Transcript Autosomal recessive inheritance

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
II:1
Julia
II:2
Edward
II:3
Zoe
II:4
Elizabeth
I:2
Mary
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
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Parents have two copies of autosomal genes:
one copy on each of a particular pair of
chromosomes
AUTOSOMAL RECESSIVE INHERITANCE
Parents
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
AUTOSOMAL RECESSIVE INHERITANCE
Parents
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
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
There are
four different combinations
of the two genes from each parent
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
This child has inherited two copies
of the normal gene - one from each
parent
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
This child has inherited the
normal gene from one parent
but the altered gene from the
other parent
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
This child has inherited the
altered gene from the first
parent and the normal
gene from the second
parent
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
This child has inherited
the altered gene from
each parent
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
Which children are affected by the disease?
AUTOSOMAL RECESSIVE INHERITANCE
Parents
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
II:1
John
Hobson
But …
what is the risk to a healthy sib of
being a carrier for the recessive
disease?
III:1
Mervin
Hobson
II:2
Christine
Hobson
III:2
Alice
Hobson
III:3
Richard
Hobson
I:2
II:3
Christopher
Whitehead
II:4
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
Disease
Freq/1000 births
Cystic fibrosis
0.5
Recessive mental retardation
0.5
Congenital deafness
0.2
Phenylketonuria (PKU)
0.1
Spinal muscular atrophy
0.1
Recessive blindness
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.
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