16.2.6 Genes, Proteins & Phenotype

• A gene can affect a phenotype of an organism
  • A gene codes for a single protein
  • The protein affects the phenotype through a particular mechanism

• The phenotype of an individual can also be affected by the environment

Genes code for mRNA which gets translated into a polypeptide (protein) that affects the phenotype of the organism

TYR gene & albinism

• Humans with albinism lack the pigment melanin in their skin, hair and eyes
• This causes them to have very pale skin, very pale hair and pale blue or pink irises in the eyes
• There is a metabolic pathway for producing melanin:

1. The amino acid tyrosine is converted to DOPA by the enzyme tyrosinase
2. DOPA is converted to dopaquinone again by the enzyme tyrosinase
3. Dopaquinone is converted to melanin

tyrosine → DOPA → dopaquinone → melanin

• A gene called TYR located on chromosome 11 codes for the enzyme tyrosinase
• There is a recessive allele for the gene TYR that causes a lack of enzyme tyrosinase or the presence of inactive tyrosinase
• Without the tyrosinase enzyme tyrosine can not be converted into melanin

HBB gene & sickle cell anaemia

• Sickle cell anaemia is a condition that causes individuals to have frequent infections, episodes of pain and anaemia
• Humans with sickle cell anaemia have abnormal haemoglobin in their red blood cells
• β-globin is a polypeptide found in haemoglobin that is coded for by the gene HBB which is found on chromosome 11
• There is an abnormal allele for the gene HBB which produces a slightly different amino acid sequence to the normal allele
  • The change of a single base in the DNA of the abnormal allele results in an amino acid substitution
    • The DNA base sequence GAG is replaced by GTG
      • This means that CTC is replaced by CAC on the complementary DNA template strand, meaning that GAG is replaced by GUG in the resulting mRNA
  • This change in amino acid sequence results in an abnormal β-globin polypeptide
    • The amino acid Glu is replaced with Val
• The abnormal β-globin in haemoglobin affects the structure and shape of the red blood cells
  • They are pulled into a half moon shape
  • They are unable to transport oxygen around the body
  • They stick to each other and clump together blocking capillaries
• A homozygous individual that has two abnormal alleles for the HBB gene produces only sickle cell haemoglobin
  • They have sickle cell anaemia and suffer from the associated symptoms
• A heterozygous individual that has one normal allele and one abnormal allele for the HBB gene will produce some normal haemoglobin and some sickle cell haemoglobin
  • They are a carrier of the allele
  • They may have no symptoms

Normal red blood cells and Sickle cell blood cells - The sickle cells cause a blockage in the capillary and restrict blood flow

F8 gene & haemophilia

• Factor VIII is a coagulating agent that plays an essential role in blood clotting
• The gene F8 codes for the Factor VIII protein
• There are abnormal alleles of the F8 gene that result in:
  • Production of abnormal forms of factor VIII
  • Less production of normal factor VIII
  • No production of factor VIII

• A lack of normal factor VIII prevents normal blood clotting and causes the condition haemophilia
• The F8 gene is located on the X chromosome
  • This means F8 is a sex-linked gene
  • Haemophilia is a sex-linked condition
  • If males have an abnormal allele they will have the condition as they have only one copy of the gene
  • Females can be heterozygous for the F8 gene and not suffer from the condition but act as a carrier

HTT gene & Huntington's disease

• Huntington’s disease is a genetic condition that develops as a person ages
• Usually a person with the disease will not show symptoms until they are 30 years old +
• An individual with the condition experiences neurological degeneration; they lose their ability to walk, talk and think
• The disease is ultimately fatal
• It has been found that individuals with Huntington's disease have abnormal alleles of the HTT gene
  • The HTT gene codes for the protein huntingtin which is involved in neuronal development
  • People that have a large number (>40) of repeated CAG triplets present in the nucleotide sequence of their HTT gene suffer from the disease

• The abnormal allele is dominant over the normal allele
  • If an individual has one abnormal allele present they will suffer from the disease

Gene, protein & phenotype summary table