1. Autosomal dominant inheritance: 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 18.02.03

2. Question: How can one relate an autosomal dominant pedigree pattern to the segregation of genes at meiosis?

3. Heterozygotes with one copy of the abnormal gene are affected Question: How can one relate an autosomal dominant pedigree pattern to the segregation of genes at meiosis? Reminder: Answer: By imagining which of the two genes of the parent with the condition have been passed on to children as shown on the next few screens Chromosome Gene

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

5. Parents AUTOSOMAL DOMINANT INHERITANCE A parent with an autosomal dominant disorder has one copy of an altered gene and one normal gene of the particular pair

6. Parents Gametes AUTOSOMAL DOMINANT INHERITANCE The affected parent passes on either the altered gene or the normal gene into the eggs or sperm The unaffected parent passes on one or other of his/her normal genes into the eggs or sperm

7. Parents Gametes AUTOSOMAL DOMINANT INHERITANCE There are four different combinations of the two genes from each parent

8. Parents Gametes Offspring AUTOSOMAL DOMINANT INHERITANCE This child has inherited the altered gene from the affected parent and one of the normal genes from the unaffected parent

9. Parents Gametes Offspring AUTOSOMAL DOMINANT INHERITANCE This child has inherited the altered gene from the affected parent but the other normal gene from the unaffected parent

10. Parents Gametes Offspring AUTOSOMAL DOMINANT INHERITANCE

11. Parents Gametes Offspring AUTOSOMAL DOMINANT INHERITANCE This child has inherited the normal gene from the affected parent and one of the normal genes from the unaffected parent

12. Parents Gametes Offspring AUTOSOMAL DOMINANT INHERITANCE

13. Parents Gametes Offspring AUTOSOMAL DOMINANT INHERITANCE This child has inherited the normal gene from the affected parent and the other normal gene from the unaffected parent

14. Parents Gametes Offspring AUTOSOMAL DOMINANT INHERITANCE Which children are affected by the disease?

15. Parents Gametes AUTOSOMAL DOMINANT INHERITANCE Affected Unaffected

16. AUTOSOMAL DOMINANT INHERITANCE AffectedUnaffected Each child of someone with an autosomal dominant disorder therefore has a 1/2 50% 50:50 chance of inheriting the gene alteration

17. Autosomal dominant disorders DiseaseFrequency/10,000 births Dominant otosclerosis30 Familial hypercholesterolaemia20 von Willebrand disease10 Adult polycystic kidney disease10 Huntington disease 5 Neurofibromatosis 4 Myotonic dystrophy 2 Tuberous sclerosis 1 Familial adenomatous polyposis 1 Dominant blindness 1 Total (of all dominant disorders)100

18. I:1 AA I:2 AB II:1 AA II:2 AB II:3 BB ? III:1 BB Tom They are important clinically because of the high risks to other family members. Autosomal dominant conditions are part of the group of single gene disorders, which also include autosomal recessive and X-linked disorders.

19. 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