x-linked recessive inheritance where the father is affected: the basics a tutorial to show how the...
DESCRIPTION
Hemizygotes (males) with one copy of the altered gene are affected Question: How can one understand the risks of an X- linked recessive condition where a father is affected? Reminder: Answer: By imagining which of the sex chromosomes of the parents have been passed on to children as shown on the next few screens X-Chromosome GeneTRANSCRIPT
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 X-linked recessive condition where a father is affected?
I:1 I:2
II:2II:1 II:3
III:2 III:3 III:4III:1
IV:1 IV:2
Hemizygotes (males) with one copy of the altered gene are affected
Question:How can one understand the risks of an X-linked recessive condition where a father is affected?
Reminder:
Answer:By imagining which of the sex chromosomes of the parents have been passed on to children as shown on the next few screens
X-Chromosome
Gene
Humans have 23 pairs of chromosomes:22 pairs of autosomes and 1 pair of sex chromosomes
Male karyotype
Female karyotype
The male sex chromosomes: an X and a Y
The female sex chromosomes: two X chromosomes
Parents
X-LINKED RECESSIVE INHERITANCE: father affected
Father MotherAffected
An affected male will have an X chromosome with a altered gene and a Y chromosome
A woman who is not a carrier of an X-linked recessive disorder has two copies of the normal gene - one on each X chromosome
Parents
Gametes
Father Mother
X Y XX
Affected
The father passes on either his X chromosome containing the altered gene
or his Y chromosome (and so determines the sex of the fetus)
The mother passes on one
or the other of her X chromosomes (both with normal genes)
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Father Mother
X Y XX
Affected
There are four different combinations
of the two chromosomes from each parent
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Offspring
Father Mother
X Y XX
Daughter
Affected
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
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Offspring
Father Mother
X Y XX
Daughter Daughter
Affected
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
Gametes
Offspring
Father Mother
X Y XX
Daughter Daughter Son
Affected
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Offspring
Father Mother
X Y XX
Affected
This child has inherited the paternal Y chromosome (and so is male) and a maternal X chromosome with a normal gene
Son
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Offspring
Father Mother
X Y XX
Daughter Daughter Son Son
Affected
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Offspring
Father Mother
X Y XX
Son
Affected
This child has inherited the paternal Y chromosome (and so is male) and the other maternal X chromosome with a normal gene
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Offspring
Father Mother
X Y XX
Daughter Daughter Son Son
Affected
Which children are affected by the disease?
X-LINKED RECESSIVE INHERITANCE: father affected
Parents
Gametes
Father Mother
X Y XX
Daughter Daughter Son Son
Unaffected carrier
Unaffected male
Affected
Unaffected carrier
Unaffected male
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 X-
chromosome with the altered gene.
X-LINKED RECESSIVE INHERITANCE: father affected
Examples of X-linked recessive diseases
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
UK frequency / 10,000 males
They are important clinically because of
the high risks to other family members.
X-linked recessive conditions are part of the
group of single gene disorders, which also
include autosomal dominant and recessive disorders.
X-Chromosome
Gene
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