IMAT Biology · Genetics and Inheritance

Sex Chromosomes, the SRY Gene and X-linked Inheritance

Sex in humans is set by the sex chromosomes, and genes on the X chromosome follow special rules because a male has only one X.

All Genetics and Inheritance notes

Why this matters

This is the most asked part of the chapter. Haemophilia crosses came up in 2011 and 2022, an X-linked dominant condition in 2018, the SRY gene in 2021, and the 2023 ministry paper asked twice: which statement about an X-linked recessive muscle disease is wrong, and which colour-blindness families can have an affected daughter.

Concept 1 of 3: Sex determination in humans: XX, XY and the SRY gene

Every egg carries an X chromosome. A sperm carries either an X or a Y, in equal numbers, so the sperm decides the sex. What makes an embryo male is not the Y as a whole but one gene on it, SRY, which switches on testis development. The testes then make the hormones that build the rest of the male body.

Definition

Human body cells have 46 chromosomes: 22 pairs of autosomes and one pair of sex chromosomes. Females are XX, males XY.
Gametes carry 23: 22 autosomes plus one sex chromosome. Eggs always carry X; sperm carry X or Y in a 1 : 1 ratio, so $P(\text{boy}) = \tfrac12$ for each child.
The SRY gene (sex-determining region of Y) starts testis development. Without it, the embryo develops as female.
The X carries many genes (hundreds that code for proteins); the Y carries few. A male has one copy of each X gene: he is hemizygous.
In females one X in each body cell is switched off at random early in development (X inactivation, seen as a Barr body). Tortoiseshell cats show the resulting patches.

Situation	Sex that develops	Reason
XX	Female	No SRY gene
XY	Male	SRY on the Y starts testis development
XX with SRY moved onto one X	Male	SRY is present, even without a Y
XY with SRY lost or not working	Female	No working SRY
XXY	Male	One Y with SRY is enough

SRY can move onto an X by an abnormal crossover in the father's meiosis, giving an X-bearing sperm that makes a male.

Practice this conceptself-check · 4 quick reps

It is SRY, not the Y chromosome as a whole, that makes a male

An XX person carrying SRY on one X develops as a male, and an XY person without a working SRY develops as a female. Statements that tie maleness only to "having a Y" miss this.

Concept 2 of 3: X-linked recessive inheritance: haemophilia, colour blindness, Duchenne

A woman has two X chromosomes, so a recessive allele on one X is usually masked by a normal allele on the other: she is a carrier. A man has only one X, with nothing to mask it, so one recessive allele is enough. That is why these conditions are far more common in men, and why a son always gets his X from his mother.

Definition

Write the alleles on the X: $X^H$ normal, $X^h$ affected; the Y carries no allele.

Female genotypes: $X^H X^H$ normal, $X^H X^h$ carrier (normal phenotype), $X^h X^h$ affected.
Male genotypes: $X^H Y$ normal, $X^h Y$ affected. One allele decides.
A father gives his X to every daughter and his Y to every son: an affected man has all daughters carriers and no affected sons through him.
A carrier mother gives the allele to half her children: half her sons are affected, half her daughters are carriers.
An affected woman needs an affected father and a carrier (or affected) mother; all her sons are affected.
Examples: haemophilia A (no clotting factor VIII), red-green colour blindness, Duchenne muscular dystrophy (faulty dystrophin). The allele spreads in a population with the X chromosomes that carry it.

Carrier mother and unaffected father

X^H X^h \times X^H Y \rightarrow \tfrac14 X^H X^H + \tfrac14 X^H X^h + \tfrac14 X^H Y + \tfrac14 X^h Y

$X^h$ X chromosome carrying the recessive allele
$Y$ Y chromosome, carrying no allele of this gene

Worked example

A man with haemophilia (

X^h Y

) has children with a woman who is homozygous normal (

X^H X^H

). (a) Describe their sons and daughters. (b) One of their daughters later has children with an unaffected man. What fraction of her sons will be affected, and what is the probability that any one of her children is an affected son?

Practice this conceptself-check · 4 quick reps

A father never passes an X-linked allele to his son

Sons receive their father's Y. So an affected son of an unaffected father got the allele from his mother, and an affected father cannot have an affected son through his own X. Any option tracing an X-linked allele from father to son is wrong.

"Half the sons" is not "a quarter of the children"

For a carrier mother and a normal father,

\tfrac12

of the sons are affected, but only

\tfrac14

of all children are affected sons. Women are affected far less often than men, never more often, for a recessive X-linked allele.

Concept 3 of 3: X-linked dominant and Y-linked inheritance

For an X-linked dominant allele, one copy causes the condition in either sex. The same rule as before decides who gets it: a father's X goes to all his daughters and to none of his sons. A Y-linked gene is simpler still: only men have a Y, and every son gets his father's Y.

Definition

X-linked dominant (e.g. X-linked hypophosphataemic rickets): an affected man ( $X^R Y$ ) has all daughters affected and no sons affected.
A heterozygous affected woman ( $X^R X^r$ ) passes it to half her children of either sex.
An affected boy must have an affected mother. An affected girl has at least one affected parent.
More females than males are affected (females have two chances to receive the allele).
Y-linked (e.g. SRY, some male-infertility genes): only males, passed from father to every son, never to daughters.

Affected father, X-linked dominant

X^R Y \times X^r X^r \rightarrow \text{daughters all } X^R X^r,\ \text{sons all } X^r Y

$X^R$ X carrying the dominant allele that causes the condition
$X^r$ X carrying the normal recessive allele

Worked example

An X-linked dominant condition. (a) An affected heterozygous woman has children with an unaffected man: what is the chance that a daughter is affected, and that a son is affected? (b) An affected man has children with an unaffected woman: describe the children.

Practice this conceptself-check · 3 quick reps

An X-linked allele in a boy came from his mother

Whether the X-linked allele is dominant or recessive, a boy's only X came from his mother. If he has an X-linked dominant condition, his mother must carry the allele, and since it is dominant she is affected too. His father is irrelevant to it.

Summary — formulas & gotchas at a glance

A revision cheat-sheet for the formulas and gotchas above. Click any concept name to jump back to its full explanation.

Formulas (2)

X-linked recessive inheritance: haemophilia, colour blindness, Duchenne
Carrier mother and unaffected father
$X^H X^h \times X^H Y \rightarrow \tfrac14 X^H X^H + \tfrac14 X^H X^h + \tfrac14 X^H Y + \tfrac14 X^h Y$
X-linked dominant and Y-linked inheritance
Affected father, X-linked dominant
$X^R Y \times X^r X^r \rightarrow \text{daughters all } X^R X^r,\ \text{sons all } X^r Y$

Reference tables (1)

Sex determination in humans: XX, XY and the SRY gene5 rows

Situation	Sex that develops	Reason
XX	Female	No SRY gene
XY	Male	SRY on the Y starts testis development
XX with SRY moved onto one X	Male	SRY is present, even without a Y
XY with SRY lost or not working	Female	No working SRY
XXY	Male	One Y with SRY is enough

SRY can move onto an X by an abnormal crossover in the father's meiosis, giving an X-bearing sperm that makes a male.

Watch out for (4)

It is SRY, not the Y chromosome as a whole, that makes a male
→ Sex determination in humans: XX, XY and the SRY gene
A father never passes an X-linked allele to his son
→ X-linked recessive inheritance: haemophilia, colour blindness, Duchenne
"Half the sons" is not "a quarter of the children"
→ X-linked recessive inheritance: haemophilia, colour blindness, Duchenne
An X-linked allele in a boy came from his mother
→ X-linked dominant and Y-linked inheritance

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