Genetic Diseases and Genetic Counselling

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GHB 2005

Every gene carries information telling the body how to make a particular protein

Adult cells have two copies of each gene, so…

…if one copy of the gene doesn’t work, the cell has a ‘backup’

New versions of genes can be produced by …

…mutation.

These new versions or… alleles...

…can produce proteins that either:

- do not work, or- do something which they are not supposed to do

These defective genes can cause serious ……genetic diseases

Example: Cystic fibrosisThe cell membranes of the cells lining the lungs and air passages contain CF membrane proteins

Cell membrane CF membrane proteins

The CF protein pumps chloride ions from one side of the membrane to the other

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The CF protein produces a higher concentration of chloride ions on one side of the membrane than the other

…osmosis.

H2OH2O

H2O

Cell membrane

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Water molecules follow the chloride ions across the semi-permeable cell membranes by…

H2OH2O

H2O

The body uses the CF chloride pump to move water into secretions like the mucus found in the trachea and sweat.

If your cells cannot make working chloride pumps, your mucus becomes too thick and sticky due to lack of water

However, to make a functioning chloride pump, each cell only needs one good copy of the gene for it.

So, cystic fibrosis is recessive

Cc

Defective gene produces non-working chloride pump

Healthy gene produces working chloride pump

This individual does not suffer from cystic fibrosis,but is a carrier

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c c

This individual will suffer from cystic fibrosis

REMEMBER: Genes do NOT exist to cause disease…

… defective genes cause disease

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Neither copy of the gene carried by this individual can produce a working chloride pump

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Length of DNA

How are genes switched on and off?

You do not want nerve cells making liver cell proteins

Cells only use some of their genes most of the time

Most genes can be switched on or off

Example

Operator region Structural region (code for protein)

Gene

Repressor binding site

RNA polymerase binding site

Repressor protein

Repressor protein attaches itself to its binding site…

RNA polymerase

The enzyme RNA polymerase attaches itself to its binding site…

… and moves down the strand of DNA decoding the gene

ON

OFF

RNA polymerase is blocked and cannot attach to DNA

There is nothing to stop DNA polymerase binding… ON

If the repressor binding site is lost…

… the repressor protein cannot bind to the DNA

… so the gene is permanently

Having a healthy copy of this gene will not switch the defective copy off, so…

… the disease caused by the defective allele is… … dominant

Genetic Counselling

A genetic counsellor advises couples on the likelihood of their children having a particular genetic disease.

The genetic counsellor considers:

- how common the gene is in the general population

e.g. 1 in 17 people in the UK are carriers for cystic fibrosis

- the two family trees of the couple

i.e. can they work out the genotype of the couple?

- the results of genetic tests

Looking at Family Trees

Unaffected male

Unaffected female

Affected male

Affected female

Carriers -

unaffected heterozygotes

Sex not known

?Male of unknown genotype/phenotype

Dead

mating

consanguineous mating(Kept it in the family)

Parents with son and daughter

Oldest to youngest shown left to right

Parents with son and twin daughters

Identical twins

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The pedigree below shows a family with a history of a rare genetic disease

Is the disease recessive or dominant?Explain you answer

The disease is recessive:- It skips generations- Carriers have the gene

but are not affected

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Assume that A, B, C and D do not suffer from the disease – what is their genotype? Explain your answer.

All four are heterozygous carriers.-C&D must be carriers to produce offspring with the disease- D must have inherited the gene from B, and C from A.

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A B

C D ??

What are genotypes and phenotypes of X and Y?

Both are heterozygous carriers.- they must inherit a copy of the disease allele from their father- they must inherit the healthy allele from their mother

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A B

C D ??X Y

1:2 or 50%:- He must inherit the healthy allele from his father- He has a 50% chance of inheriting the disease gene from his carrier mother

What are the chances of Z being a carrier?

Z?

A B

C D

X Y

Z?

A B

C D

X Y

Z is concerned that any children that he may have will suffer from the disease. What advice would you give him?

1. If possible, get himself tested to see if he is a carrier

- If he is not a carrier, the probability of his children being sufferers is 0

2. Try to marry outside the family- An unrelated person is less likely to be a carrier

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A

B

C

ED F

K L

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The pedigree below shows another family with a history of a genetic disease

Is the disease dominant or recessive? Explain your answer

This disease is dominant:-It is passed from A to E & F without skipping a generation -(there are no carriers)-It can be inherited from only one parent

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A

B

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ED F

K L

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Y

What is K’s phenotype and genotype? Explain your answer

K is unaffected (homozygous recessive)

K must have same genotype and phenotype as twin, L

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A

B

C

ED F

K L

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Y

What are X and Y’s phenotype and genotype? Explain your answer

X and Y are both affected (heterozygous)

- Both must have carried gene for Z to have inherited it

- Both will have inherited the normal alleles from their mothers

Z

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A

B

C

ED F

K L

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Y

E is concerned that any children she has will be affected. What would you advise her?

Z

Probability of any child being affected is1:2 or 50%:- they must inherit the healthy allele from F- they have a 50% chance of inheriting the disease gene from E