Sex-linked inheritance explained: HSC Biology Module 5

Top marks (4) require explaining the possible outcomes of the cross AND relating differences in those outcomes to justify the type of inheritance, communicated succinctly with appropriate terms/formats (e.g. Punnett squares).

Sample answer (marking guidelines):

• If sex-linked: I and II would be X^A Y and X^a X^a respectively. The cross would produce all male offspring yellow and all female offspring orange.
• If autosomal: II would be aa, while I would be AA or Aa. If I is AA all offspring are orange; if I is Aa, then 50% of offspring would be yellow and 50% orange, with colours distributed equally between male and female offspring.
• Therefore, the absence of any orange male offspring from this cross would confirm the inheritance is sex-linked.

Markers noted poor use of Punnett-square format and limited understanding of the difference between autosomal and sex-linked inheritance.

Source: NESA 2020 HSC Biology examination and marking guidelines.

Carrier (1 mark). A carrier is an individual who has one copy of a recessive allele but does not express the trait because a dominant allele masks it. For an X-linked recessive trait, a carrier is a heterozygous female ($X^H X^h$) who is phenotypically unaffected but can pass the allele to her offspring.

Sex-linked (1 mark). A sex-linked trait is controlled by a gene located on a sex chromosome (almost always the X chromosome in HSC examples), so its inheritance pattern differs between males and females.

Parental genotypes (1 mark)

Mother $X^H X^H$ (unaffected non-carrier); father $X^h Y$ (affected).

Daughters (1 mark)

Every daughter inherits her father's only X (the $X^h$) and one of her mother's $X^H$ alleles, so all daughters are $X^H X^h$, that is, unaffected carriers.

Sons (1 mark)

Every son inherits his father's Y and one of his mother's $X^H$ alleles, so all sons are $X^H Y$, that is, unaffected.

No children are affected in this cross; the key teaching point is that an affected father passes the allele to all daughters but to none of his sons.

Punnett square (1 mark)

Mother gametes $X^H$ and $X^h$; father gametes $X^H$ and Y. Offspring: $X^H X^H$, $X^H X^h$, $X^H Y$, $X^h Y$.

Sons (1 mark)

Sons are $X^H Y$ or $X^h Y$ in equal proportion, so $\tfrac{1}{2}$ (50%) of sons are affected.

Daughters (1 mark)

Daughters are $X^H X^H$ or $X^H X^h$ in equal proportion. No daughter is affected (0%), and $\tfrac{1}{2}$ (50%) of daughters are carriers.

Affected males (1 mark)

A male is affected if his single X carries the recessive allele, so the male incidence equals the allele frequency: $q = 0.08$, that is, 8%.

Affected females (1 mark)

A female is affected only if BOTH X chromosomes carry the recessive allele, so the female incidence equals $q^2 = 0.08^2 = 0.0064$, that is, 0.64%.

Explanation (2 marks)

Award 1 mark for stating that males are hemizygous (only one X), so a single recessive allele is enough to make a male affected, whereas a female needs two. Award the second mark for linking this to the maths: requiring two independent copies multiplies the probability ($q \times q = q^2$), which for a small $q$ is far smaller than $q$ itself, so affected females are much rarer than affected males.

Part (a) - parents (2 marks). The father is unaffected, so he is $X^H Y$ (1 mark). The mother is unaffected but has an affected son, who must have inherited his $X^h$ from her, so she must carry one $X^h$; being unaffected she is the heterozygous carrier $X^H X^h$ (1 mark).

Part (b) - daughter (2 marks). From the cross $X^H X^h \times X^H Y$, daughters are $X^H X^H$ or $X^H X^h$ in a $1:1$ ratio, and BOTH are unaffected (1 mark). The daughter is known to be unaffected, but all daughters of this cross are unaffected, so this gives no extra information; the conditional probability that she is a carrier is therefore $\tfrac{1}{2}$, that is, 50% (1 mark).

Punnett square (2 marks)

Female gametes $X^O$ and $X^o$; male gametes $X^o$ and Y. Offspring: $X^O X^o$, $X^o X^o$, $X^O Y$, $X^o Y$ (1 mark for correct gametes, 1 mark for correct cells).

Genotypic ratio (1 mark)

$1\ X^O X^o : 1\ X^o X^o : 1\ X^O Y : 1\ X^o Y$.

Phenotypic ratio (1 mark)

Daughters: $\tfrac{1}{2}$ carrier (unaffected), $\tfrac{1}{2}$ affected. Sons: $\tfrac{1}{2}$ unaffected, $\tfrac{1}{2}$ affected. Overall $\tfrac{1}{4}$ of offspring are affected daughters and $\tfrac{1}{4}$ are affected sons.

Affected daughters (1 mark)

A carrier mother crossed with an AFFECTED father ($X^o Y$) is the only standard X-linked recessive cross that can produce affected daughters, because a daughter needs a recessive allele from BOTH parents and only an affected father supplies an $X^o$ to every daughter.

The decisive cross (1 mark)

Cross an affected female with an unaffected (wild-type) male. This reciprocal cross is decisive because the outcome differs sharply depending on whether the gene is on the X chromosome or an autosome.

If X-linked recessive (2 marks)

Affected female is $X^a X^a$; unaffected male is $X^A Y$. Every son inherits his mother's $X^a$ and his father's Y, so ALL sons are $X^a Y$ (affected). Every daughter inherits her mother's $X^a$ and her father's $X^A$, so ALL daughters are $X^A X^a$ (unaffected carriers). Prediction: all sons affected, all daughters unaffected - a clear sex difference (criss-cross inheritance).

If autosomal recessive (2 marks)

Affected female is $aa$; unaffected male is $AA$ (or $Aa$). If the male is $AA$, all offspring are $Aa$ and unaffected, with no difference between sexes. If the male is $Aa$, half the offspring are affected, again with no difference between the sexes.

Decision rule (1 mark)

If the trait appears in ALL the sons but NONE of the daughters (a sex-linked difference), the gene is X-linked recessive. If the affected and unaffected offspring are distributed equally between the sexes, it is autosomal. Award full marks only where the candidate states the test cross, gives both predictions with correct notation, and links the observed sex pattern to a decision.

Restating and supporting the claim (2 marks)

A father passes his Y chromosome (not his X) to every son, so an affected father ($X^h Y$) gives each son a Y and the son's single X comes from the mother. Modelling $X^h Y \times X^H X^H$: sons are $X^H Y$ (all unaffected) and daughters are $X^H X^h$ (all carriers). The father's affected allele therefore reaches his daughters, never his sons - supporting the claim for father-to-son transmission of the allele itself.

The carrier state and how a son CAN be affected (2 marks)

A son becomes affected only by inheriting $X^h$ from his MOTHER. If the mother is a carrier ($X^H X^h$), modelling $X^H X^h \times X^H Y$ gives sons $X^H Y$ and $X^h Y$ in a $1:1$ ratio, so half the sons are affected. The allele a father passes to his daughters can re-emerge in his GRANDSONS, because those carrier daughters can pass $X^h$ to their own sons (the criss-cross pattern).

Evaluating the limits (2 marks)

The claim is true for the direct father-to-son step of the SAME allele, because of Y-only transmission to sons. It is misleading if read as "the disorder cannot run in the male line," because it reappears in grandsons via carrier daughters. The claim also assumes standard X-linkage; it would not hold for an autosomal or Y-linked trait, or in the rare case of a son who is affected by a new mutation.

Communication (1 mark)

Awarded for a sustained, logically sequenced judgement that uses correct $X^H$/$X^h$/Y notation and at least one correct Punnett square to support each part of the evaluation.