Autosomal recessive inheritance
Risks to children where a parent 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:
What are the risks to the children of
someone with an autosomal recessive
disorder?
Question:
What are the risks to the children of
someone with an autosomal recessive
disorder?
Answer:
We can deduce these risks by
imagining which of the two genes of
the parents have been passed on to
children as shown on the next few
screens
Gene
Reminder:
Homozygotes with two copies of the
altered gene are affected
Chromosome
AUTOSOMAL RECESSIVE: one parent affected
Parents
Parents have two copies of autosomal genes:
one copy on each of a particular pair of
chromosomes
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
A parent who is affected
by an autosomal
recessive disorder has
two copies of the altered
gene
A partner from the
general population,
who is unrelated, is
unlikely to be a carrier
for the same disorder,
and so will have two
copies of the normal
gene
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
The affected
parent passes
on a copy of
the altered
gene
into all of
his/her
gametes
The other parent
passes on copies
of the normal
gene into his/her
eggs or sperm
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
There are
four different combinations
of the two genes from each parent
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Offspring
This child has inherited a copy of
the altered gene from the affected
parent and a copy of the normal
gene from the unaffected parent
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Offspring
This child has inherited the
altered gene from the affected
parent but the normal gene
from the other parent
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Offspring
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Offspring
This child has inherited the
altered gene from the
affected parent and the
normal gene from the
second parent
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Offspring
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Offspring
This child has inherited
the altered gene from the
affected parent and a
normal gene from the
unaffected parent
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Offspring
Which children are affected by the disease?
AUTOSOMAL RECESSIVE: one parent affected
Parents
Affected
Gametes
Unaffected
carrier
Unaffected
carrier
Unaffected
carrier
Unaffected
carrier
AUTOSOMAL RECESSIVE: one parent affected
None of the children of a person affected by an autosomal
recessive condition will therefore be affected, as long as the
partner is not a carrier for the same condition.
All the children will be carriers, but healthy.
Occasionally a person with an autosomal recessive disorder
has a child affected with the same disorder. This is
discussed on the following pages.
• When a person with an autosomal recessive condition
has a child with the same condition, their unaffected
partner must be a carrier for a mutation at the same
gene locus. This is rare if the partner is unrelated and
from the general population.
• Where a partner is a carrier for the same recessive
disorder, the risk to a child of having the condition is 1 in
2 as shown on the next slide.
•
When a parent and child are affected with the same autosomal recessive
condition, the pedigree can be described as showing “pseudo-dominant
inheritance”.
AUTOSOMAL RECESSIVE: one parent affected, other parent a carrier
Parents
Affected
Gametes
Unaffected
carrier
Affected
Unaffected
carrier
Affected
How do we calculate the probability that someone
from the general population is a carrier for the
same autosomal recessive disorder?
It may be possible by using the Hardy-Weinberg
equation
p2 + 2pq + q2 = 1
and knowledge of the frequency of affected
homozygotes (q2) in the particular population.
Having calculated the frequency of carriers, this can
then be used in genetic counselling to calculate the
risk of an affected person having a child affected
with the same condition.
Occasionally, each parent can be affected by
the same autosomal recessive disorder.
What are the risks to their children?
Affected
Affected
AUTOSOMAL RECESSIVE: both parents affected
Parents
Affected
If the disease in
both parents is
caused by the
same gene, all
their children will
be affected
Affected
Gametes
Affected
Affected
Affected
Affected
Occasionally, each parent can appear to be
affected by the same autosomal recessive
disorder, but all their children are unaffected.
What is the explanation?
Come from same small
village in Norfolk.
I:2
Celia
I:1
William Penfell
III:1
Beth
III:2
Tony
III:3
Vincent
III:4
June
III:5
Kirsty
III:6
Craig
II:6
Christine
Deaf from birth
No speech
Sign language
II:5
Richard
II:4
Fiona
II:3
Paul
II:2
Mark Penfell
Deaf from birth
No speech
Sign language
II:1
Margaret
Adopted.
Deaf, no speech.
Brother with deafness
Parents with normal hearing
III:7
Darren
III:8
Hope
II:7
Edward
II:8
May
AUTOSOMAL RECESSIVE: both parents affected; genes at different loci
Parents
Affected
Gametes
Unaffected
If the disease in
both parents is
caused by
different genes at
different loci, all
their children will
be unaffected
Unaffected
Unaffected
All are carriers for both disease genes
Affected
Unaffected
Autosomal recessive
conditions are part of the
group of single gene
disorders, which also
include autosomal
dominant, and X-linked
conditions.
They are important
clinically because of
the high risks to other
family members.
Gene
Chromosome
The end!
• Thank you for completing this revision aid
• We are interested in your comments about this
aid. Please email Professor Farndon.
(p.a.farndon@bham.ac.uk)
© P Farndon 2003