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BMS2042 Lecture 2
Sex-linked Inheritance
Associate Professor Francine Marques

References: @FZMarques
Klug 12th ed, Chapter 4
Strachan & Read 4th ed, Chapter 3
What we will learn today:
• Reciprocal crosses on X-chromosome
• X-linked patterns of single-gene inheritance
• Y-linked inheritance
• How to calculate basic probability for genetic counselling
Problem
identification Intercultural
& solution competence
Structure of the X and Y
chromosomes
X chromosome
• 851 genes and 664 non-coding
genes
Y chromosome
• Contains 66 coding genes and 107
non-coding genes
• Most genes have a role in sex
development
Week 9
X and Y info from Ensembl GRCh38.p1
Sex-linked Inheritance
Discovered by Thomas Hunt
Morgan, found white-eyed
mutant of Drosophila.
Found different results from reciprocal crosses, where

phenotypes of male and female parents reversed.
He was awarded Nobel Prize in Physiology or
Medicine in 1933
Reciprocal crosses
white eyed male x red eyed female

X
Hypothesised that
white gene was on X
F1 - all red
chromosome,
females had two
copies and males
red eyed male x white eyed female only one (called
hemizygous).
X
F1 - all males white, all females red

Reciprocal crosses Diagramming the crosses
w+ for wild type (red) w for white
white eyed male x red eyed female
w w+ w+
X
X Y X X X
F1 - all red w+ w+ w
X Y X X
red eyed male x white eyed female

w+ w w
X X Y X X X
F1 - all males white, all females red w w+ w

X Y X X
X-linked inheritance
X X XX X X XX
X X XX XX XX
X-linked recessive inheritance
• It affects mainly males.
• Affected males are usually born to unaffected parents.
• The mother is normally an asymptomatic carrier and may

have affected male relatives.
• Females may be affected if the father is affected and the

mother is a carrier, or occasionally as a result of non-random
X-inactivation.
• There is no male-to-male transmission in the pedigree.

• Females have 3 possible genotypes:
XAXA, XAXa, XaXa
• Males have 2 possible genotypes:

XAY, XaY  hemizygous
Colour blindness (daltonism)
In Australia, about 8% of males and 0.4% of females are

colour blind
Hemophilia A and B
(variants in the genes for F8 or F9)
• Disorders of coagulation: blood fails to clot normally
because of a deficiency of factor VIII or IX
• Hemophilia A: 1 in 5,000–10,000 newborn males

• Hemophilia B: 1 in 100,000 newborn males
X-linked dominant inheritance
• It affects either sex, but often excess of females.
• Usually at least one parent is affected.
• Females are often more mildly and more variably

affected than males (due to X inactivation).
• The child of an affected female, regardless of its sex,

has a 50% chance of being affected.
• Affected males can transmit to daughters but not sons

(no male to male transmission).
• Usually they are rare diseases and may be caused by

new mutations or germ-line mutations.
Affected: XAY, XAXa Healthy: XaY, XaXa
Affected: XAY, XAXa Healthy: XaY, XaXa
X-linked dominant inheritance
Griffiths 9 Fig 2.39

X chromosome inactivation
• One X chromosome in each cell
is randomly inactivated early in
the embryonic development of Week 9
females  mosaics
• This ensures that females, who

have two copies of the X
chromosome, will produce X-
linked gene products in quantities
roughly similar to those produced
in males: dosage compensation
Q: If a woman carries a recessive variant

in a gene in the X chromosome, could
she present symptoms?
Genes in the Y chromosome
SRY
Refusal to ask for directions when lost (ANTI-STOP)
Inability to See/Hear Obvious (ISHO)
Channel Flipping (FLIP)
Ability to recite movie scripts ad nauseum (MOVIE)
Ability to tell and remember jokes (JOKE)
Beer Consumption Controlling factor (BCCF)
Air Guitar (AIR)
Addiction to Death & Destruction Movies (Terminator)
Inability to express affection on phone (ME TOO)
Y-linked inheritance – Hairy earlobes
Controversial and
unlikely Y-linked
Griffiths 9 Fig 2.40

https://www.omim.org/entry/425500?search=Y-linked&highlight=%22%28ylinked%7C%22y%7Clinked%22%29%22%20ylinked%20%22y%20linked%22
https://jmg.bmj.com/content/41/6/e80.long
1 in 2,000 to 1 in 3,000 males of all ethnic groups
MO, moderate oligozoospermia;

SO, severe oligozoospermia.
https://jmg.bmj.com/content/42/3/209
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314981/
Using Mendel’s Laws to predict progeny of
crosses - Rules of probability
Product rule: The probability of independent events occurring

together is the product of the probabilities of the individual
events.
eg. prob. of event 1 and event 2
= prob. event 1 x prob. event 2
Sum rule: The probability of either of two mutually exclusive

events occurring is the sum of their individual probabilities.
eg. prob. of event 1 or event 2
= prob event 1 + prob event 2
Week 6
Using Mendel’s Laws in Genetic Counselling
Example Problem – Cystic fibrosis is an autosomal
recessive disorder. Two heterozygous parents are
expecting a baby.
1. What is the probability that the baby is affected?
Cc x Cc C c
C CC Cc
c Cc cc
Do a Punnett sq, expect ¼ to be affected on average

expecting a baby.

2. What is the probability that the baby is a
homozygote?
Two types of homozygotes,
homozygous of mutant and
normal….so ¼ + ¼
expecting a baby.
2. What is the probability that the baby is a
homozygote?
3. What is the probability that this baby is affected,
and they then have a second baby who is
unaffected?
Affected is ¼, unaffected is ¾
so probability is ¼ x ¾ = 3/16
Example problem:
Duchenne muscular dystrophy is an X linked
recessive disorder.
1. If a woman who is a carrier of a DMD variant has
a normal partner, what is the probability of
having an affected child?
XD wild type allele Xd carrying the mutation
XD Xd x XD Y
XD XD XD Xd XD Y Xd Y
affected son so probability is ¼
Example problem:
recessive disorder.
1. If a woman who is a carrier of a DMD variant has
a normal partner, what is the probability of
having an affected child?
2. In the same situation as (1), if they have two
children what is the probability of both being
affected?
probability of one affected child is ¼

probability of two affected children is ¼ x ¼
Example problem:
recessive disorder.
3. What is the probability that a different woman
whose mother’s brother had the disease will
have received the disease allele?
XDXd XDY
XDY
XDXD ½ XdY
XDXd ½
XDXD ½ Probability is ½ x ½ = ¼
XDXd ½
Example of question
• What is the most
likely pattern of
inheritance?
Why?
• What is the
genotype of III3?
• Who are carriers
of a variant?
X-linked recessive
III3: XaY
Carriers: I2, II2, II5
Example of question
• What is the
most likely
pattern of
inheritance?
Why?
• What is the
genotype of
III6?
Autosomal dominant
III6: Aa
Example of question
• What is the most
likely pattern of
inheritance?
Why?
• What is the
chance that
IV10 would have
X-linked dominant
an affected son
IV10 genotype: XAXa if married to a
XA Xa healthy man?
Xa XAXa XaXa
Y XAY XaY
50% of all sons
Learning outcomes
• Know that X linked inheritance was
discovered by Morgan using reciprocal
crosses and white-eyed mutant of Drosophila
• Recognise autosomal versus X-linked versus
Y-linked patterns of single-gene inheritance
and determine genotypes
• Use Mendel’s Laws to predict progeny and
calculate probability
If you are thinking…
“I have questions” or
“I would love to talk to you”
Post Questions: please post them on Moodle
Chat with Callum: book via Moodle, available on

Chat Fridays 10-11 am
Drop-in Drop-in session: Friday 1-2 pm

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BMS2042 Lecture 2

Associate Professor Francine Marques

Found different results from reciprocal crosses, where

white eyed male x red eyed female

F1 - all males white, all females red

red eyed male x white eyed female

F1 - all males white, all females red w w+ w

• Affected males are usually born to unaffected parents.

• The mother is normally an asymptomatic carrier and may

• Females may be affected if the father is affected and the

• There is no male-to-male transmission in the pedigree.

• Males have 2 possible genotypes:

In Australia, about 8% of males and 0.4% of females are

• Hemophilia A: 1 in 5,000–10,000 newborn males

• Usually at least one parent is affected.

• Females are often more mildly and more variably

• The child of an affected female, regardless of its sex,

• Affected males can transmit to daughters but not sons

• Usually they are rare diseases and may be caused by

Griffiths 9 Fig 2.39

• This ensures that females, who

Q: If a woman carries a recessive variant

Griffiths 9 Fig 2.40

MO, moderate oligozoospermia;

Product rule: The probability of independent events occurring

Sum rule: The probability of either of two mutually exclusive

1. What is the probability that the baby is affected?

Do a Punnett sq, expect ¼ to be affected on average

1. What is the probability that the baby is affected?

XD wild type allele Xd carrying the mutation

probability of one affected child is ¼

Post Questions: please post them on Moodle

Chat with Callum: book via Moodle, available on

Drop-in Drop-in session: Friday 1-2 pm

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