Cambridge A Level Biology 9700

Topic 16: Inheritance

Prepared for Kevin | May/June Series

The Big Picture

Inheritance is the study of how genetic information is passed from parents to offspring and
how that information determines the characteristics of an organism. This topic is heavily
calculation-based — Cambridge will give you genetic crosses and expect you to predict
ratios, identify genotypes, and explain deviations from expected ratios.
The key insight is this: genes are on chromosomes, chromosomes come in pairs, and during
meiosis those pairs are separated. This is what generates genetic variation and determines
the probability of offspring having particular phenotypes.

1. Essential Definitions — Learn Every One

Cambridge awards marks for precise use of these terms. Vague answers lose marks.

Term Definition
Gene A sequence of DNA base pairs that codes for a specific polypeptide (or
functional RNA). Located at a specific locus on a chromosome.
Locus The specific position of a gene on a chromosome. Alleles of the same
gene are found at the same locus on homologous chromosomes.
Allele One of two or more alternative forms of a gene, found at the same locus.
Different alleles may produce different phenotypes.
Dominant An allele that is expressed in the phenotype when present in one copy
(heterozygous) or two copies (homozygous). Denoted by a capital letter.
Recessive An allele that is only expressed in the phenotype when present in two
copies (homozygous). Masked by the dominant allele in heterozygotes.
Codominant Two alleles that are both fully expressed in the heterozygote — neither
masks the other. E.g. ABO blood group IA and IB alleles.
Genotype The alleles present in an organism for a particular gene (or set of genes).
E.g. Aa, AA, aa.
 Phenotype The observable characteristics of an organism — the physical expression
of the genotype, also influenced by the environment.
Homozygous Having two identical alleles for a gene. E.g. AA or aa.
Heterozygous Having two different alleles for a gene. E.g. Aa.
Linkage Genes located on the same chromosome are said to be linked. They tend
to be inherited together unless separated by crossing over.
F1 The first filial generation — offspring of the parental (P) generation cross.
F2 The second filial generation — offspring of two F1 individuals crossed
together.
Test cross A cross between an individual with an unknown genotype (dominant
phenotype) and a homozygous recessive individual. Used to determine if
the unknown genotype is homozygous dominant or heterozygous.

2. Meiosis and Genetic Variation

Meiosis is the reduction division that produces gametes. It produces cells that are HAPLOID
(n) from diploid (2n) parent cells. You covered the stages of meiosis in Topic 5 — here we
focus on HOW meiosis generates genetic variation.

Mechanism How it generates variation When it occurs

Crossing over Homologous chromosomes exchange Prophase I — chiasmata
segments during prophase I. This creates form between non-sister
new combinations of alleles (recombinant chromatids of homologous
chromosomes) that were not in either chromosomes
parent.
Independent Homologous pairs line up randomly at the Metaphase I — random
assortment (random equator during metaphase I. Either orientation of bivalents
orientation) chromosome of each pair can face either
pole. With 23 pairs in humans, this gives 2²³
possible chromosome combinations in
gametes.
Random fusion of Any male gamete can fuse with any female Fertilisation
gametes gamete at fertilisation, producing further
variation in offspring.

Haploid (n): A cell containing a single set of chromosomes — one chromosome from
each homologous pair. Human gametes are haploid: n = 23.

Diploid (2n): A cell containing two sets of chromosomes — homologous pairs. Most
 human body cells are diploid: 2n = 46.

Homologous chromosomes: A pair of chromosomes with the same genes at the same
loci. One is inherited from each parent. They are the same length, have the same
centromere position, and carry alleles of the same genes (which may be the same or
different alleles).

3. Monohybrid Inheritance
Monohybrid inheritance involves ONE gene with TWO alleles. The key ratios to know:
• Heterozygous × heterozygous (Aa × Aa) → 3 dominant : 1 recessive phenotype ratio
(F2 ratio)
• Heterozygous × homozygous recessive (Aa × aa) → 1 dominant : 1 recessive (test
cross ratio)

3.1 How to Set Out a Genetic Cross — Cambridge Format

Cambridge awards marks for the FORMAT of genetic crosses, not just the answer. Always
use this layout:
1. State the parental phenotypes
2. State the parental genotypes
3. Show the gametes (underline them or put them in circles)
4. Draw the Punnett square
5. State the offspring genotypes
6. State the offspring phenotypes AND the ratio

⭐ Cambridge Exam Tip — Always show all working

Example: Tall (T) is dominant over dwarf (t). Cross two heterozygous tall plants:
Parents: Tall × Tall
Genotypes: Tt × Tt
Gametes: T or t × T or t
Punnett square: TT, Tt, Tt, tt
Offspring genotypes: 1TT : 2Tt : 1tt
Offspring phenotypes: 3 tall : 1 dwarf
Always state BOTH the genotype ratio AND the phenotype ratio. Cambridge awards
separate marks for each.
4. Dihybrid Inheritance
Dihybrid inheritance involves TWO genes on DIFFERENT chromosomes (unlinked).
Because the genes assort independently (Mendel's Law of Independent Assortment), the
standard F2 ratio from a dihybrid cross is 9:3:3:1.

The 9:3:3:1 ratio breaks down as:

• 9 — dominant for both traits
• 3 — dominant for first trait, recessive for second
• 3 — recessive for first trait, dominant for second
• 1 — recessive for both traits

⭐ Cambridge Exam Tip — Dihybrid cross worked example

Round (R) is dominant over wrinkled (r). Yellow (Y) is dominant over green (y). Cross
two dihybrid peas (RrYy × RrYy):
Gametes from each parent: RY, Ry, rY, ry (four types)
Punnett square: 4×4 = 16 boxes
Expected ratio: 9 Round Yellow : 3 Round green : 3 wrinkled Yellow : 1 wrinkled green
Memorise this ratio — 9:3:3:1 is the standard dihybrid F2 ratio for unlinked,
independently assorting genes.

5. Codominance and Multiple Alleles

5.1 Codominance
In codominance, BOTH alleles are expressed in the heterozygote — neither is dominant
over the other. Use a notation where both alleles get superscripts.

Example — ABO blood groups (multiple alleles AND codominance):

• Three alleles exist: I^A, I^B, and i (lowercase i = recessive)
• I^A and I^B are CODOMINANT with each other — both expressed in the
heterozygote (I^A I^B = blood group AB)
• Both I^A and I^B are DOMINANT over i
 Genotype Blood group (phenotype) Antigens on red blood cells
I^A I^A or I^A i A A antigens only
I^B I^B or I^B i B B antigens only
I^A I^B AB Both A and B antigens —
codominance
ii O No A or B antigens

⭐ Cambridge Exam Tip — Blood group questions

Cambridge loves blood group questions. Common cross: blood group A (I^A i) × blood
group B (I^B i):
Gametes: I^A or i × I^B or i
Offspring: I^A I^B (AB), I^A i (A), I^B i (B), ii (O)
Ratio: 1 AB : 1 A : 1 B : 1 O — all four blood groups possible from this cross.
Model answer: "The parents are I^A i (blood group A) and I^B i (blood group B). The
gametes are I^A or i, and I^B or i. The possible offspring genotypes are I^A I^B (blood
group AB), I^A i (blood group A), I^B i (blood group B), and ii (blood group O), in a
1:1:1:1 ratio."

6. Sex Linkage
Sex-linked genes are carried on the sex chromosomes (X or Y). In humans, males are XY
and females are XX. Most sex-linked genes are on the X chromosome (X-linked) — the Y
chromosome carries very few genes.

Because males have only ONE X chromosome, they only have ONE allele for X-linked
genes — they are HEMIZYGOUS. A recessive X-linked allele will always be expressed in
males (no second allele to mask it).

Notation: write the allele as a superscript on the X. Example — red-green colour blindness:
• X^B = normal vision (dominant)
• X^b = colour blind (recessive)
• X^B X^B = normal vision female (homozygous dominant)
• X^B X^b = carrier female (heterozygous — normal phenotype but carries recessive
allele)
• X^b X^b = colour blind female (homozygous recessive)
• X^B Y = normal vision male
• X^b Y = colour blind male (hemizygous — only one allele, so it is expressed)
 ⭐ Cambridge Exam Tip — X-linked cross example
Cross: carrier female (X^B X^b) × normal male (X^B Y):
Gametes: X^B or X^b (female) × X^B or Y (male)
Offspring: X^B X^B (normal female), X^B X^b (carrier female), X^B Y (normal male), X^b
Y (colour blind male)
Ratio: 1:1:1:1 — but only males are affected. This is the KEY feature of X-linked
recessive conditions — males are affected more often than females.
Model answer: "Because males are hemizygous for X-linked genes, a single recessive
allele on the X chromosome is expressed. Females need two copies of the recessive
allele to show the phenotype. Therefore X-linked recessive conditions (e.g. haemophilia,
red-green colour blindness) affect males more frequently than females."

7. Autosomal Linkage
Autosomal linkage occurs when two genes are located on the SAME autosome (non-sex
chromosome). Linked genes tend to be inherited TOGETHER — they do not assort
independently.

If two genes are linked, the expected 9:3:3:1 dihybrid ratio is NOT obtained. Instead,
parental combinations appear more frequently and recombinant combinations less
frequently.

• PARENTAL COMBINATIONS — allele combinations as they exist in the parent.

These are the majority because linked genes stay together.
• RECOMBINANT COMBINATIONS — new combinations produced by crossing over
during meiosis. These are less frequent.

⭐ Cambridge Exam Tip — Identifying linkage from results

If a dihybrid cross gives results that deviate significantly from 9:3:3:1 — with parental
types more common than expected and recombinants rarer — the genes are likely to be
linked. Cambridge may give you data and ask you to suggest whether genes are linked.
Model answer: "The results deviate from the expected 9:3:3:1 ratio for independently
assorting genes. The parental combinations appear more frequently than expected, and
the recombinant combinations appear less frequently. This suggests that the two genes
are located on the same chromosome (autosomal linkage) and tend to be inherited
together. The recombinant types arise from crossing over between the two loci during
meiosis."
8. Epistasis
Epistasis: The interaction between two genes at different loci, where the alleles of one
gene mask or modify the expression of alleles at another gene. The masking gene is
said to be EPISTATIC to the masked gene.

Epistasis causes the standard 9:3:3:1 dihybrid ratio to be modified. Cambridge does NOT
require you to know the expected ratios for different types of epistasis — but you must
understand the concept and be able to explain results showing epistasis.

Example of epistasis — coat colour in Labrador dogs:

• Gene B controls pigment type: B (black) dominant over b (brown)
• Gene E controls pigment deposition: E allows pigment to be deposited (dominant).
ee = no pigment deposited → yellow coat regardless of B genotype
• So gene E is epistatic to gene B — ee masks the expression of B

Dihybrid cross BbEe × BbEe gives:

• 9 B_E_ = black (B dominant, E present — pigment deposited)
• 3 bbE_ = brown (bb, E present — brown pigment deposited)
• 3 B_ee = yellow (B present but ee — no pigment deposited)
• 1 bbee = yellow (bb and ee — no pigment deposited)
• Phenotype ratio = 9 black : 3 brown : 4 yellow — modified from 9:3:3:1

⭐ Cambridge Exam Tip — Explaining epistasis

Cambridge does not ask for specific epistasis ratios — but they DO ask you to explain
why results differ from 9:3:3:1:
Model answer: "The results show a modified ratio (9:3:4) rather than the expected
9:3:3:1 for two independently assorting genes. This indicates epistasis — one gene is
masking the expression of another. Individuals homozygous recessive for gene E (ee
genotype) cannot deposit any pigment, so they appear yellow regardless of their
genotype at the B locus. This means the ee genotype is epistatic to gene B, and the two
phenotypic classes that would be separate in a normal dihybrid cross are combined into
one class."
9. Test Crosses
A test cross crosses an individual showing the DOMINANT phenotype (unknown genotype
— could be AA or Aa) with a HOMOZYGOUS RECESSIVE individual (aa).

Unknown genotype Cross Offspring ratio Conclusion

AA (homozygous AA × aa All offspring show dominant If ALL offspring
dominant) phenotype (all Aa) show dominant
phenotype →
parent was
homozygous
dominant
Aa (heterozygous) Aa × aa 1 dominant : 1 recessive (Aa If offspring ratio is
: aa) 1:1 → parent was
heterozygous

⭐ Cambridge Exam Tip — Test cross question

Model answer: "A test cross involves crossing the organism with an unknown genotype
with a homozygous recessive individual. If all offspring show the dominant phenotype,
the unknown parent must be homozygous dominant (AA). If offspring appear in a 1
dominant : 1 recessive ratio, the unknown parent must be heterozygous (Aa). The
homozygous recessive parent contributes only recessive alleles, so any recessive
offspring must have received the recessive allele from the unknown parent — revealing
its genotype."

10. The Chi-Squared (χ²) Test

The chi-squared test is used to determine whether observed results differ significantly from
expected results. In genetics, it tests whether deviations from expected ratios are due to
chance or due to a real biological factor (e.g. linkage).

Null hypothesis: The assumption that there is NO significant difference between

observed and expected results — any deviation is due to chance alone.

Formula: χ² = Σ (O - E)² / E
Where O = observed frequency, E = expected frequency

How to carry out the chi-squared test:

7. State the null hypothesis: 'There is no significant difference between the observed
and expected results — any deviation is due to chance.'
 8. Calculate expected values — based on the predicted ratio × total number of offspring
9. Calculate (O - E)² / E for each class
10. Sum all values to get χ²
11. Calculate degrees of freedom: df = number of classes - 1
12. Look up the critical value at p = 0.05 in the chi-squared table
13. Compare χ² to the critical value:
◦ If χ² < critical value → ACCEPT null hypothesis. Difference is not significant.
Results fit the expected ratio.
◦ If χ² > critical value → REJECT null hypothesis. Difference IS significant. Results
do not fit the expected ratio.

⭐ Cambridge Exam Tip — Chi-squared worked example

Expected ratio 3:1. Total offspring = 160. Expected: 120 dominant : 40 recessive.
Observed: 110 dominant : 50 recessive.
χ² = (110-120)²/120 + (50-40)²/40 = 100/120 + 100/40 = 0.83 + 2.50 = 3.33
Degrees of freedom = 2 - 1 = 1. Critical value at p=0.05, df=1 = 3.84
3.33 < 3.84 → Accept null hypothesis. The difference is not significant. Results are
consistent with a 3:1 ratio.
Model answer: "The null hypothesis states there is no significant difference between the
observed and expected results. The calculated chi-squared value (3.33) is less than the
critical value (3.84) at p = 0.05 with 1 degree of freedom. Therefore we accept the null
hypothesis — the deviation from the expected 3:1 ratio is due to chance and the results
are consistent with monohybrid inheritance."

11. Genes, Proteins and Phenotype

The syllabus requires you to explain the relationship between genes, proteins and
phenotype for four specific examples:

Gene Protein Phenotype when gene mutated

TYR gene Tyrosinase — enzyme that Albinism — no melanin produced. White hair, pink
catalyses melanin eyes, pale skin.
production
HBB gene Beta globin chain of Sickle cell anaemia — single base substitution
haemoglobin (GAG→GTG) changes glutamic acid to valine in
the beta chain. Haemoglobin S forms fibres when
deoxygenated — red blood cells become sickle-
shaped.
F8 gene Factor VIII — a clotting Haemophilia A — blood cannot clot properly. X-
factor in the blood linked recessive condition.
HTT gene Huntingtin — a protein Huntington's disease — dominant mutation.
 involved in nerve function Repeated CAG triplets → abnormal huntingtin
protein. Progressive neurodegeneration. Late
onset (40-50 years).

⭐ Cambridge Exam Tip — Sickle cell anaemia is a key example

Cambridge uses sickle cell anaemia to illustrate multiple concepts: gene mutation,
protein structure, phenotype, natural selection (heterozygote advantage in malaria-
endemic regions). Know it in detail:
• Cause: single base substitution in the HBB gene (6th codon: GAG → GTG)
• Result: glutamic acid replaced by valine in the beta globin chain
• Effect: haemoglobin S (HbS) — when deoxygenated, HbS molecules stick
together forming fibres
• Sickle-shaped red blood cells block capillaries, cause pain crises, anaemia
• Heterozygotes (HbA/HbS) have some protection against malaria — natural
selection maintains HbS allele in malaria-endemic populations
Model answer: "Sickle cell anaemia is caused by a single base substitution in the HBB
gene, changing the sixth codon from GAG to GTG. This causes glutamic acid to be
replaced by valine in the beta globin polypeptide chain. The resulting haemoglobin S
forms fibres when deoxygenated, distorting red blood cells into a sickle shape. These
cells block blood vessels, causing pain and tissue damage, and are destroyed more
quickly, causing anaemia."

11.1 Gibberellin and Stem Elongation — Gene Control

The syllabus includes the role of the Le and le alleles in pea stem elongation as an example
of gene-protein-phenotype relationships:
• Le allele (dominant) — codes for a FUNCTIONAL enzyme in the gibberellin synthesis
pathway → gibberellin is produced → stems elongate normally → TALL plants
• le allele (recessive) — codes for a NON-FUNCTIONAL enzyme → gibberellin is not
produced → stems do not elongate → DWARF plants
• This was one of Mendel's original pea plant traits — it is now explained at the
molecular level

12. Gene Control

12.1 Structural Genes vs Regulatory Genes

Type Definition Example
Structural gene A gene that codes for a protein with a Gene coding for beta-
 structural or enzymatic role in the cell galactosidase in the lac operon
Regulatory gene A gene that codes for a regulatory protein The lacI gene — codes for the
(e.g. repressor) that controls the lac repressor protein
expression of other genes

12.2 Inducible vs Repressible Enzymes

Type Definition Example
Inducible enzymes Enzymes that are produced only when Beta-galactosidase in E. coli —
their substrate (inducer) is present. The only produced when lactose is
inducer prevents the repressor from present
blocking transcription.
Repressible Enzymes that are produced constitutively Tryptophan biosynthesis
enzymes (all the time) but are switched off when the enzymes — switched off when
end product of their pathway accumulates tryptophan levels are high
(corepressor binds to repressor).

12.3 The Lac Operon

The lac operon is a cluster of genes in E. coli that controls lactose metabolism. It is a classic
example of gene control in prokaryotes.

When lactose is ABSENT:

14. The regulatory gene (lacI) is always transcribed → repressor protein is made
15. The repressor protein binds to the OPERATOR region of the operon
16. RNA polymerase cannot move past the operator → transcription of structural genes
is BLOCKED
17. No beta-galactosidase is produced — no need to make it when lactose is absent

When lactose is PRESENT:

18. Lactose (inducer) enters the cell and is converted to allolactose
19. Allolactose binds to the repressor protein → changes its shape (conformational
change)
20. The repressor can no longer bind to the operator — it detaches
21. RNA polymerase can now transcribe the structural genes (lacZ, lacY, lacA)
22. Beta-galactosidase and permease are produced → lactose is broken down

⭐ Cambridge Exam Tip — Lac operon is about INDUCTION not always-on

Model answer: "In the absence of lactose, the repressor protein binds to the operator
region and prevents RNA polymerase from transcribing the structural genes, including
the gene for beta-galactosidase. When lactose is present, allolactose (derived from
lactose) binds to the repressor, causing a conformational change that prevents it from
binding to the operator. RNA polymerase can now transcribe the structural genes,
 producing beta-galactosidase, which breaks down lactose. This is an example of an
inducible system — the enzyme is only produced when its substrate is available."

12.4 Transcription Factors in Eukaryotes

• Transcription factors are PROTEINS that bind to specific DNA sequences near
genes and either INCREASE or DECREASE the rate of transcription
• They allow precise control of which genes are expressed in which cells and at which
times
• Example: gibberellin causes breakdown of DELLA repressor proteins → transcription
factors can now promote transcription (covered in Topic 15)

13. Worked Exam Questions

Q1 — Dihybrid cross with codominance (challenging question)

'In cattle, coat colour is controlled by two codominant alleles: C^R (red) and C^W (white).
Heterozygotes are roan (mixture of red and white hairs). Horns are controlled by a separate
gene: H (horned) is dominant over h (hornless). A roan horned bull is crossed with a white
hornless cow. State the possible phenotypes and their ratios.' [4 marks]

⭐ Model Answer
Bull genotype: C^R C^W Hh. Cow genotype: C^W C^W hh.
Gametes from bull: C^R H, C^R h, C^W H, C^W h. Gametes from cow: C^W h only.
Offspring genotypes: C^R C^W Hh (roan horned), C^R C^W hh (roan hornless), C^W
C^W Hh (white horned), C^W C^W hh (white hornless)
Phenotype ratio: 1 roan horned : 1 roan hornless : 1 white horned : 1 white hornless
Note: No red offspring are possible because the cow contributes no C^R allele. (4 marks
— 1 for each correct phenotype identified with correct ratio)

Q2 — Chi-squared test (Paper 4 question)

'A student crossed two dihybrid plants and obtained 180 offspring: 98 tall yellow, 34 tall
green, 32 short yellow, 16 short green. Use chi-squared to test whether these results fit a
9:3:3:1 ratio.' [5 marks]
 ⭐ Model Answer
Null hypothesis: There is no significant difference between observed and expected
results — any deviation is due to chance.
Total = 180. Expected ratio 9:3:3:1 = 9/16 × 180 = 101.25 : 3/16 × 180 = 33.75 : 33.75 :
1/16 × 180 = 11.25
χ² = (98-101.25)²/101.25 + (34-33.75)²/33.75 + (32-33.75)²/33.75 + (16-11.25)²/11.25
= 0.10 + 0.002 + 0.09 + 2.01 = 2.20
df = 4-1 = 3. Critical value at p=0.05, df=3 = 7.82.
2.20 < 7.82 → Accept null hypothesis. Results are consistent with a 9:3:3:1 ratio.
Deviation is due to chance.

14. Revision Checklist

Topic Tick when
confident
Define all 14 key terms precisely — gene, locus, allele, dominant, recessive,
codominant, genotype, phenotype, homozygous, heterozygous, linkage, F1,
F2, test cross
Explain how crossing over and independent assortment during meiosis
generate genetic variation
Carry out monohybrid crosses in Cambridge format — phenotypes,
genotypes, gametes, Punnett square, ratios
State the expected F2 ratio from Aa × Aa (3:1) and test cross Aa × aa (1:1)

Carry out dihybrid crosses — state the expected 9:3:3:1 ratio for unlinked
genes
Explain codominance with reference to ABO blood groups — use correct
notation
Carry out blood group crosses using I^A, I^B, i notation

Explain sex linkage — why males are hemizygous; why X-linked recessive
conditions affect males more
Carry out X-linked crosses using correct X^B, X^b, Y notation

Explain autosomal linkage — how it modifies the 9:3:3:1 ratio

Define epistasis and explain how it modifies dihybrid ratios with an example

Describe the test cross and interpret results to determine unknown genotype

State the null hypothesis for chi-squared; carry out chi-squared calculation;
interpret result
Explain the gene-protein-phenotype relationship for TYR/albinism,
HBB/sickle cell, F8/haemophilia, HTT/Huntington's
Explain the molecular basis of sickle cell anaemia — base substitution,
amino acid change, haemoglobin S
Explain the Le/le alleles and gibberellin synthesis in pea stem elongation

Distinguish structural genes and regulatory genes; inducible and repressible

enzymes
Describe the lac operon — how it works in the presence and absence of
lactose
Explain the role of transcription factors in eukaryote gene control

Topic 16 is the calculation engine of A Level Biology. Practice crosses until

they are automatic. The definitions are the foundation — if you know them
precisely, the rest follows.