Download How did I get this? Prenatal and neonatal screening Ultrasound

How did I get this?
Prenatal and neonatal screening
Ultrasound - www.youtube.com/watch?v=1X6kZdVBLkE
Heel prick test - www.youtube.com/watch?v=PFpsmWUsXDg
When a woman is pregnant, everyone hopes that the baby will be born healthy.
Unfortunately this is not always the case.
Sometimes the baby has some form of congenital disorder.
Such congenital disorders can be caused by external factors such as intake of alcohol, medication or
drugs, infectious diseases during pregnancy, or problems that develop during labour.
Such factors cause disorders in which the baby’s genetic information remains unchanged and which are
therefore not considered to be genetic disorders.
Congenital disorders can also be caused by changes in the genetic material, known as mutations.
Small-scale mutations result in a change in the DNA, while larger mutations lead to abnormal chromosome
structure or an abnormal number of chromosomes.
Congenital disorders caused by a mutation are known as genetic disorders.
The consequences of a mutation may already be visible at birth.
But sometimes, although the genetic predisposition is already present at birth, the disorder is not apparent
until many years later. A genetic disorder can be passed down to the child by the father and/or mother.
It is also possible for a new mutation to have been generated as a result of a mistake made during the
formation of the parents’ sex sells.
Prenatal (before birth) and neonatal (directly after birth) screening can be used to test the baby for
several disorders. For example, the chances of having a child with Down syndrome can be determined using
a nuchal translucency test (between the 11th and 14th week of pregnancy).
After birth, a drop of blood from the newborn baby’s heel can be used to test for a variety of genetic
disorders. PKU (phenylketonuria) was the first disorder to be detected using the heel prick test.
In the Netherlands, this test is currently used to screen for 17 different genetic disorders.
This module focuses on the different genetic disorders that can be detected during or directly after birth.
In the final step of this module you will investigate the causes and effects of one genetic disorder that can
be detected using the heel prick test.
For starters
Refresher test
1 a. In genetics, what do we mean when we say that a cell is 2n?
The cell has:
 Two pairs of chromosomes
 n pairs of chromosomes
 Two chromosomes
 Chromosomes with two chromatids
b. In humans, what is n?
 23
 46
 48
 92
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c. To which process does the following formula belong?
2n --> n + n
 Meiosis
 Mitosis
 Fertilisation
2. In humans, when does meiosis occur?
 During the formation of sex cells
 During growth and development
 When sex sells fuse together
 During cell differentiation
3. When is a person’s genotype determined?
 At birth
 At fertilisation
 As a result of environmental influences
 At the same time that the phenotype is determined.
4. In simple terms, the shape of the human earlobe is determined by two alleles. There is one
allele for free earlobes and one allele for attached earlobes.
Consider a woman who has free earlobes and is heterozygote for this genetic trait. Assuming
no mutations have taken place, which of the following cells definitely have the allele for
attached earlobes?
 A cell in the earlobe
 A cell in the ear bones
 An egg cell
5. When you compare the needles on a pine tree they are not all the same length. What can
you say about the needles’ phenotype and genotype?
 The phenotype and genotype are the same in all the needles
 Only the phenotype is different
 Only the genotype is different
 Both the phenotype and the genotype are different
6. Which statement about sex chromosomes is true?
 Sex chromosomes are found in all cells.
 Sex chromosomes are found only in sex cells.
 All the chromosomes in a sex cell are sex chromosomes.
 All the chromosomes in all the cells of the reproductive organs are sex chromosomes.
7. Which chromosomes are the autosomes?
 1 to 5
 6 to 22
 1 to 22
 23 (X and Y)
8. A child born to two healthy parents has a genetic disorder.
The allele for the genetic disorder comes from the parents.
The disorder is not X-linked.
Is inheritance of the disease dominant or recessive?
 Dominant
 Recessive
 Cannot be determined
9. Pregnancy tests are based on the detection of a hormone that is only produced at the start
of pregnancy.
What is the name of this hormone?
 Oestrogen
 Oxytocin
 Progesterone
 hCG
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10. A gene is a carrier of genetic information. What does a gene carry the code for?
 An amino acid
 RNA
 A protein
 DNA
Final product - Assessment
Final product
In the final step of this module you will investigate the causes and effects of a genetic disorder that
can be detected using the heel prick test. You will write a leaflet or give a presentation targeted at
primary school children who have a younger brother or sister with this disorder.
Assessment
To be discussed with your teacher.
Goals - Concepts
Learning goals
You know:
 the causes of several genetic congenital disorders
 three types of mutations
 the methods used in a number of prenatal screening techniques (combination test, amniocentesis
and chorionic villus sampling)
 several advantages and disadvantages of prenatal and neonatal screening
 what is and is not possible using prenatal and neonatal screening
 the phase of the cell cycle during which genome mutations take place (meiosis).
You can:
 identify genetic abnormalities in a human karyogram, e.g. trisomy
 construct a Punnett square for X-linked inheritance
 construct a pedigree for autosomal inheritance
 explain why older women have a higher risk of a child with Down syndrome
 write a leaflet or give a presentation about a genetic disorder.
 Extra: You can describe the different types of chromosome mutations.
Subconcepts
Chromosomes, gene, allele, phenotype, genotype, autosomes, sex chromosomes, dominant,
recessive, pedigree, point mutation (or gene mutation), chromosome mutation, genome mutation,
meiosis, mitosis, homologous chromosomes, karyotype.
Skills
A1 Information-seeking strategies
A2 Communicating
A5 Investigating
A14 Reasoning in terms of systems
Method
Format
In this module you will work individually or in groups of 2. Ask your teacher whether you should complete
the extra assignments in steps 4 and 5.
For the final assignment in step 7, you will make the leaflet or give the presentation in groups of 2.
Time required
For this module you will need 8-10 hours.
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GET TO WORK!
Step 1
Prenatal screening
In the Netherlands, pregnant women usually receive care from a midwife, sometimes from an obstetrician.
The midwife or obstetrician will always offer the mother an ultrasound scan to check the normal
development of the foetus and its organs. In an ultrasound, sound waves and a computer are used to
construct an image of the foetus.
Information about the foetus’ length, together with the date of the first day of the woman’s last menstrual
period, can be used to calculate the estimated delivery date.
Prenatal screening includes those tests carried out during pregnancy that go further than the ‘regular’
ultrasound scan. Prenatal screening is done during pregnancy to determine whether or not the child has
an increased risk of having a congenital disorder. Chromosomal tests and DNA tests can be done to
determine whether the unborn child has certain genetic disorders.
Techniques
Various techniques are used in prenatal screening. In the Netherlands, pregnant women have the option of a
more extensive ultrasound scan at 20 weeks. The main purpose of the 20-week ultrasound is to check
for possible spina bifida and to make sure the baby’s organs (e.g. heart and kidneys) are developing
properly. The midwife will also check that the baby is growing properly, whether there is enough amniotic
fluid and, if so desired, whether it is a boy or a girl.
Pregnant mothers can also choose to have the so-called combined test done. The combined test is
performed to test for the risk of having a baby with Down syndrome. The test consists of a combination of
a blood test and an ultrasound scan (nuchal translucency test).
Chorionic villus sampling and amniocentesis are both tests which assess cells withdrawn from the
foetus. In the Netherlands these tests are only performed in the following cases:
 In women aged 36 or older, since the risks of chromosomal abnormalities are known to increase with
increasing maternal age. You will find out more about this in step 4.
 In women who have already had a child with a chromosomal abnormality.
 If there are any close relatives who have a genetic disease or chromosomal abnormality (that can be
detected with these tests).
Assignment 1
First study the reference material, then answer the following questions about the combined test:
a. Which hormone is measured in the blood test and what conclusion can you draw from the
results?
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
b. In the nuchal translucency test, what is an indication of a higher risk of Down syndrome?
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
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Reference material:
Blood test - www.studiobiologie.nl/havo_bb/CARIBBEAN/How%20did%20I%20get%20this/Blood_test.doc
Nuchal translucency test - pregnancy.healthguru.com/video/understanding-the-nuchal-test
Increased nuchal translucency - www.youtube.com/watch?v=9U32mfBMa-o
Assignment 2
For this assignment you will work in groups of 2. Each of you will study one type of prenatal screening:
chorionic villus sampling or amniocentesis.
For this you should use your textbook, the reference material provided below and, if necessary, other
sources.
Answer the following questions:
 What does the test involve? How is data collected?
 During which period of pregnancy is the test carried out?
 What conclusions can be drawn from the data? Which disorders can be detected using the test?
Name at least two.
 For which women is the test most suited?
 What are the pros and cons of this screening technique?
Exchange your answers with your partner.
Reference material:
How does chorionic villus sampling work? - video.about.com/pregnancy/Chorionic-Villus-Sampling.htm
Chorionic villus sampling - www.youtube.com/watch?v=sxEf_ddmpZk
What is an amniocentesis? - www.youtube.com/watch?v=Ly9Xe85FDVU
Amniocentesis - americanpregnancy.org/prenataltesting/amniocentesis.html
Amniocentesis: Amniotic fluid test in pregnancy - www.youtube.com/watch?v=bZcGpjyOXt0
Step 2
Genetic disorders
From this step onwards you will focus on the different genetic disorders that can be detected using prenatal
and neonatal screening. The different types of changes in the genetic material (mutations) are as follows:
1. Genome mutations: abnormalities in the number of chromosomes;
the total number of chromosomes per cell deviates from the normal number; you will find out more about
this in steps 5 and 6.
2. Chromosome mutations: abnormalities in the structure of the chromosomes; you will find out more
about this in step 4.
3. Point mutations: abnormality in the DNA of a single gene; steps 2 and 3 are about point mutations.
Genome mutations and chromosome mutations
Genome mutations and chromosome mutations are also known as chromosomal abnormalities. This is
the same thing as a chromosomal anomaly or chromosomal aberration.
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Haemophilia − bad news for boys
Haemophilia (type A or B) is a genetic disease that prevents the blood from clotting properly. The cause of
both types of haemophilia is a point mutation in the genetic material. Haemophilia is seen in boys, but
hardly ever in girls. Why is this?
Assignment 1
a. What are the symptoms of haemophilia?
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
b. The gene for haemophilia is found on chromosome pair number 23.
What name is given to this pair of chromosomes?
………………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………………
c. The allele for haemophilia is X-linked recessive. What does this mean?
Use the following words in your answer:
sex chromosome, carrier, heterozygote, homozygote, sex-linked inheritance.
d. Complete the Punnett square below to show how two healthy parents can still have a child with
haemophilia. Use the letter XH for the dominant allele and the letter Xh for the recessive allele.
Then write the phenotypes in the correct position.
Xh Y - XH XH - XH Xh - XH Y - healthy – healthy – haemophilia – carrier
Mother is a carrier
Healthy
father
XH
Xh
XH
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
Y
e. What are the chances of the parents having a healthy child?
 0%
 25%
 50%
 75%
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f. For the following sets of parents, complete the three Punnett squares and determine the genotypes and
phenotypes of their possible children (choose between healthy, carrier and haemophilia):
I. A father with haemophilia and a healthy (homozygote) mother have children.
II. A healthy father and a mother with haemophilia have children.
III. A healthy father and a mother who is a carrier have children.
I
Healthy mother
Father with
haemophilia
XH
XH
Xh
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
Y
II
Mother with haemophilia
Healthy
father
Xh
Xh
XH
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
Y
III
Mother is a carrier
Healthy
father
XH
Xh
XH
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
………………………………………
……………………………………………
Y
g. In which exceptional case will a daughter inherit haemophilia from her parents?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
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h. Why is it that more boys than girls have haemophilia?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
………………………………………………………………………………………………………………………………………………………………………………………………….......................................
Assignment 2
a. This pedigree shows the inheritance of haemophilia in a famous family. How can you tell by looking at
the pedigree that haemophilia is a recessive disorder?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
b. How can you tell that haemophilia is passed on via the X chromosome?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
Haemophilia is an X-linked recessive disorder. If you hadn’t guessed already, it is also possible to have
an X-linked dominant disorder, e.g. Rett syndrome.
More information:
www.rettsyndrome.org/understanding-rett-syndrome/about-rett-syndrome/what-is-rett-syndrome
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Step 3
PKU and the heel prick test
Not all diseases are passed on by the X chromosome. In autosomal inheritance the point mutation
is not on one of the sex chromosomes but on one of the other pairs of chromosomes. Some genetic
disorders develop when the child has inherited a mutated gene from one parent, even if it inherits
the normal gene from the other parent. This is called autosomal dominant inheritance.
When a genetic disorder is caused by two mutated genes coming together, this is called autosomal
recessive inheritance.
Take a look at the video clips:
PKU - www.youtube.com/watch?v=KUJVujhHxPQ
Neonatal heel prick www.rivm.nl/Bibliotheek/Algemeen_Actueel/Multimedia/Preventie_Ziekte_Zorg/hielprik
PKU is the abbreviation of phenylketonuria, a disease in which the enzyme phenylalanine hydroxylase
(PAH) is either absent or deficient. The absence of this enzyme means that the amino acid
phenylalanine cannot be broken down properly. This can lead to a variety of symptoms. If there is a
chance that a pregnant woman may give birth to a child with PKU, she can undergo prenatal
screening. The heel prick test in newborn babies (i.e. neonatal) also helps to prevent much
suffering. The sooner the disorder PKU is detected the better.
Assignment 1
a. Which nutrients are people with PKU unable to digest properly?
 fats
 proteins
 carbohydrates
b. Too much phenylalanine in the blood can cause various symptoms. What are the symptoms of PKU?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
c. How do people with PKU prevent a build-up of phenylalanine in their blood?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
d. On which chromosome is the gene for phenylalanine hydroxylase (PAH) found?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
e. What type of inheritance applies to the PAH gene?




Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
f. Calculate the chances of two healthy parents having a child with PKU.
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
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Assignment 2
Work in groups of 2 and divide the tasks between you.
a. Search together for examples of genetic disorders that belong to each of
the four types of inheritance.
b. For each type of inheritance, draw an example of a pedigree.
Use the symbols indicated in the key and write down each person’s genotype.
Reference material:
 Leaflet on dominant inheritance www.studiobiologie.nl/havo_bb/CARIBBEAN/How%20did%20I%20get%20this/Word/Domina
nt_Inheritance.pdf
 Leaflet on recessive inheritance www.studiobiologie.nl/havo_bb/CARIBBEAN/How%20did%20I%20get%20this/Word/Recessi
ve_Inheritance.pdf
 Leaflet on X-linked inheritance www.studiobiologie.nl/havo_bb/CARIBBEAN/How%20did%20I%20get%20this/Word/X_linke
d.pdf
Step 4
Cri du chat – a mistake on chromosome 5
Take a look at this video clip:
International Cri Du Chat Syndrome Awareness www.youtube.com/watch?v=La1D4cNQ5kQ
Cri-du-chat (cry of the cat) syndrome is a congenital disorder in
which part of chromosome 5 is missing. This is what is known as a
chromosome mutation. Babies born with cri-du-chat syndrome
often have a low birth weight and a characteristic cry that sounds
like a cat. This is how the syndrome got its name.
The children often have a small head and narrow jaw, low-set ears
and wide-set eyes. They sometimes have feeding problems, heart
defects or fingers or toes that are fused together. The degree to
which these features occur, if at all, differs from person to person.
When a child is born with cri-du-chat syndrome they are usually the
first in their family to have it (new mutation). The chances of the
parents having another child with this syndrome are about one in
100 (1%).
Karyogram
A karyotype or karyogram is a picture of the chromosomes as seen
under a microscope during a certain stage of cell division.
A karyogram can be used to detect chromosomal abnormalities
(e.g. with regard to number or structure).
Assignment 1
a. Compare the karyograms of a healthy person and a person
with cri-du-chat syndrome. Where can you see a difference?
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b. In the following passage, fill in the gaps using the same or different:
Two homologous chromosomes have ………………………………………………… structure/structures but are not identical.
They have ………………………………………………… genes at ………………………………………………… place/places.
The genetic information is …………………………………………………, because the alleles are ………………………………………………….
Chromosome pair number 5 usually consists of two homologous chromosomes.
This is not the case in cri du chat.
c. When did this mutation occur?
 The mutation occurred in meiosis during sex cell formation.
 The mutation occurred during fertilisation of the egg cell by a sperm cell.
 The mutation occurred during mitosis (normal cell division) in the foetus.
 At birth.
Extra assignment
In cri-du-chat syndrome there is a mutation in the structure of a chromosome.
There are different types of chromosome mutations, as shown in the diagram.
The chromosome mutation in cri-du-chat syndrome is a deletion.
Look for an example of each of the other chromosome mutations.
Step 5
Trisomy – an extra helping
In diploid organisms, with the exception of the sex chromosomes, the chromosomes are normally in
pairs (homologous chromosomes).
When an individual is missing one chromosome from a pair of chromosomes, this is known as
monosomy. When an individual has an extra copy of a chromosome, this is known as trisomy.
In both cases there is an abnormal number of chromosomes, which is why they are known as
genome mutations. The mother’s age can affect the generation of genome mutations, as seen in
Down syndrome. Why is this?
Assignment 1
Study the structure and development of sex cells in men and women, either by reading your
textbook or by taking a look at the following video clips:
Female sex cells - education-portal.com/academy/lesson/oogenesis-how-the-female-reproductivesystem-produces-eggs.html
Male sex cells - education-portal.com/academy/lesson/spermatogenesis-how-the-male-reproductivesystem-produces-sperm.html
a. Men can still have children when they get older, while women cannot.
Explain this difference in fertility on the basis of how male and female sex cells develop.
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
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In the Netherlands, the average age at which women have a baby
has increased in recent decades. Take a look at the graph.
b. What realistic explanations might there be for women in the
Netherlands having their first child later? Exchange your answers
with a classmate.
Women
Putting off motherhood is not equally widespread in all layers of
society. Highly educated women and women living in big cities are
more likely to have a child later.
Assignment 2
a. What are the physical features (phenotype) of someone with Down syndrome?
Name at least four features.
b. Compare these two karyograms.
What is the difference between a healthy individual and someone with Down syndrome?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
c. Is this person with Down syndrome a man or a woman?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
Assignment 3
The chances of having a child with Down syndrome increase as the mother gets older.
a. Although the chances of having a child with Down syndrome are higher in older mothers, most
children with this disorder are born to young mothers. Explain this difference.
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Down syndrome can occur when something goes wrong during egg cell development.
Study meiosis and the development of sex cells, by either reading your textbook or taking a look at
the following video clips:
Female sex cells - education-portal.com/academy/lesson/oogenesis-how-the-female-reproductivesystem-produces-eggs.html
Male sex cells - education-portal.com/academy/lesson/spermatogenesis-how-the-male-reproductivesystem-produces-sperm.html
Biology: Meiosis – cell division - www.youtube.com/watch?v=kVMb4Js99tA
b. What causes trisomy 21? Describe what goes wrong during meiosis, and then during fertilisation
of the egg cell by the sperm cell. You can include drawings in your answer!
Check your answer here: ccmctraining.com/peds_html_fixed/peds/genetics/happen.htm
Extra assignment
In the Netherlands, as of 1 April 2011, prenatal screening for Down syndrome has been extended.
Parents who choose to undergo Down syndrome screening will often also be told whether their child
has a higher risk of trisomy 13 (Patau syndrome) or trisomy 18 (Edwards syndrome).
Find out what is wrong in people who have these two syndromes.
Step 6
Man, woman or a bit of both?
In step 4 you found out what happens when autosomes are not properly distributed over the sex
sells. If this happens with the sex chromosomes then this affects the sexual development of the
individual.
Assignment 1
Take a look at this video clip about women with Turner syndrome:
Woman and girls with Turner Syndrome - www.youtube.com/watch?v=8ObFJ3DnV04
a. Turner syndrome is an example of monosomy in the sex chromosomes.
The karyogram of a woman with Turner syndrome is shown here. What is wrong?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
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Karyogram 45,XO
b. What causes Turner syndrome in women?
Karyogram 47,XXY
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
c. Klinefelter syndrome occurs only in men. Men with Klinefelter syndrome have at least one extra X
or Y chromosome. So they do not have 46 chromosomes, but 47 or more. The most common
variation is 47,XXY. But an individual may also have 48,XXXY or 48,XXYY or even 49,XXXXY. What
causes 47,XXY?
…………………………………………………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………………………………………………
Step 7
Final assignment
You are about to start work on the final assignment.
You should work in groups of 2. Choose one of the genetic disorders that can be detected using the
heel prick test, e.g. sickle cell disease.
Take a look at this video clip:
Disease and mutation: Sickle cell - www.dnalc.org/resources/3d/17-sickle-cell.html
Choose from one of the following for your final product:
 an informative leaflet
 an oral presentation
The target group is primary school children who have a younger brother or sister with this disorder.
The leaflet should contain information about the symptoms of the disease, about how it is inherited
(example of a pedigree) and about how it can be cured or how its symptoms are treated.
Discuss with your teacher the requirements of the leaflet or presentation.
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