Key points:

 In humans and other mammals, biological sex is determined

by a pair of sex chromosomes: XY in males and XX in
females.
 Genes on the X chromosome are said to be X-linked. X-
linked genes have distinctive inheritance patterns because
they are present in different numbers in females (XX) and
males (XY).
 X-linked human genetic disorders are much more common
in males than in females due to the X-linked inheritance
pattern.

Introduction

If you’re a human being (which seems like a good bet!), most

of your chromosomes come in homologous pairs. The two
chromosomes of a homologous pair contain the same basic
– that is, the same genes in the same order – but may carry
different versions of those genes.

Are all of your chromosomes organized in homologous

pairs? The answer depends on whether you’re
(chromosomally) male.
 A human male has two sex chromosomes, the X and the Y.
Unliked the 44 autosomes (non-sex chromosomes), the X
and Y don’t carry the same genes and aren’t considered
homologous.
 Instead of an X and a Y, a female has two X chromosomes.
These X chromosomes do form a bona fide homologous
pair.

Because sex chromosomes don’t always come in

homologous pairs, the genes they carry show unique,
distinctive pairs, the genes they carry show unique,
distinctive patterns of inheritance.

Sex chromosomes in humans

Human X and Y chromosomes determine the biological sex

of a person, with XX specifying female and XY specifying
male. Although the Y chromosome contains a small region of
similarity to the X chromosome so that they can pair during
meiosis, the Y chromosome is much shorter and contains
many fewer genes.

To put some numbers to it the X chromosome has about 800

– 900 protein-coding genes with a wide variety of functions,
while the Y chromosome has just 60 – 70 protein-coding
genes, about half of which are active only in the testes
(sperm-producing organs).
The human Y chromosome plays a key role in determining
the sex of a developing embryo. This is mostly due to a gene
called SRY (“sex-determining region of Y”). SRY is found on
 the Y chromosome and encodes a protein that turns on other
genes required for male development.

 XX embryos don’t have SRY, so they develop as female.

 XY embryos do have SRY, so they develop as a male.

In rare cases, errors during meiosis may transfer SRY from

the Y chromosome to the X chromosome. If an SRY-bearing
X chromosome fertilizes a normal egg, it will produce a
chromosomally female (XX) embryo that develops as a
male. If an SRY-bearing X chromosome fertilizes a normal
egg, it will produce a chromosomally female (XX) embryo
that develops as a male. If an SRY-deficient Y chromosome
fertilizes a normal egg, it will produce a chromosomally male
embryo (XY) that develops as a female.

X-linked genes

When a gene is present on the X chromosome, but not on

the Y chromosome, it is said to be X-linked. X-linked genes
have different inheritance patterns than genes on non-sex
chromosomes (autosomes). That’s because these genes are
present in different copy numbers in males and females.

Since a female has two X chromosomes, she will have two

copies of each X-linked gene. For instance, in the fruit fly
Drosophila (which, like humans, has XX females and XY
males), there is a eye color gene called white that’s found on
the X chromosome, and a female fly will have two copies of
this gene. If the gene comes in two different alleles, such as
X^W (dominant, normal red eyes) and X^w (recessive, white
eyes), the female fly may have any of three genotypes: X^W
X^W (red eyes), X^W X^w (red eyes), and X^w X^w (white
eyes).

A male has different genotype possibilities than a female.

Since he has only one X chromosome (paired with a Y), he
will only have one copy of any X-linked genes. For instance,
in the fly eye color example, the two genotypes a male can
have are X^W Y (red eyes) and X^w Y (white eyes).
Whatever allele the male fly inherits for an X-linked gene will
determine his appearance, because he has no other gene
copy – even if the allele is recessive in females. Rather than
homozygous or heterozygous, males are said to be
hemizygous for X-linked genes.

We can see how sex linkage affects inheritance patterns by

considering a cross between two flies, a white-eyed female
(X^w X^w) and a red-eyed male (X^W Y). If this gene were
on a non-sex chromosome, or autosome, we would expect
all of the offspring to be red-eyed, because the red allele is
dominant to the white allele. What we actually see is the
following:
However, because the gene is X-linked, and because it was
the female parent who had the recessive phenotype (white
eyes), all the male offspring – who get their only X from their
mother – have white eyes (X^w Y). All the female offspring
have red eyes because they received two Xs, with the X^W
from the father concealing the recessive X^w from the
mother.

X-linked genetic disorders

The same principles we see at work in fruit flies can be

applied to human genetics. In humans, the alleles for certain
conditions (including some forms of color blindness,
haemophilia, and muscular dystrophy) are X-linked. These
diseases are much more common in men than they are in
women due to their X-linked inheritance pattern.

Why is this the case? Let’s explore this using an example in

which a mother is heterozygous for a disease-causing allele.
Women who are heterozygous for disease alleles are said to
be carriers, and they usually don’t display any symptoms
themselves. Sons of these women have a 50% chance of
getting the disorder, but daughters have little chance of
getting the disorder (unless the father also has it), and will
instead have a 50% chance of being carriers.
Why is this the case? Recessive X-linked traits appear more
often in males than females because, if a male receives a
“bad” allele from his mother, he has no chance of getting a
“good” allele from his father (who provides a Y) to hide the
bad one. Females, on the other hand, will often receive a
normal allele from their fathers, preventing the disease allele
from being expressed.

Case study: Hemophilia

Let’s look at a Punnett square example using an X-linked

human disorder: hemophilia, a recessive condition in which a
person’s blood does not clot properly. A person with
hemophilia may have sever, even life-threatening bleeding
from just a small cut.

Hemophilia is caused by a mutation in either of two genes,

both of which are located on the X chromosome. Both genes
encode proteins that help blood clot. Let’s focus on just one
of these genes, calling the functional allele X^H and the
disease alle X^h.

In our example, a woman who is heterozygous for normal

and hemophilia alleles (X^H X^h) who is heterozygous for
the normal form (X^H Y). Both parents have normal blood
clotting, but the mother is a carrier. What is the chance of
their sons and daughters having hemophilia?
 Since the mother is a carrier, she will pass on the hemophilia
allele (X^h) on to half of her children, both boys and girls.

 None of the daughters will have hemophilia (zero chance of

the disorder). That’s because, in order to have the disorder,
they must get a X^h allele from both their mother and their
father. There is 0 chance of the daughters getting an X^h
allele from their father, so their overall chance of having
hemophilia is zero.
 The sons get a Y from their father instead of an X, so their
only copy of the blood clotting gene comes from their
mother. The mother is heterozygous, so half of the sons, on
average, will get an X^h allele and have hemophilia (50%
chance of the disorder).