What is a genetic disorder?
A gene is a short piece of DNA. It is an instruction to make one protein. A mutation is a change in that instruction. Many mutations do nothing. Some change the protein so it does not work. Then a genetic disorder can appear.
There are three main groups:
- Single-gene disorders: one gene is faulty (cystic fibrosis, sickle cell anaemia, thalassaemia, Huntington disease, haemophilia).
- Chromosome disorders: whole chromosomes are extra, missing or broken (Down syndrome, Turner syndrome, Klinefelter syndrome).
- Multifactorial disorders: many genes plus lifestyle and environment (type 2 diabetes, some heart disease, some cancers).
Genetic disorders are not caught like a cold. They are passed down in families, or they start new in one egg or sperm cell.
Recessive and dominant single-gene disorders
You get one copy of each gene from each parent. We write the normal allele with a capital letter and the faulty one with a small letter.
Autosomal recessive
You need two faulty copies (aa) to be ill. A person with Aa is a carrier: healthy, but can pass the faulty copy on. Two carriers: AA : Aa : aa = 1 : 2 : 1, so a 25% chance of an affected child. Examples: cystic fibrosis (thick mucus in lungs), sickle cell anaemia (red blood cells bend into a sickle shape), thalassaemia (too little haemoglobin), phenylketonuria.
Autosomal dominant
One faulty copy (D) is enough. An affected parent (Dd) and a healthy parent (dd) have a 50% chance with each child. Example: Huntington disease (nerve cells slowly damaged, signs usually start in adult life), achondroplasia (a form of short stature).
“Autosomal” means the gene is on chromosomes 1 to 22, not on X or Y, so boys and girls are affected equally.
Sex-linked (X-linked) disorders
Girls are XX and boys are XY. The Y chromosome carries very few genes. If a faulty recessive allele (Xʰ) is on the X, a boy has no second X to cover it. So X-linked recessive disorders are much more common in boys.
Carrier mother (XᴴXʰ) × healthy father (XᴴY): daughters XᴴXᴴ or XᴴXʰ (half are carriers, none ill), sons XᴴY or XʰY (half affected).
Examples: haemophilia (blood does not clot well; famous in Queen Victoria's royal descendants), red–green colour blindness, Duchenne muscular dystrophy. A father never passes an X-linked allele to his son, because he gives his son the Y.
Chromosome disorders
Sometimes chromosome pairs do not separate properly when eggs or sperm are made. This is called non-disjunction. A gamete then has one chromosome too many or too few.
- Down syndrome (trisomy 21): three copies of chromosome 21, 47 in total. Learning difficulty, a flat face and heart problems are common. The chance rises with the mother's age.
- Turner syndrome (45, X): a girl with one X. Short height, ovaries do not develop.
- Klinefelter syndrome (47, XXY): a boy with an extra X. Often tall, low fertility.
A karyotype is a picture of all chromosomes, sorted in pairs by size. Doctors count them to find these disorders.
Testing, counselling and treatment
Pedigree charts are family trees that show who had a trait. They help to guess if a disorder is dominant, recessive or X-linked.
Genetic testing looks at DNA or chromosomes: carrier tests for adults, prenatal tests (from the mother's blood, amniotic fluid or placenta cells) and newborn screening (a heel-prick blood test for phenylketonuria and others).
Genetic counselling: a trained expert explains the chances and the choices, without forcing a decision.
Treatment: special diets (phenylketonuria), clotting-factor injections (haemophilia), blood transfusions and bone-marrow transplants (thalassaemia). Gene therapy puts a working copy of the gene into the patient's cells using a harmless virus or gene editing (CRISPR). It is new, costly and raises ethical questions, such as who should get it and whether to change genes in embryos.
Try it: draw your own Punnett square
Take a sheet of paper. Draw a 2 × 2 grid. Write the mother's two alleles along the top and the father's two down the side. Fill each box with one letter from the top and one from the side. Count how many boxes are aa. Now check your answer with the free-play step of the 3D. Try XᴴXʰ × XʰY: can a daughter be affected?
Key formulas and definitions
- Carrier × carrier (Aa × Aa) → 1 AA : 2 Aa : 1 aa → 25% affected, 50% carriers
- Affected dominant × healthy (Dd × dd) → 50% affected
- Carrier mother × healthy father (XᴴXʰ × XᴴY) → 50% of sons affected, 50% of daughters carriers
- Down syndrome = trisomy 21 → 47 chromosomes
Worked examples
1. Two parents are both carriers of cystic fibrosis (Ff). What is the chance that their child has cystic fibrosis?
Punnett square: FF, Ff, Ff, ff. Only ff is affected: 1 of 4 boxes = 25%. Two of 4 (50%) are carriers like the parents.
2. A man with Huntington disease (Hh) has children with a woman who is hh. What fraction of children may get the disease?
Father gives H or h; mother always gives h. Children: Hh, Hh, hh, hh. Hh is affected because the allele is dominant: 2/4 = 50%.
3. A woman who carries haemophilia (XᴴXʰ) marries a man with haemophilia (XʰY). Can a daughter have haemophilia?
Daughters get Xʰ from the father and Xᴴ or Xʰ from the mother: XᴴXʰ (carrier) or XʰXʰ (affected). So yes, 50% of daughters could be affected. Sons get Y from father: XᴴY or XʰY, 50% affected.
4. A karyotype shows 47 chromosomes with three copies of chromosome 21. Name the disorder and the error that causes it.
Down syndrome (trisomy 21). It is caused by non-disjunction: chromosome 21 did not separate during meiosis, so one gamete had two copies instead of one.
Common mistakes
- Thinking carriers are ill. A carrier (Aa) is healthy; only aa shows a recessive disorder.
- Saying a 25% chance means exactly one in every four children will be affected. Each child has its own 1 in 4 chance; a family can have zero or several affected children.
- Believing a father can pass an X-linked disorder to his son. A father gives his son the Y chromosome, never his X.
- Mixing up gene disorders and chromosome disorders. Down syndrome is not a faulty gene; it is a whole extra chromosome.