yield Clinical Pearls for NEET-PG:** * **Lab Findings:** ↓ Testosterone, ↑ LH, ↑ FSH, and ↑ Estradiol (leading to **Gynecomastia**) [1]. * **Histology:** Fibrosis and hyalinization of seminiferous tubules with **Leydig cell hyperplasia** [1]. * **Key Risk:** These patients have a significantly higher risk of **Breast Cancer** (20x) and **Extragonadal Germ Cell Tumors** [4]. * **Mental Health:** Often associated with mild intellectual disability or executive dysfunction [1].

Q: What is the incidence of Down's syndrome directly proportional to?

Maternal age. The correct answer is **Maternal Age**. Down’s syndrome (Trisomy 21) is primarily caused by **meiotic non-disjunction**, where chromosomes fail to separate properly during oogenesis. As a woman ages, the primary oocytes (which have been arrested in Prophase I since birth) undergo "biological aging." This leads to a breakdown in the spindle apparatus and cohesive proteins, significantly increasing the risk of chromosomal errors. While the risk is approximately 1 in 1,500 at age 20, it rises sharply to 1 in 100 by age 40 and 1 in 25 by age 45. **Analysis of Incorrect Options:** * **Parity:** The number of previous pregnancies does not influence chromosomal non-disjunction; a first-time mother at age 40 has the same risk as a multiparous woman of the same age. * **Consanguinity:** This increases the risk of **autosomal recessive** disorders (e.g., Thalassemia, Wilson’s disease) by bringing together rare recessive alleles, but it does not cause numerical chromosomal aberrations like Trisomy 21. * **Mutations:** While Down’s syndrome is a genetic abnormality, it is typically a **cytogenetic error** (aneuploidy) rather than a point mutation or a specific gene defect. **High-Yield Clinical Pearls for NEET-PG:** * **Most common cause:** Meiotic non-disjunction (95% of cases), most often occurring during Maternal Meiosis I. * **Robertsonian Translocation:** Accounts for ~4% of cases; unlike non-disjunction, this type is **not** related to maternal age and carries a high recurrence risk if a parent is a carrier. * **Screening:** The "Quadruple Screen" (done at 15-20 weeks) typically shows **Low AFP, Low uE3, High hCG, and High Inhibin-A.** * **Ultrasound marker:** Increased Nuchal Translucency (NT) in the first trimester.

Q: Turner's syndrome is characterized by which of the following findings, except?

Tall stature. **Explanation:** Turner’s syndrome (45,XO) is the most common sex chromosome abnormality in females [1], [5]. The hallmark of this condition is **short stature**, not tall stature [1]. This is primarily due to the haploinsufficiency of the **SHOX gene** (Short Stature Homeobox gene) located on the distal part of the X chromosome. **Why "Tall Stature" is the correct answer (the exception):** Patients with Turner’s syndrome typically have a height below the 3rd percentile. Growth failure is often the most consistent clinical feature. In contrast, tall stature is associated with conditions like Marfan syndrome, Klinefelter syndrome (47,XXY), or XYY syndrome [2]. **Analysis of incorrect options:** * **Renal malformations:** Approximately 30-50% of patients have renal anomalies, the most classic being the **Horseshoe kidney**. Other findings include duplication of the collecting system. * **Primary amenorrhea:** This occurs due to **gonadal dysgenesis** (streak ovaries) [4]. The accelerated loss of oocytes leads to premature ovarian failure, resulting in hypergonadotropic hypogonadism [3]. * **Lymphedema:** Congenital lymphedema of the hands and feet is a common neonatal presentation [5]. It is caused by lymphatic hypoplasia and often results in a "webbed neck" (cystic hygroma) later in life. **High-Yield Clinical Pearls for NEET-PG:** * **Cardiac:** Bicuspid aortic valve (most common) and Coarctation of the aorta. * **Dermatological:** Multiple pigmented nevi and high-arched palate. * **Endocrine:** Increased risk of Hashimoto’s thyroiditis and Celiac disease. * **Karyotype:** 45,XO is the most common, but mosaicism (45,X/46,XX) can present with milder features and secondary amenorrhea [5].

Q: What is the cause of thick pancreatic secretions in cystic fibrosis?

Defect in chloride channel leading to water reabsorption. **Explanation:** The fundamental defect in Cystic Fibrosis (CF) is a mutation in the **CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene**, which encodes a cAMP-regulated chloride channel. **Why Option C is Correct:** In the pancreas and respiratory tract, the CFTR protein normally pumps chloride ions *out* of the epithelial cells into the lumen. This creates an osmotic gradient that draws water into the secretions, keeping them hydrated and fluid. In CF, the defective channel prevents chloride secretion. Consequently, there is a compensatory **increase in sodium and water reabsorption** from the lumen into the cells to maintain isotonicity. This dehydration of the luminal surface leads to the formation of viscid, inspissated (thick) secretions that obstruct pancreatic ducts, leading to exocrine insufficiency and fibrosis. **Why Other Options are Incorrect:** * **Option A & B:** While mucin clearance is impaired, the primary pathology is not an overproduction of mucin or a simple mechanical failure of the epithelium; it is the secondary result of the underlying electrolyte and water imbalance. * **Option D:** The primary defect is in the **chloride channel**, not the sodium channel (ENaC). While sodium reabsorption is increased, it is a secondary physiological response to the chloride transport failure. **High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** Most common mutation is **ΔF508** (Class II defect: protein misfolding and trafficking failure). * **Sweat Gland Paradox:** Unlike the pancreas, in sweat glands, CFTR normally *reabsorbs* chloride. Therefore, CF patients have **high sweat chloride** (>60 mEq/L), which is the gold standard for diagnosis. * **Meconium Ileus:** The earliest clinical manifestation of CF in neonates. * **Infertility:** 95% of males are infertile due to **Congenital Bilateral Absence of Vas Deferens (CBAVD)**.

Q: What is the most common mutated gene in primary hemochromatosis?

HFE gene. **Primary (Hereditary) Hemochromatosis** is an autosomal recessive disorder characterized by excessive intestinal iron absorption leading to systemic iron overload [2]. **Why HFE is the Correct Answer:** The **HFE gene** (located on Chromosome 6) is the most common cause of primary hemochromatosis, accounting for over 80-90% of cases in clinical practice [2]. The most frequent mutation is the **C282Y** substitution (cysteine to tyrosine), followed by the H63D mutation [1]. The HFE protein normally regulates the interaction between the transferrin receptor and hepcidin; its mutation leads to inappropriately low hepcidin levels, causing uncontrolled iron entry into the plasma. **Why Other Options are Incorrect:** * **Transferrin receptor 2 (TfR2):** Mutations here cause Type 3 Hereditary Hemochromatosis. It is much rarer than HFE-related disease. * **Ferroportin 1 (SLC40A1):** Mutations lead to Type 4 Hemochromatosis (Ferroportin disease). Unlike other types, this often presents with high ferritin but low-to-normal transferrin saturation initially. * **Hepcidin (HAMP):** Mutations in the HAMP gene cause Type 2B Juvenile Hemochromatosis, a rare and severe form that presents in the second decade of life with early cardiac and endocrine failure. **High-Yield Clinical Pearls for NEET-PG:** * **Classic Triad (Bronze Diabetes):** Cirrhosis, Diabetes Mellitus, and Skin Hyperpigmentation (occurs late) [2]. * **Screening Test of Choice:** Transferrin Saturation (>45% is highly suggestive). * **Confirmatory Test:** HFE Gene Analysis (Genetic testing) [1]. * **MRI Findings:** "Signal dropout" on T2-weighted images due to iron deposition in the liver [1]. * **Treatment:** Therapeutic Phlebotomy is the mainstay of management [1]. * **Arthropathy:** Characteristically involves the 2nd and 3rd metacarpophalangeal (MCP) joints with "hook-like" osteophytes.

Q: Down's syndrome is characterized by which chromosomal abnormality?

Trisomy. **Explanation:** **Down Syndrome (Trisomy 21)** is the most common chromosomal disorder and a frequent topic in NEET-PG. The correct answer is **Trisomy** because the condition is characterized by the presence of an extra copy of chromosome 21 (47, XX/XY, +21). This occurs primarily due to **meiotic non-disjunction** (95% of cases), most commonly during maternal meiosis I. **Analysis of Options:** * **Triploidy (A):** This refers to a complete extra set of chromosomes (3n = 69). It is usually incompatible with life and results in early spontaneous abortion. * **Monosomy (B):** This is the absence of one member of a pair of chromosomes (e.g., Turner Syndrome, 45, XO). Autosomal monosomies are lethal. * **Aneuploidy (D):** While Down Syndrome *is* a type of aneuploidy (an abnormal number of chromosomes), **Trisomy** is the more specific and clinically accurate description. In competitive exams, always choose the most specific term provided. **High-Yield Clinical Pearls for NEET-PG:** * **Risk Factor:** Advanced maternal age (>35 years) is the strongest risk factor for non-disjunction. * **Genetics:** 95% are due to Trisomy 21, 3-4% due to **Robertsonian Translocation** (usually t(14;21)), and 1-2% due to **Mosaicism**. * **Screening:** First-trimester screening shows **increased Nuchal Translucency**, decreased PAPP-A, and increased β-hCG. * **Associations:** Endocardial cushion defects (AVSD), Duodenal atresia ("Double bubble" sign), Early-onset Alzheimer’s, and increased risk of ALL/AML (M7 subtype).

Question 1

The following pedigree represents which of the following genetic disorders?

Accepted Answer

Osteogenesis imperfecta

Answer

Wilson’s disease

Answer

Alkaptonuria

Answer

Cystic fibrosis

Question 2

Which of the following statements is TRUE regarding Duchenne muscular dystrophy?

Accepted Answer

There is a universal increase in creatine kinase.

Answer

It is autosomal dominant.

Answer

It has an onset in the second decade of life.

Answer

Cardiac muscle fibers are normal.

Question 3

Which of the following statements about hemochromatosis is false?

Accepted Answer

Leads to iron deposits in the testis

Answer

Caused by HFE gene mutation

Answer

Inherited in an autosomal recessive pattern

Answer

Secondary hemochromatosis can result from thalassemias

Question 4

Males who are sexually underdeveloped with rudimentary testes and prostate glands, sparse pubic and facial hair, long arms and legs and large hands and feet are likely to have which chromosome complement?

Accepted Answer

47, XXY

Answer

45, XYY

Answer

46, XY

Answer

45, X0

Question 5

A family consists of a husband, wife, and children. The wife's father has Huntington's chorea. Which statement is true regarding this genetic condition?

Accepted Answer

If the wife does not develop the disease by age 50, her children will not be affected.

Answer

The chance of a child inheriting the disease is 1:4.

Answer

The disease can manifest up to the age of 50.

Answer

Huntington's chorea is caused by a point mutation in a gene.

Question 6

What is the incidence of Down's syndrome directly proportional to?

Accepted Answer

Maternal age

Answer

Parity

Answer

Consanguinity

Answer

Mutations

Question 7

Turner's syndrome is characterized by which of the following findings, except?

Accepted Answer

Tall stature

Answer

Renal malformations

Answer

Primary amenorrhea

Answer

Lymphedema

Question 8

What is the cause of thick pancreatic secretions in cystic fibrosis?

Accepted Answer

Defect in chloride channel leading to water reabsorption

Answer

Overproduction of mucin

Answer

Failure to clear mucin due to epithelial dysfunction

Answer

Defect in sodium channel leading to water reabsorption

Question 9

What is the most common mutated gene in primary hemochromatosis?

Accepted Answer

HFE gene

Answer

Transferrin receptor 2

Answer

Ferroportin 1

Answer

Hepcidin

Question 10

Down's syndrome is characterized by which chromosomal abnormality?

Accepted Answer

Trisomy

Answer

Triploidy

Answer

Monosomy

Answer

Aneuploidy

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?