Explain the relationship between genes, proteins and phenotype with respect to the: • TYR gene, tyrosinase and albinism • HBB gene, haemoglobin and sickle cell anaemia • F8 gene, factor VIII and haemophilia • HTT gene, huntingtin and Huntington’s disease

SouravNovember 1, 2024

Answer

The relationship between genes, proteins, and phenotypes is fundamental to understanding how genetic information is expressed in living organisms. Genes are segments of DNA that encode instructions for synthesizing proteins, which perform various functions in the body and ultimately influence an organism’s phenotype—its observable traits. Let’s explore this relationship through specific examples of genes and associated conditions:

1. TYR Gene, Tyrosinase, and Albinism

• Gene: The TYR gene (tyrosinase) is located on chromosome 11 and encodes the enzyme tyrosinase.
• Protein: Tyrosinase is crucial for the production of melanin, the pigment responsible for coloration in the skin, hair, and eyes. It catalyzes the first two steps of melanin biosynthesis, converting the amino acid tyrosine to dopa and then to dopaquinone.
• Phenotype: Albinism is a condition characterized by a lack of melanin production. Mutations in the TYR gene can lead to reduced or absent tyrosinase activity, resulting in hypopigmentation. Individuals with albinism typically have very light skin, hair, and eyes, and they are at a higher risk for sun damage and vision problems due to the lack of pigment in the eyes.

2. HBB Gene, Hemoglobin, and Sickle Cell Anemia

• Gene: The HBB gene encodes the beta-globin subunit of hemoglobin, the protein responsible for transporting oxygen in the blood. It is located on chromosome 11.
• Protein: Hemoglobin is a tetramer made up of two alpha and two beta globin chains. It binds oxygen in the lungs and releases it in tissues.
• Phenotype: Sickle cell anemia is caused by a mutation in the HBB gene, specifically a single nucleotide change (adenine to thymine) that leads to the substitution of valine for glutamic acid in the beta-globin chain. This change causes hemoglobin to polymerize under low oxygen conditions, leading to the distortion of red blood cells into a sickle shape. These abnormally shaped cells can block blood flow, cause pain, and lead to various complications, including anemia and increased susceptibility to infections.

3. F8 Gene, Factor VIII, and Hemophilia A

• Gene: The F8 gene is located on the X chromosome and encodes factor VIII, a protein essential for blood coagulation.
• Protein: Factor VIII functions as a cofactor for factor IXa in the coagulation cascade, facilitating the conversion of factor X to Xa, which is crucial for forming a blood clot.
• Phenotype: Hemophilia A is an X-linked recessive disorder caused by mutations in the F8 gene that result in deficient or dysfunctional factor VIII. Individuals with hemophilia A have a reduced ability to form blood clots, leading to prolonged bleeding episodes, easy bruising, and joint problems. Since the gene is on the X chromosome, males (who have only one X chromosome) are more severely affected than females.

4. HTT Gene, Huntingtin, and Huntington’s Disease

• Gene: The HTT gene is located on chromosome 4 and encodes the protein huntingtin.
• Protein: Huntingtin is involved in various cellular processes, including neuronal development and transport. The precise function of huntingtin is not fully understood, but it is known to interact with numerous proteins in the cell.
• Phenotype: Huntington’s disease is caused by an expansion of CAG repeats in the HTT gene, leading to the production of an abnormal version of the huntingtin protein. This mutant protein aggregates in neurons, causing cell death. The disease is characterized by motor dysfunction, cognitive decline, and psychiatric symptoms, typically manifesting in mid-adulthood. The phenotypic effects of Huntington’s disease are progressive, leading to severe disability and ultimately death.