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X-linked recessive inheritance where the mother is a carrier:
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 relate an X-linked recessive pedigree pattern to the segregation of genes at meiosis?
I:1John Hodgkin
I:2Celia
II:2Kathleen
II:1Peter Smith
II:3Gerald
III:2Jean
III:3Paul Smith
III:4Kevin Smith
III:1Andrew Cox
IV:1Jason
IV:2Duane
Hemizygotes (males) with one copy of the altered gene are affected
Question:How can one relate an X-linked recessive pedigree pattern to the segregation of genes at meiosis?
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
Parents
X-LINKED INHERITANCE: mother a carrier
Father Mother
CarrierUnaffected
An unaffected male will have an X chromosome with a normal gene and a Y chromosome
A woman who is a carrier of an X-linked recessive disorder has one copy of a normal gene
and one copy of an altered gene of the particular pair
Parents
Gametes
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
CarrierUnaffected
The father passes on either his X chromosome
or his Y chromosome (and so determines the sex of the fetus)
The mother passes on either the X chromosome containing the normal allele
or the X chromosome containing the altered allele
Parents
Gametes
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
CarrierUnaffected
There are
four different combinations
of the two chromosomes from each parent
Parents
Gametes
Offspring
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
Daughter
CarrierUnaffected
This child has inherited the paternal X chromosome (and so is female) and the maternal X chromosome with the normal gene
Parents
Gametes
Offspring
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
Daughter Daughter
CarrierUnaffected
This child has inherited the paternal X chromosome (and so is female) and the maternal X chromosome with the altered gene
Parents
Gametes
Offspring
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
Daughter Daughter Son
CarrierUnaffected
Parents
Gametes
Offspring
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
CarrierUnaffected
This child has inherited the paternal Y chromosome (and so is male) and the maternal X chromosome with the normal gene Son
Parents
Gametes
Offspring
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
Daughter Daughter Son Son
CarrierUnaffected
Parents
Gametes
Offspring
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
Son
CarrierUnaffected
This child has inherited the paternal Y chromosome (and so is male) and the maternal X chromosome with the altered gene
Parents
Gametes
Offspring
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
Daughter Daughter Son Son
CarrierUnaffected
Which children are affected by the disease?
Parents
Gametes
X-LINKED INHERITANCE: mother a carrier
Father Mother
X Y XX
Daughter Daughter Son Son
Unaffected carrier
Affected male
CarrierUnaffected
Unaffected female
Unaffected male
X-LINKED INHERITANCE: mother a carrier
One has to be very careful in explaining these risks to couples where the woman is a carrier for an X-linked
disorder to avoid potential confusion.
If the sex of the fetus is unknown, there is a 1 in 4 chance (25%) that he will be both male and affected.
X-LINKED INHERITANCE: mother a carrier
Parents will often wish to have prenatal diagnosis by fetal sexing for serious X-linked recessive disorders, and so will want to know the sex of the fetus.
“If you have a girl, she has a 1 in 2 chance (50%) of being a carrier “(and usually completely asymptomatic).
“If you have a boy, he has a 1 in 2 chance (50%) of being affected.”
However, we usually explain the risks like this:
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 2001