Genetic disorders: sickle-cell anaemia, haemophilia, Down syndrome

What you'll learn

This revision guide covers three major genetic disorders tested in the CXC CSEC Human and Social Biology examination: sickle-cell anaemia, haemophilia, and Down syndrome. You will understand the causes, inheritance patterns, symptoms, and effects of each condition, with emphasis on Caribbean populations where sickle-cell anaemia has particular relevance.

Key terms and definitions

Genetic disorder — a condition caused by abnormalities in an individual's DNA that can be inherited or arise from chromosomal mutations

Allele — an alternative form of a gene; individuals inherit two alleles for each gene, one from each parent

Homozygous — having two identical alleles for a particular gene (e.g., HbS HbS or HbA HbA)

Heterozygous — having two different alleles for a particular gene (e.g., HbA HbS)

Sex-linked inheritance — the inheritance pattern of genes located on sex chromosomes, particularly the X chromosome

Carrier — an individual who possesses one copy of a recessive allele for a genetic disorder but does not show symptoms

Mutation — a change in the DNA sequence that can lead to altered gene function or expression

Chromosome — a thread-like structure of DNA and protein that carries genetic information; humans normally have 46 chromosomes in 23 pairs

Core concepts

Sickle-cell anaemia

Cause and genetic basis

Sickle-cell anaemia results from a mutation in the gene coding for haemoglobin, the oxygen-carrying protein in red blood cells. The normal haemoglobin allele is designated HbA, while the sickle-cell allele is HbS.

The mutation causes a single amino acid substitution in the haemoglobin molecule:

• Glutamic acid is replaced by valine at position 6 of the beta-globin chain
• This produces abnormal haemoglobin (HbS) that distorts red blood cells into a sickle (crescent) shape when oxygen levels are low

Inheritance pattern

Sickle-cell anaemia follows an autosomal recessive inheritance pattern:

• HbA HbA (homozygous normal) — individual has normal haemoglobin and no sickle-cell trait
• HbA HbS (heterozygous) — individual is a carrier with sickle-cell trait; usually asymptomatic but may experience symptoms under extreme conditions (low oxygen, high altitude, dehydration)
• HbS HbS (homozygous recessive) — individual has sickle-cell anaemia with severe symptoms

When both parents are carriers (HbA HbS × HbA HbS):

• 25% chance of HbA HbA (normal)
• 50% chance of HbA HbS (carrier)
• 25% chance of HbS HbS (sickle-cell anaemia)

Symptoms and effects

Individuals with sickle-cell anaemia (HbS HbS) experience:

• Anaemia — sickled red blood cells are fragile and break down rapidly, reducing oxygen-carrying capacity
• Pain crises — sickled cells block small blood vessels, causing severe pain in bones, joints, abdomen, and chest
• Fatigue and weakness — due to reduced oxygen delivery to tissues
• Frequent infections — damage to the spleen reduces immune function
• Delayed growth and development — chronic oxygen shortage affects physical development in children
• Organ damage — blocked blood vessels can damage the kidneys, liver, lungs, and brain
• Stroke — particularly in children, due to blocked blood vessels in the brain

Caribbean relevance

Sickle-cell anaemia is particularly prevalent in Caribbean populations due to ancestry from West Africa, where the sickle-cell allele provides protection against malaria. Countries like Jamaica, Trinidad and Tobago, and Barbados have established screening programmes for newborns. Approximately 1 in 150 babies born in Jamaica has sickle-cell disease, while 1 in 10 carries the trait.

Haemophilia

Cause and genetic basis

Haemophilia is a bleeding disorder caused by the absence or deficiency of blood clotting factors. The most common form, Haemophilia A, results from a deficiency of clotting Factor VIII, while Haemophilia B involves Factor IX deficiency.

The gene for Factor VIII is located on the X chromosome, making haemophilia a sex-linked recessive disorder.

Inheritance pattern

Because haemophilia is X-linked:

Males (XY):

• XH Y — normal male
• Xh Y — male with haemophilia (cannot be a carrier)

Females (XX):

• XH XH — normal female
• XH Xh — carrier female (usually asymptomatic)
• Xh Xh — female with haemophilia (extremely rare)

When a carrier female (XH Xh) has children with a normal male (XH Y):

• 25% chance of normal male (XH Y)
• 25% chance of haemophiliac male (Xh Y)
• 25% chance of normal female (XH XH)
• 25% chance of carrier female (XH Xh)

Males are much more likely to have haemophilia because they only need one copy of the recessive allele (Xh), while females would need two copies.

Symptoms and effects

Individuals with haemophilia experience:

• Prolonged bleeding — cuts and injuries bleed for extended periods
• Spontaneous bleeding — bleeding into joints (haemarthrosis), muscles, and soft tissues without obvious injury
• Joint damage and arthritis — repeated bleeding into joints causes permanent damage
• Internal bleeding — potentially life-threatening bleeding in the brain, abdomen, or other organs
• Easy bruising — minor bumps cause extensive bruising
• Blood in urine or stool — from internal bleeding

Treatment involves replacement of the missing clotting factor through regular infusions. Individuals must avoid activities with high injury risk and take precautions during dental work or surgery.

Down syndrome

Cause and genetic basis

Down syndrome (also called Trisomy 21) results from chromosomal abnormality rather than a single gene mutation. Individuals with Down syndrome have an extra copy of chromosome 21, giving them 47 chromosomes instead of the normal 46.

Three types of chromosomal abnormalities can cause Down syndrome:

Trisomy 21 (95% of cases) — three complete copies of chromosome 21 due to non-disjunction during meiosis (cell division that produces sex cells). The egg or sperm has an extra chromosome 21, which is then passed to the offspring.

Translocation (3-4% of cases) — part of chromosome 21 attaches to another chromosome, usually chromosome 14. The individual may have 46 chromosomes but still have extra chromosome 21 material.

Mosaicism (1-2% of cases) — only some body cells have three copies of chromosome 21, while others have the normal two copies.

Non-inheritance pattern

Unlike sickle-cell anaemia and haemophilia, Down syndrome typically occurs spontaneously and is not inherited in a predictable pattern.

Risk factors:

• Maternal age — the most significant risk factor; women over 35 have increased risk due to aging eggs being more prone to errors during meiosis
• At age 35, risk is approximately 1 in 350
• At age 40, risk increases to 1 in 100
• At age 45, risk is about 1 in 30

Translocation Down syndrome can be inherited if a parent carries a balanced translocation (has the rearranged chromosomes but no extra genetic material and no symptoms).

Characteristics and effects

Individuals with Down syndrome typically have:

Physical features:

• Distinctive facial appearance — flattened facial profile, small ears, upward slanting eyes
• Single crease across the palm (palmar crease)
• Short stature and short neck
• Poor muscle tone (hypotonia)
• Small hands and feet with short fingers

Medical conditions:

• Intellectual disability — ranging from mild to moderate learning difficulties
• Heart defects — approximately 50% have congenital heart problems
• Hearing and vision problems — increased risk of cataracts, hearing loss
• Increased susceptibility to infections — due to immune system abnormalities
• Thyroid problems — hypothyroidism is common
• Increased risk of leukaemia — particularly in childhood
• Early-onset Alzheimer's disease — increased risk in adulthood

With early intervention, medical care, and educational support, many individuals with Down syndrome lead productive, fulfilling lives. Life expectancy has increased significantly, now averaging 60 years in developed countries.

Comparing the three disorders

Worked examples

Example 1: Sickle-cell inheritance (6 marks)

Question: A man and woman are both carriers of the sickle-cell trait (HbA HbS). (a) Construct a genetic diagram to show the possible genotypes of their children. (4 marks) (b) State the probability that their child will have sickle-cell anaemia. (1 mark) (c) Explain why carriers of sickle-cell trait may have an advantage in malaria-endemic regions. (1 mark)

Model answer:

(a)

Parents:      HbA HbS    ×    HbA HbS
Gametes:      HbA, HbS        HbA, HbS

Offspring:
              HbA          HbS
    HbA    | HbA HbA  | HbA HbS |
    HbS    | HbA HbS  | HbS HbS |

Genotypes: 1 HbA HbA : 2 HbA HbS : 1 HbS HbS (Award 1 mark for parents' genotypes, 1 mark for gametes, 1 mark for offspring genotypes, 1 mark for ratio)

(b) 1 in 4 or 25% or 1/4 (1 mark)

(c) Carriers (HbA HbS) are more resistant to malaria than normal individuals (HbA HbA) because the malaria parasite cannot reproduce effectively in cells containing some sickle haemoglobin. This provides a selective advantage in regions where malaria is common. (1 mark for explanation of resistance/advantage)

Example 2: Haemophilia inheritance (5 marks)

Question: A carrier female for haemophilia (XH Xh) marries a normal male (XH Y). (a) Using a genetic diagram, show the possible genotypes of their children. (3 marks) (b) Explain why males are more likely to have haemophilia than females. (2 marks)

Model answer:

(a)

Parents:      XH Xh    ×    XH Y
Gametes:      XH, Xh         XH, Y

Offspring:
              XH           Y
    XH    | XH XH    | XH Y  |
    Xh    | XH Xh    | Xh Y  |

Genotypes: 1 normal female (XH XH) : 1 carrier female (XH Xh) : 1 normal male (XH Y) : 1 haemophiliac male (Xh Y) (Award 1 mark for parents and gametes, 1 mark for correct offspring, 1 mark for identification of phenotypes)

(b) Males have only one X chromosome, so if they inherit the haemophilia allele (Xh), they will have the disease (1 mark). Females have two X chromosomes, so they need two copies of the haemophilia allele to have the disease, which is very rare; one normal allele (XH) is usually sufficient to produce adequate clotting factor (1 mark).

Example 3: Down syndrome (4 marks)

Question: (a) State the chromosomal abnormality that causes Down syndrome. (1 mark) (b) Explain why maternal age is a risk factor for Down syndrome. (2 marks) (c) State ONE physical characteristic of Down syndrome. (1 mark)

Model answer:

(a) Three copies of chromosome 21 (trisomy 21) / an extra chromosome 21 / 47 chromosomes instead of 46 (1 mark)

(b) As women age, their eggs age as well (1 mark). Older eggs are more likely to make errors during meiosis/cell division, particularly during the separation of chromosomes (non-disjunction), leading to an extra chromosome 21 in the egg (1 mark).

(c) Any ONE of: flattened facial profile / upward slanting eyes / small ears / single palmar crease / short stature / short neck / poor muscle tone / small hands and feet (1 mark)

Common mistakes and how to avoid them

• Confusing carriers with affected individuals: Remember that carriers (HbA HbS or XH Xh) have one normal and one disease allele and usually do not show symptoms. Only homozygous recessive individuals (HbS HbS) or males with X-linked conditions (Xh Y) are affected. Always clearly distinguish between carrier and affected phenotypes in genetic diagrams.

• Incorrect genetic diagram notation: Use consistent, correct notation: HbA and HbS for sickle-cell alleles; XH and Xh for haemophilia. Show both alleles for each individual (e.g., HbA HbS, not just HbA or S). For sex-linked traits, always attach the allele to the X chromosome (XH or Xh), not written separately.

• Forgetting that haemophilia is sex-linked: When constructing genetic diagrams for haemophilia, you must use X and Y chromosomes with the alleles attached to X. Do not treat it like an autosomal trait. Remember males cannot be carriers—they either have haemophilia or they don't.

• Stating Down syndrome is inherited like other genetic disorders: Down syndrome (trisomy 21) usually occurs spontaneously due to non-disjunction during meiosis and is not inherited in a predictable Mendelian pattern. Do not construct Punnett squares for Down syndrome as you would for sickle-cell anaemia or haemophilia.

• Mixing up symptoms between disorders: Keep symptoms specific to each condition. Sickle-cell causes pain crises and anaemia; haemophilia causes prolonged bleeding and joint problems; Down syndrome causes intellectual disability and distinctive physical features. Do not attribute bleeding problems to sickle-cell or anaemia to haemophilia.

• Incomplete genetic diagrams: Always include: (1) parents' genotypes, (2) gametes produced, (3) offspring genotypes in a Punnett square, and (4) the ratio or probability requested. Missing any component loses marks.

Exam technique for "Genetic disorders: sickle-cell anaemia, haemophilia, Down syndrome"

• Master genetic diagram construction: The CXC CSEC exam frequently asks for genetic diagrams (Punnett squares). Practice drawing neat, clearly labelled diagrams showing parents' genotypes, possible gametes, and offspring combinations. Always state the phenotype ratio or probability when asked. Genetic diagram questions typically carry 3-5 marks, so each step matters.

• Understand command words: "State" requires a brief answer (1 mark); "Explain" requires reasoning or mechanism (2-3 marks); "Describe" requires characteristics or process details (2-3 marks); "Compare" requires similarities and differences. Allocate your answer length and detail to match the marks available.

• Link structure to function: When explaining how genetic disorders affect the body, connect the genetic cause to the physical symptom. For example: "The mutation produces abnormal haemoglobin (HbS) → red blood cells become sickle-shaped → sickled cells block blood vessels → causes pain crises." This chain of reasoning earns multiple marks.

• Use Caribbean context appropriately: If a question mentions Caribbean populations or gives a regional scenario, incorporate relevant knowledge. For sickle-cell questions, you might mention screening programmes in Jamaica or the historical link to malaria protection. This demonstrates understanding of real-world application.

Quick revision summary

Three major genetic disorders are testable at CSEC level: sickle-cell anaemia (autosomal recessive, abnormal haemoglobin causing sickled red blood cells), haemophilia (sex-linked recessive, deficiency of blood clotting factors affecting mainly males), and Down syndrome (trisomy 21, extra chromosome 21 causing intellectual disability and physical characteristics). Sickle-cell and haemophilia follow Mendelian inheritance with carriers possible; Down syndrome results from chromosomal non-disjunction, typically spontaneous, with maternal age as a key risk factor. Know the causes, inheritance patterns, symptoms, and how to construct accurate genetic diagrams for each disorder.