1. Autosomal recessive 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 recessive pedigree pattern to the segregation of genes at meiosis?

3. Homozygotes with two copies of the altered gene are affected Question: How can one relate an autosomal recessive pedigree pattern to the segregation of genes at meiosis? Reminder: Answer: 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

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

5. Parents AUTOSOMAL RECESSIVE INHERITANCE A parent who is a carrier of an autosomal recessive disorder has one copy of a normal gene and one copy of an altered gene of the particular pair

6. Parents Gametes AUTOSOMAL RECESSIVE INHERITANCE A carrier parent passes on either the normal gene or the altered gene into the eggs or sperm The other carrier parent passes on either the normal gene or the altered gene into his/her eggs or sperm

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

8. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE This child has inherited two copies of the normal gene - one from each parent

9. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE This child has inherited the normal gene from one parent but the altered gene from the other parent

10. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE

11. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE This child has inherited the altered gene from the first parent and the normal gene from the second parent

12. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE

13. Parents Gametes Offspring AUTOSOMAL RECESSIVE INHERITANCE This child has inherited the altered gene from each parent

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

15. Parents Gametes AUTOSOMAL RECESSIVE INHERITANCE AffectedUnaffected

16. AUTOSOMAL RECESSIVE INHERITANCE At conception, Each child of two parents who are carriers for the same autosomal recessive disorder therefore has a 1/4 (25%) chance of neither being affected nor a carrier of the disease 1/2 (50%) chance of being a carrier but unaffected 1/4 (25%) chance of inheriting the disease

17. But … what is the risk to a healthy sib of being a carrier for the recessive disease?

18. Once a child has been born and we know he or she is not affected by the disease (ie not a disease homozygote) this removes one of the four possibilities.

19. Once a child has been born and we know he or she is not affected by the disease (ie not a disease homozygote) this removes one of the four possibilities leaving three genotype possibilities for a healthy sib.

20. The three genotype possibilities for a healthy sib are: A normal homozygote A healthy carrier (heterozygote)

21. A healthy sib of a person with an autosomal recessive disorder therefore has a 2/3 chance of being a carrier.

22. Examples of Autosomal Recessive disorders Cystic fibrosis0.5 Recessive mental retardation0.5 Congenital deafness0.2 Phenylketonuria (PKU)0.1 Spinal muscular atrophy0.1 Recessive blindness0.1 Overall freq of recessive disease ~ 2/1000 Disease Freq/1000 births

23. 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 disorders.

24. 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