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16.13 Gene-Protein-Phenotype Relationship

Posted14/11/2024
Updated29/12/2024
ByBMF
Views19

Overview

  • Genotype vs. Phenotype:
    • Genotype: The genetic makeup of an organism; the specific alleles present.
    • Phenotype: The observable characteristics or traits resulting from the genotype and environmental interactions.
  • Gene Function:
    • Genes code for proteins, which carry out essential biological functions.
    • Proteins act as enzymes, structural components, signaling molecules, and more.
  • Impact of Mutations:
    • Mutations: Changes in the DNA sequence that can alter protein structure and function.
    • Consequences: Can lead to various phenotypic outcomes, ranging from benign to severe disorders.

Gene Symbols

  • Standard Notation:
    • Human Genes: Represented by three-letter abbreviations in italics (e.g., TYR for the tyrosinase gene).
    • Protein Products: Denoted by the same three-letter abbreviation in regular type (e.g., TYR for the tyrosinase enzyme).
  • Example:
    • HBB gene → HBB protein (Hemoglobin β chain)

Examples of Gene-Protein-Phenotype Relationships

  1. Albinism: The TYR Gene and Tyrosinase
    • Location: Chromosome 11
    • Gene Function: Encodes the tyrosinase enzyme, crucial for melanin synthesis.
    • Melanin Pathway:
      • Reaction Sequence: Tyrosine → DOPA → Dopaquinone → Melanin
    • Mutation Effect:
      • Type: Recessive allele mutation
      • Consequence: Absence or inactivity of tyrosinase enzyme
    • Phenotype:
      • Characteristics: Lack of melanin leads to pale skin, hair, and eyes; red-appearing pupils.
      • Additional Effects: Vision problems due to melanin’s role in eye development.
    • Inheritance Pattern:
      • Homozygous Recessive (tt): Displays albinism.
      • Heterozygous (Tt): Carrier without phenotype expression.
  2. Sickle Cell Anemia: The HBB Gene and Hemoglobin
    • Location: Chromosome 11
    • Gene Function: Codes for the β-globin chain of hemoglobin.
    • Normal Hemoglobin Function: Transports oxygen in red blood cells.
    • Mutation Effect:
      • Type: Single nucleotide substitution (A → T)
      • Amino Acid Change: Glutamic acid (Glu) → Valine (Val) at position 6
      • Result: Hemoglobin becomes insoluble under low oxygen conditions, causing red blood cells to deform into a sickle shape.
    • Phenotype:
      • Characteristics: Sickle-shaped cells block capillaries, reducing oxygen delivery.
      • Health Impacts: Chronic anemia, pain crises, increased risk of infections.
    • Inheritance Pattern:
      • Homozygous (HbS/HbS): Severe sickle cell disease.
      • Heterozygous (HbA/HbS): Carrier (sickle cell trait) with milder symptoms or asymptomatic.
  3. Hemophilia: The F8 Gene and Factor VIII
    • Location: X Chromosome (Sex-Linked)
    • Gene Function: Encodes coagulation factor VIII, vital for blood clotting.
    • Mutation Effect:
      • Type: Faulty or reduced production of factor VIII due to F8 gene mutation.
      • Consequence: Impaired blood clotting mechanism.
    • Phenotype:
      • Characteristics: Excessive bleeding from minor injuries, prolonged bleeding after surgery or dental work.
    • Inheritance Pattern:
      • Males (XY): Single faulty F8 allele results in hemophilia.
      • Females (XX): Heterozygous carriers typically do not show symptoms; homozygous females display hemophilia.
  4. Huntington’s Disease: The HTT Gene and Huntingtin
    • Location: Chromosome 4
    • Gene Function: Codes for the huntingtin protein, essential for neuron development and function.
    • Mutation Effect:
      • Type: Expanded CAG trinucleotide repeats (>40 repeats) in the HTT gene.
      • Consequence: Abnormal huntingtin protein leads to neuronal dysfunction and death.
    • Phenotype:
      • Characteristics: Progressive neurodegeneration, loss of motor control, cognitive decline, psychiatric symptoms.
      • Onset: Typically between ages 30-40.
      • Prognosis: Fatal within 15-20 years post-onset.
    • Inheritance Pattern:
      • Autosomal Dominant: Only one mutated allele is necessary to inherit the disease.
      • Transmission Risk: 50% chance of passing the mutated allele to offspring.
  5. Dwarfism in Peas: The Le Gene and Gibberellin
    • Function: Regulates the production of gibberellin (GA1), a plant hormone that promotes stem elongation.
    • Mutation Effect:
      • Type: Recessive allele (le) leads to a non-functional enzyme required for GA1 synthesis.
      • Consequence: Absence of gibberellin production.
    • Phenotype:
      • Characteristics: Short stature (dwarfism) in homozygous recessive plants (lele).
    • Phenotypic Rescue:
      • Method: External application of gibberellin can restore normal height in genetically dwarf plants.

Key Terms

  • Tyrosinase: An enzyme involved in the production of melanin; mutations in the TYR gene can cause albinism.
  • Hemoglobin (HBB): A protein in red blood cells responsible for oxygen transport; mutations in the HBB gene lead to sickle cell anemia.
  • Factor VIII (F8): A blood clotting protein; mutations in the F8 gene result in hemophilia.
  • Huntingtin (HTT): A protein essential for neuron function; mutations in the HTT gene cause Huntington’s disease.
  • Gibberellin (GA1): A plant hormone that promotes growth; its synthesis is regulated by the Le gene in peas.
  • Allele: Different versions of a gene that determine specific traits.
  • Homozygous: Having two identical alleles for a particular gene.
  • Heterozygous: Having two different alleles for a particular gene.
  • Autosomal Dominant: A pattern of inheritance where only one copy of a mutated gene is sufficient to cause a disorder.
  • Autosomal Recessive: A pattern of inheritance where two copies of a mutated gene are necessary to express the disorder.
  • Sex-Linked (X-Linked): Traits associated with genes located on the X chromosome, often affecting males more severely.
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