Autosomal recessive inheritance Risks to children where a parent is affected: the basics a tutorial...
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Transcript of Autosomal recessive inheritance Risks to children where a parent is affected: the basics a tutorial...
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
Homozygotes with two copies of the altered gene are affected
Question:What are the risks to the children of someone with an autosomal recessive disorder?
Reminder:
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
Chromosome
Gene
Parents
AUTOSOMAL RECESSIVE: one parent affected
Parents have two copies of autosomal genes:one copy on each of a particular pair of chromosomes
Parents
AUTOSOMAL RECESSIVE: one parent 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
Affected
Parents
Gametes
AUTOSOMAL RECESSIVE: one parent affected
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
Affected
Parents
Gametes
AUTOSOMAL RECESSIVE: one parent affected
There are
four different combinations
of the two genes from each parent
Affected
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE: one parent affected
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
Affected
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE: one parent affected
This child has inherited the altered gene from the affected parent but the normal gene from the other parent
Affected
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE: one parent affected
This child has inherited the altered gene from the
affected parent and the normal gene from the
second parent
Affected
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE: one parent affected
This child has inherited the altered gene from the
affected parent and a normal gene from the
unaffected parent
Affected
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE: one parent affected
Which children are affected by the disease?
Affected
Parents
Gametes
AUTOSOMAL RECESSIVE: one parent affected
Unaffectedcarrier
Unaffected carrier
Unaffected carrier
Unaffectedcarrier
Affected
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”.
Parents
Gametes
AUTOSOMAL RECESSIVE: one parent affected, other parent a carrier
AffectedAffected Unaffected carrier
Unaffected carrier
Affected
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.
How do we calculate the probability that someone from the general population is a carrier for the same autosomal recessive disorder?
Occasionally, each parent can be affected by the same autosomal recessive disorder.
What are the risks to their children?
Affected Affected
Parents
Gametes
AUTOSOMAL RECESSIVE: both parents affected
AffectedAffected Affected Affected
If the disease in both parents is caused by the same gene, all their children will be 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?
I:1William Penfell
II:2Mark Penfell
Deaf from birthNo speech
Sign language
II:3Paul
II:4Fiona
II:5Richard
II:6Christine
Deaf from birthNo speech
Sign language
II:7Edward
II:8May
II:1MargaretAdopted.
Deaf, no speech.Brother with deafness
Parents with normal hearing
III:1Beth
III:2Tony
III:3Vincent
III:4June
III:5Kirsty
III:6Craig
III:7Darren
III:8Hope
I:2Celia
Come from same smallvillage in Norfolk.
Parents
Gametes
AUTOSOMAL RECESSIVE: both parents affected; genes at different loci
UnaffectedUnaffected Unaffected Unaffected
All are carriers for both disease genes
If the disease in both parents is caused by different genes at different loci, all their children will be unaffected
Affected
Affected
They are important clinically because of
the high risks to other family members.
Autosomal recessive conditions are part of the
group of single gene disorders, which also
include autosomal dominant, and X-linked
conditions.
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