Transcript Genetic Disorders and Pedigree

Genetic Diseases
and Genetic
Counselling
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A
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Z
X
Y
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 fibrosis
The cell membranes of the cells lining the lungs and air
passages contain CF membrane proteins
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Cell membrane
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CF membrane
proteins
The CF protein pumps chloride ions from one side of the
membrane to the other
The CF protein produces a higher concentration of chloride
ions on one side of the membrane than the other
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Cell membrane
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Water molecules follow the chloride ions across the semipermeable cell membranes by… …osmosis.
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
c
Defective gene
produces non-working
chloride pump
C
Healthy gene
produces working
chloride pump
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This individual does not
suffer from cystic fibrosis,
but is a carrier
Neither copy of the
gene carried by this
individual can
produce a working
chloride pump
c
c
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This individual will
suffer from cystic
fibrosis
REMEMBER: Genes do NOT exist to cause disease…
… defective genes cause disease
How are genes switched on and off?
Cells only use some of their genes most of the time
You do not want nerve cells making liver cell proteins
Most genes can be switched on or off
Example
Gene
Length of
DNA
Operator region
Repressor
binding site
Structural region
(code for protein)
RNA polymerase
binding site
The enzyme RNA polymerase attaches
itself to its binding site…
ON
RNA polymerase
… and moves down the
strand of DNA decoding the
gene
Repressor protein attaches itself to its
binding site…
OFF
Repressor
protein
RNA polymerase is blocked
and cannot attach to DNA
If the
repressor
binding site
is lost…
There is nothing to stop
DNA polymerase
binding…
… the repressor
protein cannot
bind to the DNA
… so the gene is
permanently
ON
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
Affected male
Unaffected female
Affected female
Sex not known
Carriers unaffected
heterozygotes
?
Male of unknown
genotype/phenotype
mating
Dead
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
The pedigree below shows a family with a history of a rare
genetic disease
Is the disease recessive or
dominant?
Explain you answer
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The disease is recessive:
- It skips generations
- Carriers have the gene
but are not affected
Assume that A, B, C and D
do not suffer from the
disease – what is their
genotype? Explain your
answer.
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C
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A
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D
B
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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.
What are genotypes and
phenotypes of X and Y?
B
A
C
D
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X
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
What are the
chances of Z being
a carrier?
B
A
C
D
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Z
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
Z is concerned that any
children that he may
have will suffer from the
disease. What advice
would you give him?
A
C
B
D
?
Z
1. If possible, get himself
tested to see if he is a
carrier
X
- 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
Y
The pedigree below
shows another
family with a history
of a genetic disease
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Is the disease dominant
or recessive? Explain
your answer
A
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X
B
Y
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C
K
D
E
F
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
L
What is K’s phenotype
and genotype? Explain
your answer
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A
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X
B
Y
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C
K
D
E
F
K is unaffected (homozygous recessive)
K must have same genotype and phenotype as twin, L
L
What are X and Y’s
phenotype and
genotype? Explain your
answer
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A
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X
B
Y
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C
K
Z
D
E
F
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
L
E is concerned that any
children she has will be
A
affected. What would you
advise her?
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X
B
Y
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C
K
Z
D
E
F
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
L