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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

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Page 1: 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

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

Page 2: 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

Question:What are the risks to the children of someone with an autosomal recessive disorder?

Page 3: 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

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

Page 4: 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

Parents

AUTOSOMAL RECESSIVE: one parent affected

Parents have two copies of autosomal genes:one copy on each of a particular pair of chromosomes

Page 5: 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

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

Page 6: 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

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

Page 7: 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

Parents

Gametes

AUTOSOMAL RECESSIVE: one parent affected

There are

four different combinations

of the two genes from each parent

Affected

Page 8: 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

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

Page 9: 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

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

Page 10: 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

Parents

Gametes

Offspring

AUTOSOMAL RECESSIVE: one parent affected

Affected

Page 11: 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

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

Page 12: 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

Parents

Gametes

Offspring

AUTOSOMAL RECESSIVE: one parent affected

Affected

Page 13: 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

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

Page 14: 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

Parents

Gametes

Offspring

AUTOSOMAL RECESSIVE: one parent affected

Which children are affected by the disease?

Affected

Page 15: 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

Parents

Gametes

AUTOSOMAL RECESSIVE: one parent affected

Unaffectedcarrier

Unaffected carrier

Unaffected carrier

Unaffectedcarrier

Affected

Page 16: 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

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.

Page 17: 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

• 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”.

Page 18: 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

Parents

Gametes

AUTOSOMAL RECESSIVE: one parent affected, other parent a carrier

AffectedAffected Unaffected carrier

Unaffected carrier

Affected

Page 19: 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

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?

Page 20: 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

Occasionally, each parent can be affected by the same autosomal recessive disorder.

What are the risks to their children?

Affected Affected

Page 21: 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

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

Page 22: 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

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.

Page 23: 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

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

Page 24: 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

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

Page 25: 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

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


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