Download where the father is affected

X-linked recessive inheritance
where the father is affected:
the basics
a tutorial to show how the genes
segregate to give the typical
pedigree pattern
Professor P Farndon,
Clinical Genetics Unit, Birmingham
Women’s Hospital
13.11.06
Question:
How can one understand the risks of an Xlinked recessive condition where a father is
affected?
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II:1
III:1
IV:1
III:2
IV:2
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II:2
III:3
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Question:
How can one understand the risks of an Xlinked recessive condition where a father is
affected?
Answer:
By imagining which of the sex
chromosomes of the parents have been
passed on to children as shown on the
next few screens
Gene
Reminder:
Hemizygotes (males) with one copy of
the altered gene are affected
X-Chromosome
Male karyotype
Female karyotype
Humans have 23 pairs of
chromosomes:
22 pairs of autosomes
and
1 pair of sex
chromosomes
The male sex
chromosomes: an X
and a Y
The female sex
chromosomes: two X
chromosomes
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
An affected male will
have an X chromosome
with a altered gene and a
Y chromosome
Mother
A woman who is not
a carrier of an Xlinked recessive
disorder has two
copies of the normal
gene - one on each
X chromosome
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
The father
passes on
either his X
chromosome
containing
the altered
gene
Y
or his Y
chromosome
(and so
determines
the sex of the
fetus)
X
The
mother
passes on
one
X
or the other of
her X
chromosomes
(both with
normal genes)
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Y
X
There are
four different combinations
of the two chromosomes from each
parent
X
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Y
X
Offspring
This child has inherited the paternal X
chromosome with the altered gene (and
so is female) and the maternal X
chromosome with the normal gene
Daughter
X
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Y
X
X
Offspring
Daughter
Daughter
This child has inherited the
paternal X chromosome with
the altered gene (and so is
female) and the other
maternal X chromosome with
a normal gene
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Y
X
Offspring
Daughter
Daughter
Son
X
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Y
X
Offspring
This child has inherited the paternal
Y chromosome (and so is male) and
a maternal X chromosome with a
normal gene
Son
X
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Y
X
X
Offspring
Daughter
Daughter
Son
Son
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Y
X
X
Offspring
This child has inherited the paternal Y
chromosome (and so is male) and the
other maternal X chromosome with a
normal gene
Son
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Offspring
Daughter
Y
X
X
Which children are affected by the disease?
Daughter
Son
Son
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Affected
Father
Mother
Gametes
X
Unaffected
carrier
Daughter
Y
Unaffected
carrier
Daughter
X
X
Unaffected
male
Unaffected
male
Son
Son
X-LINKED RECESSIVE INHERITANCE: father affected
All the children of a male with an X-linked recessive
disorder are therefore unaffected by his X-linked disease.
All his daughters will be carriers. Their sons will inherit
either the X-chromosome with the normal gene or the Xchromosome with the altered gene.
Examples of X-linked recessive diseases
UK frequency / 10,000 males
Fragile X syndrome
5
Non-specific X-linked mental retardation
5
Duchenne muscular dystrophy
3
Becker muscular dystrophy
0.5
Haemophilia A (factor VIII)
2
Haemophilia B (factor IX)
0.3
X-linked recessive
conditions are part of the
group of single gene
disorders, which also
include autosomal dominant
and recessive disorders.
They are important
clinically because of
the high risks to other
family members.
Gene
X-Chromosome
The end!
• Thank you for completing this revision aid
• We are interested in your comments about this
aid. Please email Professor Farndon.
([email protected])
© P Farndon 2003