**Core Concept**
Retinoblastoma is a malignant tumor of the retina that arises due to mutations in the RB1 gene, a tumor suppressor gene that plays a crucial role in regulating the cell cycle. The RB1 gene is responsible for maintaining the integrity of the cell cycle by controlling the transition from the G1 phase to the S phase.

**Why the Correct Answer is Right**
The RB1 gene is a critical regulator of cell cycle progression, and its inactivation leads to uncontrolled cell proliferation. Mutations in both alleles of the RB1 gene are necessary for the development of retinoblastoma, making it a classic example of a tumor suppressor gene. Familial retinoblastoma is inherited in an autosomal dominant pattern, meaning that a single mutated allele is sufficient to increase the risk of developing the disease. In contrast, the correct answer regarding the chromosomal location of the RB1 gene is incorrect.

**Why Each Wrong Option is Incorrect**
**Option A:** The statement that Rb genes play a major role in cell cycle regulation is true. The RB1 gene is a critical regulator of cell cycle progression, and its inactivation leads to uncontrolled cell proliferation.

**Option B:** The statement that retinoblastoma requires deletion of both Rb genes is true. Mutations in both alleles of the RB1 gene are necessary for the development of retinoblastoma.

**Option C:** The statement that familial variant is autosomal dominant in inheritance is true. Familial retinoblastoma is inherited in an autosomal dominant pattern, meaning that a single mutated allele is sufficient to increase the risk of developing the disease.

**Option D:** The statement that Rb gene is on chromosome 14p13 is incorrect. The RB1 gene is actually located on chromosome 13q14.2.

**Clinical Pearl / High-Yield Fact**
Retinoblastoma is a classic example of a tumor suppressor gene, highlighting the importance of maintaining the integrity of the cell cycle. The RB1 gene is a critical regulator of cell cycle progression, and its inactivation leads to uncontrolled cell proliferation.

**Correct Answer:**
✓ Correct Answer: D. Rb gene is on chromosome 14p13