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

Question:
How can one relate an autosomal recessive pedigree pattern to the segregation of genes at meiosis?
I:1
Patrick McKee
I:2
Mary
II:1
Julia
II:2
Edward
II:3
Zoe
II:4
Elizabeth
II:5
Charles
II:6
William
II:7
Lucy
II:8
Laura

Question:
How can one relate an autosomal recessive pedigree pattern to the segregation of genes at meiosis?
Answer:
By imagining which of the two genes of the parents have been passed on to children as shown on the next few screens
Gene Reminder:
Homozygotes with two copies of the altered gene are affected
Chromosome

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

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

Parents
AUTOSOMAL RECESSIVE INHERITANCE
Gametes
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

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

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

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

Parents
AUTOSOMAL RECESSIVE INHERITANCE
Gametes
Offspring

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

Parents
AUTOSOMAL RECESSIVE INHERITANCE
Gametes
Offspring

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

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

Parents
AUTOSOMAL RECESSIVE INHERITANCE
Gametes
Unaffected Unaffected Unaffected Affected

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

I:1 I:2
But … what is the risk to a healthy sib of being a carrier for the recessive disease?
II:1
John
Hobson
II:2
Christine
Hobson
II:3
Christopher
Whitehead
II:4
III:1
Mervin
Hobson
III:2
Alice
Hobson
III:3
Richard
Hobson

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.

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.

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

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

Examples of Autosomal Recessive disorders
Cystic fibrosis
Recessive mental retardation
Congenital deafness
Phenylketonuria (PKU)
Spinal muscular atrophy
Recessive blindness
0.5
0.5
0.2
0.1
0.1
0.1
Overall freq of recessive disease ~ 2/1000

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

!
• 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