1. Autosomal dominant inheritance Risks to children where both parents are 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

2. Question:
What are the risks to children if both parents are affected by the same autosomal dominant condition?

3. Question:
What are the risks to children if both parents are affected by the same autosomal dominant condition?
Answer: By determining the different combinations of the genes of the parents which can be passed on to children as shown on the next few screens
Chromosome
Gene
Reminder:
Heterozygotes with one copy of the altered gene are affected

4. AUTOSOMAL DOMINANT: Both parents affected
Parents have two copies of autosomal genes: one copy on each of a particular pair of chromosomes

5. AUTOSOMAL DOMINANT: Both parents affected
It is very rare that the other parent has the same autosomal dominant disease - (but can occur - for example with achondroplasia or hypercholesterolaemia)
A parent with an autosomal dominant disorder has one copy of an altered gene and one normal gene of the particular pair

6. AUTOSOMAL DOMINANT: Both parents affected
Gametes
This affected parent passes on either the altered or the normal gene into the eggs or sperm
The affected parent passes on either the altered gene
or the normal gene into the eggs or sperm

7. AUTOSOMAL DOMINANT: Both parents affected
Gametes
There are
four different combinations
of the two genes from each parent

8. AUTOSOMAL DOMINANT: Both parents affected
Gametes
Offspring
This child has inherited the altered gene from the first affected parent and the altered gene from the other affected parent

9. AUTOSOMAL DOMINANT: Both parents affected
Gametes
Offspring
This child has inherited the altered gene from the affected parent but the normal gene from the other affected parent

10. AUTOSOMAL DOMINANT: Both parents affected
Gametes
Offspring

11. AUTOSOMAL DOMINANT: Both parents affected
Gametes
Offspring
This child has inherited the normal gene from the first parent and the altered gene from the second affected parent

12. AUTOSOMAL DOMINANT: Both parents affected
Gametes
Offspring

13. AUTOSOMAL DOMINANT: Both parents affected
Gametes
Offspring
This child has inherited the normal gene from the first affected parent and the normal gene from the second affected parent

14. Which children are affected by the disease?
AUTOSOMAL DOMINANT: Both parents affected
Parents
Gametes
Which children are affected by the disease?
Offspring

15. AUTOSOMAL DOMINANT: Both parents affected
Gametes
Affected
Affected
Affected
Unaffected

16. AUTOSOMAL DOMINANT: Both parents affected
Each child of a couple who both have an autosomal dominant disorder therefore has a
1/4 chance of being homozygous for the disease gene
1/2 chance of being a heterozygote for the disease
1/4 chance of being homozygous normal

17. The clinical effects of homozygosity for an autosomal dominant disorder
Most autosomal dominant disorders occur only in the heterozygous state because the disorder is relatively rare in the population.
For some conditions, being homozygous for the dominant disorder causes the individual to be more severely affected (as in achondroplasia) or for the disorder to have an earlier age of onset (eg familial hypercholesterolaemia).
In other disorders, for instance Huntington disease, homozygotes appear to have an indistinguishable clinical course from patients who are heterozygous for the mutant gene.
The difference may depend on how the nature of the mutation affects the gene product. For instance, conditions where the heterozygote has clinical features intermediate between homozygous normal and homozygous affected seem to be associated with alleles which stop a gene product from being produced. The heterozygotes are postulated to have half the normal concentration of the gene product whilst homozygous affected individuals make none.

18. Occasionally, each parent can be affected by a different dominant disorder.
What are the risks to their children?

19. AUTOSOMAL DOMINANT: both parents affected; genes at different loci
Gametes
Affected by both disorders
Affected by first disorder
Affected by second disorder
Unaffected

20. Autosomal dominant conditions are part of the group of single gene disorders, which also include autosomal recessive, and X-linked conditions.
Chromosome
Gene
They are important clinically because of the high risks to other family members.

21. The end! Thank you for completing this revision aid
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© P Farndon 2003