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YOUR NOTES
International AS Biology Edexcel 

Inheritance

CONTENTS
2.14 Mutations
2.15 Patterns of Inheritance & Sex Linkage
2.16 Cystic Fibrosis
2.17 Genetic Screening
2.18 Ethical & Social Issues of Genetic Screening

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2.14 Mutations YOUR NOTES


Nature of Mutations
A gene mutation is a change in the sequence of bases in a DNA molecule
Mutations may result in an altered polypeptide; as the DNA base sequence of a gene
determines the sequence of amino acids that make up a polypeptide, mutations in a gene
can sometimes lead to a change in the polypeptide that the gene codes for
Mutations occur spontaneously during DNA replication
There are different ways that a mutation in the DNA base sequence can occur, e.g.
Substitution
Insertion
Deletion
Substitution, insertion, and deletion mutations are all examples of point mutation;
mutations that involve a change in the DNA base sequence at a single location
Other types of mutation can affect entire genes or entire chromosomes
Genes can be replicated or lost
Chromosomes can be divided unequally during meiosis, resulting in cells with extra or
missing chromosomes
Substitution of nucleotides
A mutation that occurs when a base in the DNA sequence is randomly swapped for a
different base
A substitution mutation will only change the amino acid for the triplet in which the
mutation occurs, and will have no impact on triplets located elsewhere in the gene
Substitution mutations include
Silent mutations
The mutation does not alter the amino acid sequence of the polypeptide; this is
due to the degenerate nature of the genetic code
Missense mutations
The mutation alters a single amino acid in the polypeptide chain, e.g. sickle cell
anaemia is caused by a single substitution mutation changing a single amino acid
in the haemoglobin protein
Nonsense mutations
The mutation creates a premature stop codon, causing the polypeptide chain
produced to be incomplete and therefore affecting the final protein structure and
function, e.g. cystic fibrosis can be caused by a nonsense mutation
Note that a stop codon provides a signal for the cell to stop translation of
the mRNA molecule into an amino acid sequence

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YOUR NOTES


Substitution mutations involve swapping one nucleotide for another

Insertion of nucleotides
A mutation that occurs when a nucleotide is randomly inserted into the DNA sequence is
known as an insertion mutation
An insertion mutation changes the amino acid that would have been coded for by the
original base triplet, as it creates a new, different triplet of bases
Remember that every group of three bases in a DNA sequence codes for an amino acid
An insertion mutation also has a knock-on effect on other base triplets by changing the
triplets further on in the DNA sequence
This means that insertion mutations cause what is known as a frameshift
mutation; they don't only change the triplet where the insertion has occurred, but
every triplet downstream of the insertion
This may dramatically change the amino acid sequence produced from this gene and
therefore the ability of the polypeptide to function

Insertion mutations occur when a new nucleotide is added into a base sequence
Deletion of nucleotides

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A mutation that occurs when a nucleotide is randomly deleted from the DNA sequence YOUR NOTES
Like an insertion mutation, a deletion mutation changes the triplet in which the deletion 
has occurred, and also changes every group of three bases further on in the DNA
sequence
This is known as a frameshift mutation
This may dramatically change the amino acid sequence produced from this gene and
therefore the ability of the polypeptide to function

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Effects of Mutations YOUR NOTES

Most mutations do not alter the polypeptide or only alter it slightly so that its appearance 
or function is not changed
This is possible because the genetic code is degenerate; the base sequence can be
changed without necessarily altering the amino acid
However, a small number of mutations code for a significantly altered polypeptide
A mutation changes the DNA base sequence
One or many amino acids in the primary structure of a protein is altered
Different bonds form in the secondary and tertiary structures of the protein
The final 3D structure of the protein is altered
Very rarely this can give rise to a protein that provides an organism with an advantage, e.g.
resistance to an antibiotic, or the ability to digest a new type of food
Mutations that provide an advantage can drive the process of evolution by
causing natural selection to occur
Individuals with an advantage are more likely to survive and reproduce
The advantageous mutation is more likely to be passed on
The mutation becomes more common in the population
More often, mutations that affect polypeptide structure are likely to be harmful, affecting
the ability of proteins to perform their function, e.g.
In cystic fibrosis, a membrane channel protein no longer functions
A fault in the CFTR gene leads to production of non-functional chloride
channels, reducing the movement of water by osmosis into cell secretions
This results in the production of thick, sticky mucus in the air passages, the
digestive tract and the respiratory system
In sickle-cell disease, the haemoglobin protein no longer functions
Sickle-cell disease is caused by a single substitution mutation that causes
haemoglobin proteins to clump together
This affects the shape of red blood cells, preventing easy blood flow and causing
severe pain and problems with blood supply to important organs

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YOUR NOTES


Sickle cell disease is caused by a single substitution mutation that changes one amino acid
in the haemoglobin protein
Mutations in the genes that are involved with cell division can lead to uncontrolled cell
division and the development of tumours that can become cancerous
Mutations that occur in the gametes, or sex cells, can be passed on to future generations,
meaning that every cell in the body of an organism's offspring will contain the mutation
Mutagens can increase the likelihood of a mutation occurring, e.g.
Ionising radiation
X-rays
Some chemicals

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2.15 Patterns of Inheritance & Sex Linkage YOUR NOTES


Key Terms: Genetics
Genes & alleles
A chromosome is a long DNA molecule which contains many genes
A gene is a length of DNA that codes for a single polypeptide
The position of a gene on a chromosome is its locus (plural loci)
Each gene can exist in two or more different forms called alleles
Different alleles of a gene have slightly different nucleotide sequences but they still
occupy the same locus on the chromosome
Different alleles arise by the process of mutation
E.g. each allele might produce a different coat colour in mammals
One allele might code for a black coat while the alternative allele might code for a
chestnut coat
When writing about genes it is conventional to use a single letter to represent a gene, while
different alleles may be indicated by using upper and lower case letters, e.g. A and a
Homozygous & heterozygous
Every individual has two copies of each allele; one on each chromosome in a homologous
pair
A homologous pair of chromosomes is a pair of chromosomes that match in size and
shape, and that contain the same genes at the same loci
The chromosomes may not contain the same alleles of each gene
One member of a homologous pair of chromosomes comes from one parent, while
the other comes from the other parent
When an individual has two identical alleles at a locus they are said to be homozygous, or
a homozygote
Homo = the same
When an individual has two different alleles at a locus they are said to be heterozygous, or
a heterozygote
Hetero = different

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YOUR NOTES


Chromosomes match up to form homologous pairs which have the same genes at the same
loci. While the genes are the same, the alleles may be different, meaning that individuals can
be either homozygous or heterozygous at a particular locus
Genotype & phenotype
The genotype of an organism refers to the alleles of a gene possessed by that individual
E.g. An organism's genotype could be represented by the letters gg
The genotype of an individual affects their phenotype; a phenotype is the observable
characteristics of an organism
E.g. every horse has two copies of a gene for coat colour in all of their cells, one on each
homologous pair of chromosomes; the gene could be notated using the letters A and a
A horse that has two A alleles has the genotype AA and is homozygous
If the A allele codes for a black coat, then the phenotype of the horse would be
black
A horse that has two a alleles has the genotype aa and is also homozygous
If the a allele codes for a chestnut coat then the phenotype of the horse would be
chestnut
Dominant & recessive
Not all alleles affect the phenotype in the same way
Some alleles are dominant; they are always expressed in the phenotype no matter which
other allele is present
This means they are expressed in both heterozygous and homozygous individuals, e.g.
A horse with the genotype AA would be said to be homozygous dominant and
would have a black coat phenotype
A horse with the genotype Aa would be said to be heterozygous and would still
have a black coat phenotype, as the allele for black coat colour is dominant over
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the lower case allele YOUR NOTES

It is possible to refer to a heterozygous individual as a carrier of the recessive 
allele; the allele doesn't show in the phenotype but could still be passed on to
offspring
Others are recessive; they are only expressed in the phenotype if no dominant allele is
present
This means that it is only expressed when present in a homozygous individual, e.g.
A horse with the genotype aa would be said to be homozygous recessive and
would have a chestnut coat phenotype due to the absence of the dominant black
allele
Codominance
Sometimes both alleles can be expressed in the phenotype at the same time; this is
known as codominance
When an individual is heterozygous they will express both alleles in their phenotype
When writing the genotype for codominance the gene is represented by a capital letter
and the alleles are represented by different superscript letters, for example IA
An example of codominance can be seen in coat colour in cattle
The gene for coat colour can be represented by the capital letter C
The alleles for coat colour can be represented by letters R (red) and W (white)
A cow that is homozygous and has a red coat has the genotype CRCR
A cow that is homozygous and has a white coat has the genotype CWCW
A cow that is heterozygous will have a roan coat, containing a mixture of red and
white hairs; the genotype will be CRCW

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Genetic Pedigree Diagrams YOUR NOTES

Family pedigree diagrams can be used to trace the pattern of inheritance of a specific 
trait, e.g. a genetic disorder, through generations of a family
Pedigree diagrams can provide information such as
Whether a trait is caused by a dominant or recessive allele
Whether a trait is more likely to be inherited by males or females
The genotypes of individuals in the family
The probability that an individual in the family will inherit a trait

Pedigree diagrams can be used to show the pattern of inheritance of a genetic trait
Males are indicated by the square shape and females are represented by circles
Affected and unaffected individuals can be indicated using colour, shading, or cross-
hatching
Horizontal lines between males and females show that they have produced children
Vertical lines show the relationship between parent and child
Roman numerals may be used to indicate generations
For each generation the eldest child is on the left and each individual is numbered
The family pedigree above shows the following
Both males and females are affected by the trait in question
Every generation has affected individuals
The eldest son in the second generation is affected
There is one family group that has no affected parents or children
The diagram above does not contain enough information to show
Whether the trait is caused by a dominant or recessive allele
The genotypes of the individuals involved

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YOUR NOTES
 Worked Example

The pedigree diagram below traces the inheritance of albinism through several
generations. Albinism affects the production of the pigment melanin leading to
lighter hair, skin and eyes.

Using the pedigree chart, deduce and explain the following:

1. The type of allele that causes albinism
2. The genotype of individuals 9 and 7
3. The possible genotypes of 10 and 11

Question 1
Albinism is caused by a recessive allele
Person number 9 is an affected individual despite parents 6 and 7 being unaffected; 6 and 7
must both be carriers of the recessive allele and 9 has inherited one recessive allele from
each parent
Question 2
The genotype of person 9 must be homozygous recessive (aa) and the genotype of 7 must
be heterozygous (Aa)
Person 9 is an affected individual with albinism; as this is determined by the recessive allele
they must have two copies of the albinism allele
Person 7 must be heterozygous as he does not have albinism but has passed on the
recessive allele to person 9
Question 3
The possible genotypes of 10 and 11 are heterozygous (Aa) or homozygous dominant (AA)
They are both unaffected individuals so must possess at least one dominant allele (A),
however, it is possible that they each might have inherited a recessive allele (a) from one
parent (both parents must have a copy of the recessive allele in order for person 9 to have

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albinism) YOUR NOTES


 Exam Tip
When answering questions about pedigree charts for genetic diseases, it is always
useful to remember which phenotype is caused by the homozygous recessive
genotype. You can write these genotypes onto your chart and it will give you a good
starting point for working out the possible genotypes of the rest of the individuals in
the chart.

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Sex Linkage YOUR NOTES

Sex-linked genes are located on the sex chromosome 
This means the sex of an individual affects which alleles they pass on to their offspring
through their gametes
If the gene is on the X chromosome, males (XY), will only have one copy of the gene,
whereas females (XX) will have two
The X chromosome has many more genes on it than the Y chromosome, so sex-
linkage that involves the Y chromosome is very rare
Sex linkage is notated using a capital letter to represent the chromosome X or Y and a
superscript letter to represent the allele
There are three genotypes for females, e.g. for a genetic trait caused by a recessive allele
XAXA = unaffected
XAXa = carrier
XaXa = affected
Males have only two genotypes, e.g.
XAY = unaffected
XaY = affected
It is not possible for males to be carriers of X-linked traits, nor for them to pass such traits
on to their sons; males only pass Y chromosomes on to their sons

 Worked Example
Red-green colour blindness is a well known sex-linked trait in which individuals find
it difficult to distinguish between the colours red and green. It is controlled by is a
gene found on the X chromosome; the dominant B allele codes for normal vision
and the recessive b allele results in red-green colour blindness.
Use a genetic diagram to show how two parents with normal vision can have
offspring with red-green colour blindness.

Step 1: Work out the genotypes of the parents

Both parents have normal vision so each must have a copy of the dominant B allele
The father only has one copy of the X chromosome, so his genotype must be XBY
The question tells us that the parents must be able to have a child with colour blindness, so
this allele must come from the mother; she must therefore have a copy of the b allele and
her genotype must be XBXb
Step 2: Work out which gametes the parents can produce
The genotype XBY will produce gametes containing either XB or Y
The genotype XBXb will produce gametes containing either XB or Xb
Step 3: Use the gametes to complete a Punnett square and then indicate which
offspring will be affected

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XB Y YOUR NOTES
XB XBXB XBY 
Xb XB XbY
The individual with genotype XbY will be affected by red-green colour blindness; they only
have only copy of the X chromosome and it contains the colour blindness allele

 Exam Tip
Note that in the worked example above the letter B has been chosen to represent
colour blindness rather than the letter C. It can often be a good idea to choose
letters for which there is a clear difference between the upper and lower case; this
avoids losing marks in exams because examiners can't tell the difference between,
e.g. C and c, or S and s

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2.16 Cystic Fibrosis YOUR NOTES


Cystic Fibrosis
Genes can affect the phenotype of an organism
A gene codes for a single polypeptide
The polypeptide can affect the phenotype, e.g. it could form part of an enzyme or a
membrane transport protein
Genetic disorders are often caused by a mutation in a gene that results in a differently-
functioning or non-functioning protein that alters the phenotype of the individual
Cystic fibrosis
Cystic fibrosis is a genetic disorder of cell membranes caused by a recessive allele of the
CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene located on
chromosome 7
This gene codes for the production of chloride ion channels required for secretion of
sweat, mucus and digestive juices
A mutation in the CFTR gene leads to production of non-functional chloride channels
This reduces the movement of water by osmosis into the secretions
The result is that the body produces large amounts of thick, sticky mucus in the air
passages, the digestive tract and the reproductive system
Because cystic fibrosis is determined by a recessive allele, this means
People who are heterozygous won’t be affected by the disorder but are carriers
People must be homozygous recessive in order to have the disorder
If both parents are carriers the chance of them producing a child with cystic fibrosis is
1 in 4, or 25 %
If only one of the parents is a carrier with the other parent being homozygous
dominant, there is no chance of producing a child with cystic fibrosis, as the recessive
allele will always be masked by the dominant allele

Cystic fibrosis is a genetic disorder caused by a recessive allele

The respiratory system
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Mucus in the respiratory system is a necessary part of keeping the lungs healthy YOUR NOTES
It prevents infection by trapping microorganisms 
This mucus is moved out of the respiratory tract by cilia
In people with cystic fibrosis, due to the faulty chloride ion channels, the cilia are unable to
move as the mucus is so thick and sticky
This means microorganisms are not efficiently removed from the lungs and lung infections
occur more frequently
Mucus builds up in the lungs and can block airways which limits gas exchange
The surface area for gas exchange is reduced which can cause breathing difficulties
Physiotherapy can support people with cystic fibrosis to loosen the mucus in the airways
and improve gas exchange
The digestive system
Thick mucus in the digestive system can cause issues because
The tube to the pancreas can become blocked, preventing digestive enzymes from
entering the small intestine
Digestion of some food may be reduced and therefore key nutrients may not be
made available for absorption
The mucus can cause cysts to grow in the pancreas which inhibit the production of
enzymes, further reducing digestion of key nutrients
The lining of the intestines is also coated in thick mucus, inhibiting the absorption of
nutrients into the blood
The reproductive system
Mucus is normally secreted in the reproductive system to prevent infection and regulate
the progress of sperm through the reproductive tract after sexual intercourse
The mucus in people with cystic fibrosis can cause issues in both men and women
In men the tubes of the testes can become blocked, preventing sperm from reaching
the penis
In women thickened cervical mucus can prevent sperm reaching the oviduct to fertilise
an egg

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2.17 Genetic Screening YOUR NOTES


Uses of Genetic Screening
Some circumstances, e.g. in a pregnancy where there is a family history of a genetic
disorder, may require individuals to determine if they have a particular allele present in their
genome
This can be determined by genetic screening
There are three main uses of genetic screening
Identifying individuals who carry an allele at a gene locus for a particular disorder
The screening of embryos prior to implantation during fertility treatment; this is
Preimplantation Genetic Diagnosis (PGD)
Testing a foetus before birth; this is prenatal testing
Identification of carriers
Carrier testing is offered to individuals with a history of genetic disorders in their family
It can show whether people who have no symptoms carry the allele for particular
disorders, such as cystic fibrosis
Cell samples can be extracted from, e.g. blood or saliva, before being tested for the
presence of specific alleles
Couples can be tested prior to having children to determine the probability of future
children inheriting the disorder
Some of the benefits of carrying out genetic screening at this stage include
Families can make informed decisions before having children
Women can decide whether to have prenatal testing during pregnancy
Preimplantation Genetic Diagnosis (PGD)
IVF, or in vitro fertilisation is a type of fertility treatment during which fertilisation is carried
out in the lab; embryos produced in this way can be implanted into the uterus where they
develop into a foetus
Sometimes a couple might choose to have a child by IVF if they know that they are at
increased risk of certain genetic disorders, as it allows them to screen any embryos
produced using PGD
PGD involves analysis of the DNA of an embryo prior to implanting it into the uterus
The sample of DNA to be analysed can be obtained by taking cell samples
from embryos produced during IVF
Benefits of PGD include
Evidence suggests that the process does not harm the embryo in any way
Reduces the chances of having a baby with a genetic disorder
It avoids abortion as it is carried out before implantation of the embryo
It is worth noting that some people believe that an embryo is as worthy of human
status as a foetus or a baby, so the discarding of affected embryos after PGD is
not ethically straightforward for everyone
Prenatal testing
Prenatal testing is offered to pregnant women with a family history of genetic disorders

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It involves testing the foetus for genetic diseases during the course of a pregnancy YOUR NOTES
The DNA can be obtained by chorionic villus sampling or amniocentesis in the uterus 
Chorionic villus sampling
This involves removing and testing a small sample of cells from the placenta using a
fine needle
The cells contain foetal DNA which can be analysed for genetic disorders, allowing
parents to make informed decisions about the pregnancy and foetus
Advantages of this process include
It is carried out at around 11-14 weeks of pregnancy, so any problems can be
picked up early on
A relatively large tissue sample can be collected, providing plenty of cells to
analyse
Results are available rapidly
Potential implications of chorionic villus sampling that should be considered include
The process has a 1-2 % risk of miscarriage
The process cannot pick up any disorders that are caused by alleles of genes
located on the paternal X chromosome, as this chromosome is inactive in the
placental cells sampled
Amniocentesis
This involves removing and testing a small sample of cells from amniotic fluid using a
fine needle
The amniotic fluid is the fluid that surrounds the foetus within the uterus
The fluid contains foetal cells which contain DNA to be analysed
Potential implications of amniocentesis that should be considered include
It is carried out at around 15-20 weeks of pregnancy; this is relatively late in the
pregnancy, making decisions about abortion more difficult for some parents
The procedure has a 1 % risk of miscarriage
It takes 2-3 weeks for results to be available
Benefits of prenatal testing include
The tests allow parents to make informed decisions about the progress of a
pregnancy
Results can help parents prepare for the future care of the child, including medical
treatment

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Implications of Prenatal Genetic Screening YOUR NOTES

Prenatal genetic screening involves analysis of the DNA of a foetus taken from the uterus 
during pregnancy
Examples of prenatal screening methods include chorionic villus sampling and
amniocentesis
Both forms of prenatal screening come with associated risks and potential ethical
dilemmas, so it is important that parents considering this type of screening have thought
about the implications
Positive implications
Prenatal screening can provide advance notice of the birth of a child with a
genetic disorder, giving time for parents to be educated and to make decisions
about medical treatments
The risk of harm to the foetus during prenatal screening are low; around 1-2 % for
both methods
Some parents may feel able to make the decision to end a pregnancy on
discovering that a foetus has a life-limiting or potentially fatal diagnosis
Some parents may choose to continue with a pregnancy after receiving a fatal
diagnosis, but they have time to process the results and grieve before the birth of
a child who may not survive for long outside the uterus
Genetic counsellors are available to help parents think through the results of
prenatal testing
Negative implications
Both methods of prenatal screening bring a small risk of miscarriage
Amniocentesis provides results relatively late in pregnancy, making decisions
about termination of a pregnancy very difficult for some parents
Prenatal screening is not 100 % accurate
False positive results may lead to the termination of a healthy pregnancy
False negative results may give false expectations for the health of a foetus
Parents may experience pressure from society or their medical team to abort a
foetus with a genetic disorder
Some parents may believe that a foetus has human status even very early on
during a pregnancy, meaning that they would not consider abortion to be an
option even after early testing

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2.18 Ethical & Social Issues of Genetic Screening YOUR NOTES


Ethical & Social Issues of Genetic Screening
Some circumstances, e.g. in a pregnancy where there is a family history of a genetic
disorder, may require individuals to determine if they have a particular allele present in their
genome; this can be determined by genetic screening
As genetic screening can leave future parents with many questions, genetic
counsellors are available to help
Counsellors can be seen before screening has occurred; they may discuss the
following with the prospective parents
The probability of the couple having a child with a genetic disorder
Termination of the pregnancy
Therapeutic treatments possible for the child
Financial implications of having the child
Effect on existing siblings
Ethical issues
After screening the counsellors will read the results and explain them to the future
parents
Each use of genetic screening brings potential concerns that should be considered; these
concerns will differ depending on someone's religious, moral, and social position, e.g.
Belief that God is in control may mean that a pregnancy will be continued no matter
what genetic screening might show
Belief that embryos are potential human beings from conception would mean that
the discarding of embryos after embryo screening or the abortion of a foetus at any
stage would be considered impossible
Belief that abortion is only acceptable up to a certain stage of pregnancy may mean
that screening techniques that are carried out later in pregnancy can't lead to
termination
Some may feel that it is unethical to bring a child into the world who will struggle with
health issues, or who they will be unable to care for properly; this may mean that
abortion is considered to be the most ethical option
Processes that involve screening embryos could allow for embryos to be selected on
the basis of factors other than genetic health, e.g. sex or intelligence; many are
concerned about the potential future of 'designer babies'
Some cultures may have different traditions around genetic disorders, e.g. with
abortion considered to be more acceptable by some cultures than others
Positive screening results for non life-threatening conditions, e.g. Down syndrome,
can lead to the abortion of foetuses that could have gone on to live full and happy
lives; some feel that such conditions are being eradicated from society
An embryo or unborn baby has no ability to give consent or make decisions about its
future; some believe that they are deserving of full human rights while others do not

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Exam Tip YOUR NOTES

 Make sure that you are able to give a balance of arguments from different ethical

viewpoints; you may have personal views on some the issues covered, but you
should avoid sticking to only one side of any argument.

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