2021-22
BBT 2 – Clinical Genetics
Answer Sheet
STUDENT NAME: ………………………………………………………………..
GROUP/ KCL NUMBER: ………………………………………………………..
DATE: ……………………………………………………………..
………………. Vivanco, Igor
BBT 2 – Clinical Genetics
Formative Assessment:
This formative assessment will not count towards the final mark for your BBT module. It
nevertheless constitutes an essential part of the overall learning process and should be taken
seriously.
Aims of this assessment:
1. Acquire knowledge and skills which will help you in the following years when you come
to write summative assessments.
2. Allows you to try out various ideas and get feedback on them without having to worry
about the mark counting towards your final grade.
3. A chance to hand in a piece of work that will be marked according to the same criteria
and plagiarism rules as your summative coursework. This can then give you an accurate
awareness of what is expected from you as well as what is required to attain a particular
grade.
Notes:
Read carefully the questions
Write your answers in the boxes provided.
Do not write outside of the boxes.
Any answers outside of the boxes will be ignored and will reduce your final mark.
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BBT 2 – Clinical Genetics
Activity 1 – Drawing a Pedigree (20 marks)
Q1. In the space below, draw a pedigree which complies with standard rules for a family where
grandma had sickle cell anaemia and yet survived long enough to have two children, a girl and
a boy. Neither of her children had sickle cell anaemia. The son married and produced a boy who
also did not have sickle cell anaemia. The daughter also married and had three children, two
girls and boy. However, one of her daughters and her only son had sickle cell anaemia. (5
marks)
Q2. What can we tell about the genetic inheritance of sickle cell anaemia by looking at this
pedigree? Explain briefly your reasoning. (15 marks)
Sickle cell anemia is a autosomal recessive inheritance. This can be deduced as
the daughter married an unaffected man. Two of their children (one daughter and
the son) have sickle cell anemia, meaning the parents were carriers and if were
carriers that means the gene was recessive.
Grandmother was homozygous recessive.
Grandmothers’ son is heterozygous as well as the daughter.
The daughter’s partner is also heterozygous
but the son’s partner is homozygous dominant
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BBT 2 – Clinical Genetics
Activity 2 – The Law of Segregation (40 marks)
Q1. In light of the Law of Segregation and the information in your pedigree, what type of trait do
you think that sickle cell anaemia is? Please select (underline) one of the following answers and
briefly explain your choice in the box provided below. (10 marks)
a) Dominant trait
b) Recessive trait
c) Incompletely dominant trait
Explanation:
Based on the law of segregation, each parent contributes one allele for a
given gene to their offspring. For sickle cell anaemia to affect someone,
an individual must inherit two recessive alleles (ss) one from each parent.
The affected individuals (grandma, one granddaughter, and one
grandson) are only affected when both parents contribute the recessive
allele. Carriers (Ss) do not exhibit the disease, meaning that two
recessive alleles are needed for the disease to manifest. The condition
skips generations when carriers (heterozygous individuals) reproduce
without passing two defective alleles.
Q2. Draw a Punnett square for the mating union between Grandma’s daughter and her partner.
To remind yourself of what a Punnett square is, Dr Panaretou gave an example on slide 23 of
his first lecture. In your nomenclature, assign the wild-type β- globin gene the symbol A and the
mutated β-globin gene the symbol S. Using this nomenclature, the genotype of someone who is
homozygous wild-type will be AA and will not suffer from the disease. Likewise, someone who is
homozygous mutated will be SS and will suffer from the disease. Finally, someone who is
heterozygous will be AS or SA and will be a carrier of the disease. (8 marks)
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BBT 2 – Clinical Genetics
Q3. Grandma’s daughter has a fourth child still in the womb. What are the odds that the
outcome of the pregnancy is (a) homozygous wild-type, (b) heterozygous, (c) homozygous
disease? (2 marks)
a. 25% b. 50% c. 25%
Q4. Does the actual mating outcome (two out of three children with sickle cell disease) match
the predicted outcome from the Punnett square? If they do not match, explain why this is the
case. (10 marks)
According to the Punnett square, the probability of having a child with sickle
cell disease (SS) is 25%.
The actual outcome is that 2 out of 3 children have sickle cell disease, this
means there is a difference. This difference can be due to small sample size
or mutations. The punnet square gives you data for a large sample size but
we only have 3 kids so not a large enough pool of children.
Q5. What are the clinical issues associated with being heterozygous? Please structure your
answer in bullet points and do not exceed the space provided. (10 marks)
1. Heterozygous individuals (AS) usually do not show symptoms of sickle cell
anaemia, as they have one normal (A) and one mutated (S) gene.
2. Individuals are carriers of the sickle cell gene and can pass it on to offspring,
potentially leading to the birth of affected children (SS) if the partner is also
a carrier
3. Although rare, some carriers may develop sickle cell-related complications
under extreme stress or specific health conditions, such as pregnancy-
related complications, anemia, or during extreme dehydration
4. Carriers also have a high risk of certain conditions such as autosomal
disorders defects or autosomal disorders
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BBT 2 – Clinical Genetics
Activity 3 – the Effect of Malaria upon Sickle Cell Anaemia
(40 marks)
Part A (25 marks)
Q1. What do you think will happen to the frequencies of the A and S alleles as a result on the
presence of malaria? Please choose your answer bellow (underline) and formulate a hypothesis
and corresponding prediction for the future generations, and explain your reasoning in the
boxes below. (10 marks)
a. Frequency of A allele increase
b. Frequency of S allele increase
c. Frequency of alleles remains the same
Hypothesis: In regions where malaria is widely seen, the frequency of the S allele
(which causes sickle cell trait) is likely to increase over time due to the higher
chance of survival
Reasoning: People who are AS (heterozygous carriers) are less likely to suffer from
malaria compared to those who are homozygous (AA), which makes them more
likely to survive and reproduce in malaria-endemic areas.
Over generations, the S allele would increase in frequency because heterozygous
carriers (AS) have a reproductive advantage in malaria-prone environments
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BBT 2 – Clinical Genetics
Q2. What do you think “allele frequency” means, and how do they relate to evolution? (10
marks)
Allele frequency is the percentage of a specific version of a gene in a population.
Natural selection occurs when certain alleles provide a survival advantage in a
particular environment, leading to those individuals having greater reproductive
success. Over time, the frequency of the advantageous allele increases in the
population, while disadvantageous alleles decrease. There are other factors that
also increase alleles such as mutations and there other factors that also decrease
alleles like genetic drift.
Q3. What are the selective forces – the forces which change the allele frequencies – in this
simulation? (5 marks)
Natural Selection
Genetic Drift
Gene Flow
Mutation
Sexual Selection
Part B (15 marks)
Results of the randomized selection on-line experiment
Table 1: First Generation (F1) Tally Chart
Group Tally Total
AA 29
AS 17
SS 4
Non-surviving 17
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BBT 2 – Clinical Genetics
Table 2: F1 Total Surviving Alleles
43
Number of A alleles surviving (count out of AA and AS groups)
17
Number of S alleles surviving (count of out of AS group)
Table 3: Second Generation (F2) Tally Chart
Group Tally Total
AA 15
AS 13
SS 2
Non-surviving 9
Table 4: F2 Total Surviving Alleles
Number of A alleles surviving (count out of AA and AS groups) 29
Number of S alleles surviving (count of out of AS group) 13
Table 5: Final Results
Parents F1 F2
A S A S A S
Total 75 25 43 17 29 13
Allele 75/100 25/100 43/60 17/60 29/42 13/42
frequency
Q4. Based on the results, what was the general trend for allele A over the three generations?
What was the general trend for allele S over the same period of time? Was your hypothesis
supported? Justify your reasoning. (5 marks)
Over the three generations, the frequency of allele AAA decreased (from 3/4 to 43/60 to 29/42),
while the frequency of allele SSS increased (from 1/4 to 17/50 to 13/42). This trend supports
the hypothesis that the S allele's frequency would rise due to the selective advantage of AS
individuals in malaria-endemic regions. The changes in allele frequencies result from the
differential survival and reproductive success of the genotypes under selective pressures
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BBT 2 – Clinical Genetics
Q5. Do you anticipate that the trends you have observed will continue for many generations?
Explain your reasoning. (5 marks)
Yes, I anticipate that the trends observed will continue for many generations,
especially in regions with high amount of malaria because Heterozygous
individuals (AS), who carry one copy of the S allele, have a survival advantage in
regions with malaria because they are resistant to malaria. They are more likely to
survive to reproduce compared to AA individuals. Because of this advantage, AS
individuals are more likely to reproduce and pass on the S allele to their offspring,
increasing the frequency of the S allele in the population.
Q6. Since few people with sickle cell anaemia (SS) are likely to survive to have children of their
own, why hasn’t the mutated allele been eliminated? (5 marks)
Individuals who are heterozygous (AS) for the sickle cell trait have one normal
allele (A) and one mutated allele (S). These individuals do not suffer from sickle
cell disease but have increased resistance to malaria compared to those with two
normal alleles (AA). In regions with malaria this provides a significant survival
advantage and so, the S allele remains in the population, even though
homozygous individuals (SS) suffer from sickle cell disease and have reduced
survival rates.
