Autosomal recessive inheritance: the basics a tutorial to show how the genes segregate to give the...

transcript

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

Parents

AUTOSOMAL RECESSIVE INHERITANCE

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

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

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

Parents

Gametes

There are four different combinations

of the two genes from each parent

Parents

Gametes

Offspring

This child has inherited two copies of the normal gene - one from each parent

Parents

Gametes

Offspring

This child has inherited the normal gene from one parent but the altered gene from the other parent

Parents

Gametes

Offspring

Parents

Gametes

Offspring

This child has inherited the altered gene from the

first parent and the normal gene from the

second parent

Parents

Gametes

Offspring

Parents

Gametes

Offspring

This child has inherited the altered gene from

each parent

Parents

Gametes

Offspring

Which children are affected by the disease?

Parents

Gametes

AffectedUnaffectedUnaffected Unaffected

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

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. (p.a.farndon@bham.ac.uk)

Autosomal recessive inheritance: the basics a tutorial to show how the genes segregate to give the...

Documents