Transcript Autosomal dominant inheritance

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
Question:
How can one relate an autosomal dominant
pedigree pattern to the segregation of genes
at meiosis?
I:1
John Jones
II:1
Sophia
III:1
Roger
IV:1
Stephanie
II:2
David
III:2
Marion
IV:2
Thomas
III:3
James Fox
IV:3
Vanessa
IV:4
John
I:2
Mary
II:3
Elizabeth
III:4
Joanna
IV:5
Clive
II:4
Brenda
III:5
Ken Marriott
IV:6
Anna
III:6
Margaret
IV:7
Robert
IV:8
Suzanne
III:7
III:8
Christopher Anthony Miles
IV:9
Katy
IV:10
Sam
III:9
Gill
IV:11
Matt
Question:
How can one relate an autosomal dominant
pedigree pattern to the segregation of genes
at meiosis?
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
Gene
Reminder:
Heterozygotes with one copy of the
abnormal gene are affected
Chromosome
AUTOSOMAL DOMINANT INHERITANCE
Parents
Parents have two copies of autosomal genes:
one copy on each of a particular pair of
chromosomes
AUTOSOMAL DOMINANT INHERITANCE
Parents
A parent with an
autosomal dominant
disorder has one copy of
an altered gene and one
normal gene of the
particular pair
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
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
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
There are
four different combinations
of the two genes from each parent
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Offspring
This child has inherited the altered
gene from the affected parent and
one of the normal genes from the
unaffected parent
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Offspring
This child has inherited the
altered gene from the affected
parent but the other normal
gene from the unaffected
parent
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Offspring
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Offspring
This child has inherited the
normal gene from the
affected parent and one of
the normal genes from the
unaffected parent
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Offspring
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Offspring
This child has inherited
the normal gene from the
affected parent and the
other normal gene from
the unaffected parent
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Offspring
Which children are affected by the disease?
AUTOSOMAL DOMINANT INHERITANCE
Parents
Gametes
Affected
Affected
Unaffected
Unaffected
AUTOSOMAL DOMINANT INHERITANCE
Each child of someone with
an autosomal dominant
disorder therefore has a
1/2
50%
Affected
Unaffected
50:50
chance of inheriting the
gene alteration
Autosomal dominant disorders
Disease
Dominant otosclerosis
Familial hypercholesterolaemia
von Willebrand disease
Adult polycystic kidney disease
Huntington disease
Neurofibromatosis
Myotonic dystrophy
Tuberous sclerosis
Familial adenomatous polyposis
Dominant blindness
Total (of all dominant disorders)
Frequency/10,000 births
30
20
10
10
5
4
2
1
1
1
100
Autosomal dominant
conditions are part of the
group of single gene
disorders, which also
include autosomal recessive
and X-linked disorders.
They are important
clinically because of
the high risks to other
family members.
I:1
AA
II:1
AA
I:2
AB
II:2
AB
II:3
BB
?
III:1
BB
Tom
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