Albinism, sickle cell anaemia, haemophilia and Huntington's disease look nothing alike, but each follows the same chain: a change in the base sequence of one gene changes a protein, and the faulty protein changes the phenotype. The height of a pea plant follows the same logic through a gibberellin enzyme.
A gene's base sequence determines the amino acid sequence of a polypeptide, which determines how it folds and so its function; the protein's activity then produces the phenotype. The TYR gene codes for tyrosinase, which converts tyrosine to melanin; a recessive allele gives a non-functional enzyme and albinism. The HBB gene codes for β-globin; a single base substitution replaces glutamic acid with valine, giving HbS, which forms fibres at low oxygen and causes sickle cell anaemia. The F8 gene on the X chromosome codes for clotting factor VIII; a recessive allele causes haemophilia. The HTT gene codes for huntingtin; a dominant allele with too many CAG repeats causes Huntington's disease. In peas, the dominant allele Le codes for a functional enzyme that makes active gibberellin (GA1), which causes stem elongation; lele plants make a non-functional enzyme and are dwarf.
Fig. 1: four human genes, the proteins they code for and the phenotype of the mutant allele
Section 01
Four genes, four proteins.
Choose TYR, HBB, F8 and HTT in turn. For each, compare the normal allele with the mutant allele: watch the coloured base sequence, the shape of the protein and the phenotype shown underneath.
Gene
Protein and its job
What the mutant allele does
Phenotype
TYR (autosomal, recessive mutant)
tyrosinase: an enzyme in melanocytes that converts the amino acid tyrosine into the pigment melanin
codes for a non-functional tyrosinase, so no melanin is made
albinism: very pale skin and hair, pale eyes and poor vision, in homozygous recessive people
HBB (autosomal, codominant alleles HbA, HbS)
β-globin, two of which are in each haemoglobin molecule
one base substitution (CTC to CAC in the template strand, so GAG becomes GUG in the mRNA) puts valine in place of glutamic acid at position 6
sickle cell anaemia in HbSHbS; sickle cell trait in heterozygotes
F8 (on the X chromosome, recessive mutant)
factor VIII: a protein in the cascade of reactions that forms a fibrin blood clot
codes for little or no working factor VIII
haemophilia: blood clots very slowly; far more common in males
HTT (autosomal, dominant mutant)
huntingtin: a protein needed in nerve cells; its gene has a repeated CAG triplet (normally fewer than about 27 repeats)
has many extra CAG repeats (more than about 36), so the protein has a long chain of glutamine, misfolds and forms clumps
Huntington's disease: neurones in the brain die, causing loss of movement control and mental decline, usually from middle age
Why valine matters: glutamic acid is charged and hydrophilic; valine is non-polar and hydrophobic. At low oxygen concentration the HbS molecules stick together into long fibres, distorting red blood cells into sickle shapes that carry less oxygen and block capillaries.
Dominant or recessive: a recessive mutant usually makes a protein that does not work, and one normal allele makes enough working protein. The HTT mutant is dominant because the faulty protein itself is harmful, even with a normal copy present.
Examiner trap
Link every step: gene → base sequence → amino acid sequence (primary structure) → folding and shape → protein function → phenotype. Marks are lost when an answer jumps straight from "mutation" to "disease".
Stage 1 · Learn
Check what the sim just showed you
Four quick checks. Each correct answer earns XP and records this skill on your profile.
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In the simulator, what does the TYR mutant allele lead to?
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For HBB, which change in the protein does the simulator describe?
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Why is haemophilia far more common in males, as the simulator notes for F8?
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What is different about the HTT mutant allele in the simulator?
Section 02
Gibberellin and the Le gene.
Plant height is also controlled by an enzyme. In peas, a single gene decides whether a plant makes enough gibberellin to grow tall.
Gibberellins are plant growth regulators. Active gibberellin, GA1, causes stem elongation by stimulating cell division and cell elongation in the internodes.
The Le gene codes for an enzyme in the gibberellin synthesis pathway that converts the inactive precursor GA20 into active GA1.
Dominant allele Le: codes for a functional enzyme. LeLe and Lele plants make plenty of GA1 and have long internodes: tall. One copy is enough.
Recessive allele le: a single base substitution changes one amino acid (alanine to threonine) near the active site, giving a non-functional enzyme. lele plants make very little GA1 and have short internodes: dwarf.
Evidence: spraying a lele dwarf plant with GA1 makes it grow tall, showing the dwarfism is caused by lack of gibberellin, not by an inability to respond to it.
Stage 2 · Exam
Exam-style questions
Unlocks once the four checks above are done. Worth more XP, written to A Level Paper 4 standard.
Finish the four checks above to unlock the exam questions
Exam style+20 XP
Why does a person heterozygous for a recessive TYR allele have normal pigmentation?
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Why is Huntington's disease inherited as a dominant condition?
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A dwarf pea plant (lele) is sprayed with GA1 and grows tall. What does this show?
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In sickle cell anaemia, how does replacing glutamic acid with valine change the haemoglobin?
Skill unlocked
Genes, proteins and phenotype, mastered.
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