SEX LINKAGE

Characters which are associate more

with one gender
Sex Determination

 What are the

X Y
odds of getting a
male? A female?
⚫ 50/50 X XX XY

X XX XY
What is it?

 Sex Linkage is the phenotypic

expression of an allele that is related
to the chromosomal sex of an
individual

 Since there are far more genes on the

X chromosome than the Y, there are
far more X linked traits that Y linked
traits
What’s the Comparison
Like?
Mode of Inheritance
 This mode of inheritance is in
contrast to the inheritance of
traits on autosomal
chromosomes
 What does autosomal mean?
⚫ An autosome is a non-sex
chromosome
⚫ It is an ordinarily paired chromosome
that is the same in both sexes of a
species
Mode of Inheritance

 Non-autosomal chromosomes are

usually referred to as sex
chromosomes, allosomes or
heterosomes

 In contrast to normal autosomal

chromosomes, both sexes do not
have the same probability of
expressing the trait
 Why does this happen?
 In mammals the female is said to be
homogametic where as the male is said to be
heterogametic.
 What does homogametic mean?
⚫ It means that there are two of the same
chromosomes (ie., X X)
 What does heterogametic mean?
⚫ It means that there are two different
chromosomes (ie., X Y)
Why does this happen?

 The genes that are present on the X

or Y chromosomes are called sex
linked genes

 Now, the chromosomes of interest still

have genes and alleles, and these
alleles are passed on to their progeny
Why does this happen?

 These traits are also, as we

discussed, dominant and recessive

 It can be said that X-linked recessive

traits are expressed in all
heterogametics, and in homogametics
that are homozygous for the recessive
allele
Well what does this mean?

 Heterogametics only have one X

chromosome, and therefore what ever
is there is expressed (ie., it can not be
masked by the other chromosome)

 Homogametics on the other hand

must have both chromosomes
affected for the X linked recessive
chromosome to have an effect
 Homogametic

Heterogametic
So what do you think?
 Which of the two, homogametic
or heterogametic, do you think
will have expression of the
genetic disorders more often?

 Think to yourself, share with a

friend, and then lets have a
class discussion and make sure
that your answer makes sense
Males get the short end of the
Stick
 Males, or heterogametics have a
higher incidence of expression
because of the fact that there is no
other allele to mask the damaged one

 If this is the case, all males that get

the gene or allele that codes for the
damaged expression will express to
the fullest extent
So that’s the male, what
about the female?
 What are the possibilities for the
female?
⚫ Is it possible for the female to express
the same way that the male does?
• Yes, of course, but there is a stipulation
• The female must contain two damaged
alleles (chromosomes) in order to express
 But hold on, what does this mean for
the female with regards to passing on
her genes?
What can she be?

 She can actually be a carrier

 What is a carrier?
⚫ A carrier is an individual that has two
alleles, one damaged one and one
regular
⚫ Their phenotypes are the same as a
regular individual
⚫ But their genes hold a “secret”
Back to men

 Can a man be a carrier?

⚫ Think about it for a few minutes with a
partner, and really think hard about it
⚫ For X linked alleles, no it is not
possible

 Why?
What kind of progeny would
we expect?
 The progeny
 We saw in the last photo that you can get
normal males and females if the mother is a
carrier, and you can also get carrier females
and affected sons

 Why can you not get affected females?

⚫ There is no affected X that comes from the
father
⚫ The only way to get an affected female is if
there is an affected male and a carrier or
affected female
An Example

 Red/Green Colour blindness

 This is a recessive X linked

 When passed on to males, they are

automatically colour blind to red and
green, females can be carriers or can
be colour blind
 Linked genes

 Genes for different characters inherited

as if they were a single character
 These genes are called LINKED GENES

 That is the LOCI for these genes are

linked on the same chromosome.

© 2016 Paul Billiet ODWS

 Characters associated with
gender
Anhiorotic ectodermal dysplasia
 Small teeth, no sweat glands, sparse
body hair
 Occurs primarily in men

 Never transmitted from father to son

 Unaffected daughters may pass the

condition onto their sons (the
grandsons).

© 2016 Paul Billiet ODWS

 EXAMPLE PROBLEM:
● A female heterozygous for normal vision:
(we say she has normal vision,
but is a carrier of the colorblindness allele)

XC Xc
● A male who is colorblind:

Xc Y
 What is the probability that:

a) they will have a son who is colorblind?

b) they will have a daughter who is colorblind?

c) their first son will be colorblind?

d) their first daughter will be carrier?

What is the probability that:
a) they will have a son who is colorblind?

b) they will have a daughter who is colorblind?

c) their first son will be colorblind?

d) their first daughter will be carrier?

XC Xc a) 1/4 (25%)

X
b) 1/4 (25%)
c XC Xc Xc Xc
c) 1/2 (50%)

Y XC Y Xc Y
d) 1/2 (50%)
 X-linked genes
 In sex linked characteristics the reciprocal crosses
do not give the same results
 For X-linked genes fathers do not pass the mutant
allele onto their sons
 For X-linked genes fathers pass the mutant allele
onto their daughters who are carriers
 Carrier mothers may pass the allele onto their sons
(50% chance)
 Females showing the trait for an X-linked mutant
allele can exist but they are rare
 Female carriers may show patches of cells with
either trait due to X chromosome inactivation.
© 2016 Paul Billiet ODWS
 X-inactivation in Female
Mammals
● In mammalian females, one of the two X
chromosomes in each cell is randomly
inactivated during embryonic development
● If a female is heterozygous for a particular
gene located on the X chromosome, she
will be a mosaic for that character
 Two cell populations
in adult cat:

Active X

Early embryo: Orange

X chromosomes fur
Cell division
Inactive X
and X
chromosome Inactive X
inactivation
Allele for Black
orange fur fur

Allele for Active X

black fur
Tortoise-shell cats!
(a.k.a. “Torties”)

XBXb
Tortioseshell
Cats are
Female

© 2016 Paul Billiet ODWS

 Daltonism = Red-Green
Colourblindness

Normal vision Colour blind simulation

www.onset.unsw.edu.au/.../colourblindness.htm
© 2016 Paul Billiet ODWS
 Blood Clotting and Hemophilia

A simplified scheme of the important steps

Damaged blood vessels

Prothrombin Thrombin
Inactive enzyme Active enzyme

Fibrinogen Fibrin = Clot

Globular protein Fibrous protein
© 2016 Paul Billiet ODWS
 Contact with collagen fibres
in blood vessels
Factor III
Thromboplastin released
from blood vessel walls
Factor XII (inactive) → Factor XII (active)

Factor XI (inactive) → Factor XI (active)

Factor IX (inactive) → Factor IX (active)

Antihemophilic factor B
Factor VIII
Antihemophilic factor A
Factor X (inactive) → Factor X (active)

Ca2+ ions and blood platelets

Factor II (inactive) → Factor II (active)
Vitamin K precursor Prothrombin Thrombin

Factor I (inactive) → Factor I (active)

© 2016 Paul Billiet ODWS Fibrinogen Fibrin
 The antihemophilic factors

 The blood clotting reaction is an enzyme

cascade involving Factors XII, XI, IX, X and II
 Each of these enzymes are proteases that cut
the next protein in line
 Other factors including proteins like Factor VIII
are essential as coenzymes.

© 2016 Paul Billiet ODWS

 Hemophilia

 About 85% of hemophiliacs suffer from classic

hemophilia (1 male in 10 000)
 They cannot produce factor VIII
 The rest show Christmas disease where they
cannot make factor IX
 The genes for both forms of hemophilia are sex
linked
 Hemophiliacs do clot their blood slowly because
there is an alternative pathway via
thromboplastin.
© 2016 Paul Billiet ODWS
 EXAMPLE PROBLEM:

● Hemophilia is a hereditary disease in which the

blood clotting process if defective. Classic
hemophilia results from an abnormal or missing
clotting factor VIII; it is inherited as an X-linked
recessive disorder (h).

● If a man without hemophilia and a woman who

is a carrier of the hemophilia allele have
children, what is the probability that…

X Y
H x X H X h
 what is the probability that:

a) they will have a daughter with hemophilia?

b) they will have a son with hemophilia?

c) their first son will have hemophilia?

d) their first daughter will be a carrier?

 European Royals &
Hemophilia

Royal family pedigree

© 2016 Paul Billiet ODWS
Queen Victoria’s Legacy in
Royal Families of Europe
 Alterations of chromosome
number or structure cause some
genetic disorders

● Large-scale chromosomal alterations often

lead to spontaneous abortions (miscarriages)
or cause a variety of developmental disorders
 Abnormal Chromosome
Number
● In NONDISJUNCTION, pairs of
homologous chromosomes do not
separate normally during meiosis
● As a result, one gamete receives two of
the same type of chromosome, and
another gamete receives no copy
 Meiosis I

Nondisjunction

Meiosis II

Nondisjunction

Gametes

n+1 n+1 n–1 n–1 n+1 n–1 n n

Number of chromosomes

Nondisjunction of homologous Nondisjunction of sister

chromosomes in meiosis I chromatids in meiosis I
● Aneuploidy results from the fertilization of
gametes in which nondisjunction occurred
● Offspring with this condition have an
abnormal number of a particular
chromosome
● a TRISOMIC zygote has three copies of
a particular chromosome
● a MONOSOMIC zygote has only one
copy of a particular chromosome
● Polyploidy is a condition
in which an organism has
more than two complete
sets of chromosomes
 Alterations of Chromosome
Structure
● Breakage of a chromosome can lead to four
types of changes in chromosome structure:
-Deletion removes a chromosomal segment
-Duplication repeats a segment
-Inversion reverses a segment within a
chromosome
-Translocation moves a segment from one
chromosome to another
 Deletion
A deletion removes a chromosomal
segment.

Duplication
A duplication repeats a segment.

An inversion reverses a segment Inversion

within a chromosome.

A translocation moves a segment

from one chromosome to another,
Reciprocal
nonhomologous one.
translocation
 Human Disorders Due to
Chromosomal Alterations
● Alterations of chromosome number and structure
are associated with some serious disorders
● Some types of aneuploidy appear to upset the
genetic balance less than others, resulting in
individuals surviving to birth and beyond
● These surviving individuals have a set of
symptoms, or syndrome, characteristic of the type
of aneuploidy
 Down Syndrome:

● Down Syndrome is an aneuploid condition

that results from three copies of
chromosome 21
● It affects about one out of every 700
children born in the United States
● The frequency of Down Syndrome increases
with the age of the mother
Aneuploidy of Sex Chromosomes

● Nondisjunction of sex chromosomes produces

a variety of aneuploid conditions
● Klinefelter syndrome is the result of an extra
chromosome in a male, producing XXY
individuals
● Monosomy X, called Turner syndrome,
produces X0 females, who are sterile; it is the
only known viable monosomy in humans
Disorders Caused by Structurally
Altered Chromosomes:
● One syndrome, cri du chat (“cry of the cat”),
results from a specific deletion in chromosome
5
● A child born with this syndrome is mentally
retarded and has a catlike cry; individuals
usually die in infancy or early childhood
● Certain cancers, including chronic
myelogenous leukemia (CML), are caused by
translocations of chromosomes
Normal chromosome 9 Reciprocal Translocated chromosome 9
translocation

Philadelphia
chromosome

Normal chromosome 22 Translocated chromosome 22