What you'll learn
- How genes, alleles, genotypes and phenotypes link together.
- How to use genetic diagrams to predict monohybrid inheritance.
- How to calculate probabilities for inherited conditions such as cystic fibrosis.
- What genetic screening can and cannot tell you.
1. The genetic starting point
In humans, most body cells are diploid, meaning they contain two sets of chromosomes: one set inherited from the mother and one from the father. A chromosome is a long DNA molecule wrapped around proteins.
DNA, or deoxyribonucleic acid, contains coded instructions for making proteins or functional RNA molecules. These instructions are organised into genes.
Gene, locus and allele
- A gene is a length of DNA that codes for a polypeptide or a functional RNA.
- A locus is the fixed position of a gene on a chromosome.
- An allele is a different version of the same gene.
Most genes are found in pairs in body cells because chromosomes occur as homologous pairs. Homologous chromosomes have the same genes at the same loci, but they may carry different alleles.
2. From genotype to phenotype
Your genotype is the combination of alleles you have for a gene. Your phenotype is the observable characteristic produced, such as having or not having a genetic condition. Phenotype is often affected by genotype, but environment can also matter.
For a simple monohybrid inheritance question, you usually track two alleles of one gene. For example, you might use:
- C for a normal dominant allele
- c for a recessive allele linked to a condition
Key genotype words
- Homozygous means having two identical alleles, such as CC or cc.
- Heterozygous means having two different alleles, such as Cc.
- A dominant allele is expressed in the phenotype when only one copy is present.
- A recessive allele is only expressed in the phenotype when two copies are present.
A carrier is heterozygous for a recessive allele. For example, a person with genotype Cc may be unaffected but can pass the recessive allele c to their children.
Dominant does not mean common
A dominant allele is not necessarily the most frequent allele in a population. “Dominant” only describes how the allele behaves in a heterozygous genotype.
3. Why gametes carry one allele
A gamete is a sex cell, such as a sperm cell or egg cell. Gametes are haploid, meaning they contain one set of chromosomes rather than two.
Gametes are produced by meiosis, a type of cell division that separates homologous chromosomes. This means each gamete receives only one allele from each pair.
Segregation of alleles
During meiosis, the two alleles for a gene separate into different gametes. Fertilisation then randomly combines one allele from each parent.
This is why a heterozygous parent, such as Cc, can make two types of gamete: some carrying C and some carrying c.
4. Monohybrid inheritance
Monohybrid inheritance is the inheritance of a characteristic controlled by one gene. In A-Level questions, you are often asked to predict offspring genotypes and phenotypes using a Punnett square, which is a grid showing possible allele combinations after fertilisation.
The diagram below shows a typical monohybrid cross for an autosomal recessive condition. Autosomal means the gene is on a non-sex chromosome.
Using a Punnett square
A Punnett square is not just a box-filling exercise. It is a probability model. Each box represents one possible combination of gametes.
Calculating offspring probabilities
Two parents are both carriers for a recessive condition. Use C for the normal dominant allele and c for the recessive disease allele.
- The parents must both be heterozygous, so the cross is Cc with Cc.
- Each parent can produce two gamete types, C and c, because their alleles separate during meiosis.
- Combining the gametes gives four possible offspring genotypes: CC, Cc, Cc and cc.
- Only cc is affected, so the probability of an affected child is 14\frac{1}{4}41, which is 25%.
- The carrier genotypes are Cc and Cc, so the probability of an unaffected carrier child is 24\frac{2}{4}42, which is 50%.
For two heterozygous parents with complete dominance, the typical genotype ratio is:
CC : Cc : cc = 1 : 2 : 1
The typical phenotype ratio is:
unaffected : affected = 3 : 1
Keep the allele letters consistent
Use the same letter for both alleles, with upper case for the dominant allele and lower case for the recessive allele. For example, use C and c, not C and d.
5. Probability across more than one child
Each fertilisation event is independent. This means the genotype of one child does not change the probability for the next child.
Calculating a two-child probability
For two carrier parents, the probability of an affected child is 14\frac{1}{4}41 and the probability of an unaffected child is 34\frac{3}{4}43. What is the probability that exactly one of two children is affected?
- There are two possible orders: affected then unaffected, or unaffected then affected.
- The probability of affected then unaffected is 14×34=316\frac{1}{4} \times \frac{3}{4} = \frac{3}{16}41×43=163.
- The probability of unaffected then affected is also 34×14=316\frac{3}{4} \times \frac{1}{4} = \frac{3}{16}43×41=163.
- Add the two possible orders: 316+316=616\frac{3}{16} + \frac{3}{16} = \frac{6}{16}163+163=166.
- Therefore the probability is 38\frac{3}{8}83, which is 37.5%.
Resetting the probability
If a carrier couple already has one affected child, the chance that their next child is affected is still 25%. Previous children do not “use up” any outcomes.
6. Interpreting family patterns
A pedigree diagram shows inheritance through a family. Even without drawing one, you can often infer likely genotypes from the pattern.
For an autosomal recessive condition:
- affected individuals are usually homozygous recessive
- unaffected parents can have an affected child if both are carriers
- the condition can appear to “skip” generations
- males and females are usually affected in similar numbers
Inferring carriers from an affected child
Two unaffected parents have a child with an autosomal recessive condition. What can you infer?
- The affected child must be homozygous recessive, such as cc.
- The child must have inherited one c allele from each parent.
- Since both parents are unaffected, each must also have a dominant C allele.
- Therefore both parents must be carriers with genotype Cc.
- For any future child, the chance of being affected is again 14\frac{1}{4}41.
For an autosomal dominant condition, an affected person usually has at least one affected parent, because only one copy of the dominant allele is needed for the phenotype.
7. Genetic screening
Genetic screening means testing individuals or groups to identify the presence of particular alleles, mutations or genetic conditions. A mutation is a change in the DNA base sequence.
Genetic screening
Genetic screening uses biological samples to estimate whether a person has a particular genotype, carries a particular allele, or has an increased risk of developing or passing on a condition.
A screening workflow has the same overall logic whether the sample comes from an adult, newborn baby, embryo or foetus.
Screening often involves extracting DNA, copying a target region using PCR, which stands for polymerase chain reaction, and detecting a known allele using a DNA probe, sequencing or gel electrophoresis.
8. Types of genetic screening
Genetic screening can be used at different stages of life.
Carrier screening
This tests whether an unaffected person carries a recessive allele. It can help couples estimate the chance of having a child with an inherited condition, such as cystic fibrosis.
Prenatal testing
This tests cells from a developing foetus. Samples may be obtained using chorionic villus sampling, which takes placental tissue, or amniocentesis, which samples amniotic fluid. These can provide genetic information, but invasive procedures carry some risk.
Preimplantation genetic testing
This is used with IVF, or in vitro fertilisation. Embryos are tested before implantation, and an embryo without the tested condition may be selected.
Newborn screening
This identifies conditions soon after birth, especially where early treatment can reduce harm.
A screen is not a decision
Genetic screening provides information. Genetic counselling helps people understand risk, uncertainty and options before making personal decisions.
9. Interpreting screening results
A positive result may show that an allele has been detected. A negative result may reduce the estimated risk, but it does not always make the risk zero. This is because tests may only detect known mutations, and no screening test is perfect.
Using a carrier-screening result
A woman is known to be a carrier for a recessive condition. Her partner tests negative, but the counsellor estimates his remaining chance of being a carrier as 1 in 100. What is the chance of an affected child?
- An affected child must inherit the recessive allele from both parents.
- The mother is definitely a carrier, but the father only has a 1100\frac{1}{100}1001 chance of being a carrier.
- If both parents are carriers, the chance of an affected child is 14\frac{1}{4}41.
- Multiply the probabilities: P(affected)=1100×14=1400P(\text{affected}) = \frac{1}{100} \times \frac{1}{4} = \frac{1}{400}P(affected)=1001×41=4001.
- So the chance of an affected child is 1 in 400, which is 0.25%.
Screening has limitations
A false positive suggests a condition or allele is present when it is not. A false negative misses a condition or allele that is present. Always treat screening results as part of a wider clinical and counselling process.
10. Benefits and ethical issues
Genetic screening can be very useful because it may allow:
- early treatment or monitoring
- informed reproductive choices
- identification of carriers in a family
- preparation and support for parents
However, it also raises ethical and social issues, including:
- psychological stress from risk information
- confidentiality, because results may affect biological relatives
- informed consent, especially for children or embryos
- possible discrimination or stigma
- difficult decisions after prenatal or preimplantation testing
In the exam
- State the alleles clearly before drawing a genetic diagram, including which allele is dominant or recessive.
- Show parent genotypes, gametes, offspring genotypes and phenotypes; do not skip straight to a ratio.
- For screening questions, separate the biological result from the ethical decision, and mention counselling where appropriate.
Check yourself
- Why can two unaffected parents have a child with an autosomal recessive condition?
- In a Cc with Cc cross, what are the genotype and phenotype ratios?
- Why does a negative genetic screening result not always mean zero risk?
