autosomal recessive inheritance: the basics a tutorial to show how the genes segregate to give the...
DESCRIPTION
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 GeneTRANSCRIPT
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:1Patrick McKee
I:2Mary
II:1Julia
II:2Edward
II:3Zoe
II:4Elizabeth
II:5Charles
II:6William
II:7Lucy
II:8Laura
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
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
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
Parents
Gametes
AUTOSOMAL RECESSIVE INHERITANCE
There are four different combinations
of the two genes from each parent
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
This child has inherited two copies of the normal gene - one from each parent
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
This child has inherited the normal gene from one parent but the altered gene from the other parent
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
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
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
This child has inherited the altered gene from
each parent
Parents
Gametes
Offspring
AUTOSOMAL RECESSIVE INHERITANCE
Which children are affected by the disease?
Parents
Gametes
AUTOSOMAL RECESSIVE INHERITANCE
AffectedUnaffectedUnaffected Unaffected
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
But …
what is the risk to a healthy sib of being a carrier for the recessive disease?
II:1John
Hobson
II:2ChristineHobson
III:1MervinHobson
III:2Alice
Hobson
III:3RichardHobson
I:1 I:2
II:3ChristopherWhitehead
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 homozygoteA 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 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
Disease Freq/1000 births
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.
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