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NOTES
MUTATION
A mutation is a change in the structure or amount of an organism’s genetic material.
Mutations are normally RARE, SPONTANEOUS and RANDOM and most are harmful or lethal.
Most mutant alleles are recessive, and so are rarely expressed in the phenotype i.e. only when homozygous or when sexlinked.
External influences may change the rate of mutation.
MUTAGENIC AGENTS
These can artificially increase the rate of mutation – called induced mutation.
They include:
• Chemicals e.g. mustard gas
• Radiation e.g. gamma rays, X-rays, UV light
TYPES OF MUTATION
Gene mutation: a change in the structure of DNA in a gene.
Chromosome mutation: a change in the number or structure of chromosomes.
GENE MUTATIONS
Gene mutations are changes in the type, order or number of nucleotides within a gene, causing an
alteration in the resulting protein.
Altered proteins are often non-functioning e.g. an enzyme that will no longer fit its product.
Two main classes of gene mutation:
POINT MUTATION: a change in one of the base pairs in the DNA sequence of a single gene or
regulatory DNA sequence.
SPLICE-SITE MUTATION: a change in one or more nucleotides at an intron removal site.
GENE MUTATIONS: POINT MUTATIONS
● Substitution ● Insertion
● Deletion
Substitution mutations:
replacement of one nucleotide with another.
The effects of substitution are usually minor, with little or no
effect on the organism (silent or neutral mutations).
Substitution will have a more serious effect if the ‘new’ amino
acid is in a critical position in the protein (missense mutation).
EXAMPLE: Sickle cell anaemia
Sickle-cell anaemia results from the formation of an abnormal
form of haemoglobin due to a substitution mutation.
The sickled cells contain haemoglobin S which is less efficient
at carrying oxygen than normal haemoglobin.
Incorrect amino acid
The most serious substitution stops protein synthesis by
coding for a stop codon (nonsense mutation).
.
Missense mutation
Nonsense mutation
SUMMAR
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Summary: possible effects of substitution
Mutation type
Effect on amino acid produced
Effect on protein
Silent
Neutral
Missense
Nonsense
Same amino acid
Similar amino acid
Different amino acid
Stop codon produced
Same protein made
Same protein made
Different protein made
Halts protein synthesis
NOTES
Insertion and Deletion mutations
Insertion and deletion mutations lead to a major change in the gene: all codons after the mutation are altered and the
protein produced is not usually functional. They are known as FRAMESHIFT mutations.
GENE MUTATIONS: SPLICE-SITE MUTATIONS
Splice-site mutation:
substitution, insertion or deletion of one or more
nucleotides at a splice site on a primary mRNA
transcript.
This may prevent splicing and leave one or more
introns in the mRNA, which may lead to a
dysfunctional protein.
EXAMPLE
Mutations that cause the incorrect splicing of βglobin mRNA are responsible for some cases of βthalassemia, a disorder caused by the weakening
and destruction of red blood cells.
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CHROMOSOME MUTATIONS
NOTES
These involve a change in the number or structure of chromosomes. These mutations occur during meiosis (cell division
to produce gametes) and result from a failure in normal crossing-over.
[See Higher Bitesize (old H) for summary of meiosis.]
CHROMOSOME STRUCTURE MUTATIONS
Involve the breakage of one or more chromosomes and a change in number or sequence of genes.
Four types:
● DELETION
● DUPLICATION
● TRANSLOCATION
●INVERSION
DELETION
Chromosome breaks in two places and section becomes
detached. Two ends attach to give a shorter chromosome.
Effects of deletion
Effects are usually drastic as genes have been lost.
Example
Cri du chat syndrome is due to a deletion of a portion of
chromosome 5.
Individuals have severe mental difficulties and a small
head with widely-spaced eyes. The infant’s cry sounds like
a cat.
DUPLICATION
Section from homologous partner is inserted/attached,
leading to repetition of genes.
Effects of duplication
 Can happen without harming the individual
because there is still one good copy of the gene.
 May be a source of variation for species as the
‘extra’ gene may undergo beneficial point
mutation.
 Sometimes detrimental e.g. duplication of
oncogenes causes cancer.
INVERSION
Chromosome breaks in two places and the middle piece
turns round so that the normal gene sequence in that
part is reversed.
Effects of inversion
Usually leads to homologous chromosomes forming
complicated loops during crossing-over: genetic material
is lost, often giving rise to non-viable gametes.
TRANSLOCATION
Section from non-homologous chromosome is attached.
Translocation may be non-reciprocal (diagram) or
reciprocal (when two chromosomes swap pieces).
Effects of translocation
Leads to problems with pairing at meiosis; any gametes
usually not viable.
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NOTES
CHROMOSOME NUMBER MUTATIONS
Caused by non-disjunction - when a spindle fibre
fails to separate a homologous pair of
chromosomes during meiosis.
Non-disjunction during Meiosis I leads to two of
the gametes receiving an extra chromosome and
two gametes lacking that chromosome.
The frequency of nondisjunction is quite high in
humans but usually results in miscarriage very
early in pregnancy. If the individual survives,
he/she usually has a set of symptoms - a syndrome
- caused by the abnormal dose of each gene
product from that chromosome.
Example
Down (Down’s) syndrome is caused by nondisjunction of chromosome 21, leading to an
embryo having three of chromosome 21 (trisomy
21) rather than a pair.
COMPLETE NON-DISJUNCTION
Complete failure of spindle fibres leads to the formation of one diploid gamete (and
one with no chromosomes).
This often occurs in plants, leading to POLYPLOIDY – possession of extra sets of
chromosomes.
Examples of polyploid plant species: corn, wheat (hexaploid), cotton, sugar cane,
apple, swede, banana (triploid), potato (tetraploid), strawberry.
Polyploidy – causes
Polyploidy can occur naturally when errors during cell division create cells with
more than one set of chromosomes.
Polyploidy can be induced using chemicals that increase the chance of errors in cell
division.
Polyploidy - results
Polyploid plants are often larger and give higher yields.
Polyploid hybrids from more than one species often grow more vigorously and have
increased disease resistance.
Polyploid plants are fertile if even number of chromosome sets present e.g. 4n, 6n,
8n. Polyploid plants with uneven number of sets (3n, 5n etc.) are sterile and
therefore seedless. Plants can be propagated by asexual reproduction therefore
seedless plants can be grown e.g. bananas (triploid).
Gametes are haploid (1 set of
chromosomes); normal body cells are
diploid (2 sets).
Triploid and tetraploid chromosome sets
are examples of polyploidy.
Polyploidy in animals
Polyploidy is rare in animals as they cannot
cope with increase in body size and many
cannot reproduce asexually.
It occurs in some ‘simple’ animals and in
some fish e.g. salmon (tetraploid).
Polyploidy: role in evolution
Polyploidy is thought to have played an important role in the evolution of plants. Around 50% of plant species are
polyploid and it is likely that following the duplication of an entire genome plant species are able to evolve quickly.
Polyploid organisms may have an evolutionary advantage over diploid organisms:
• extra sets of chromosomes have the ability to mask any conditions caused by recessive alleles;
• duplicated chromosomes are free to accumulate mutations that may eventually result in a new beneficial trait.
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EVOLUTIONARY IMPORTANCE OF MUTATION IN HUMANS
NOTES
Examples: sickle-cell trait; lactose tolerance
SICKLE-CELL TRAIT
Sickle-cell anaemia is caused by a gene mutation, leading to the
production of haemoglobin S rather than normal haemoglobin
(allele H). Sickle-shaped red blood cells stick together, causing
problems with circulation and leading to anaemia, organ damage
and death.
DNA Point Mutation causing condition
Genotype HH: person with normal haemoglobin.
Genotype SS: person with sickle cell anaemia.
Genotype HS: person with sickle cell trait.
[Alleles H and S are co-dominant so S is partially expressed – blood
cells normal, slight anaemia.]
.
Sickle-cell trait and Malaria
Selective advantage of sickle-cell
trait
People with sickle cell trait are
resistant to malaria, so genotype HS
has a selective advantage in malarial
regions e.g. parts of Africa, leading
to a high percentage of HS in the
population (up to 40%).
Effect of the sickle cell haemoglobin gene on
survival in endemic malarial areas:
Distribution of malaria in southern
Europe, southwest Asia, and Africa.
Distribution of the sickle-cell allele
within the same area.
Death from
malaria
Death from sickle- cell
anaemia
LACTOSE TOLERANCE



Lactose is a sugar found in milk. It is a disaccharide, made up of the simple sugars glucose and galactose.
It is digested into these simple sugars by the enzyme lactase.
The gene coding for lactase is active in un-weaned babies but is switched off in adults in societies that do not eat
dairy products.
 Early human beings, before domestication of animals, were lactose-intolerant after weaning.
 At some point in human history, a random point mutation occurred that kept the lactase gene switched on.
 This gave people with that mutation a selective advantage as they could now digest lactose and so gain energy
from milk.
 This coincided with the domestication of animals, so people were able to drink milk for extra nutrition.
Lactose tolerance became common in societies that used a lot of dairy products (v. high in Northern Europe).
Some societies (e.g. China, Thailand) are mainly lactose-intolerant as they have not traditionally used dairy products.
Lactose-intolerant adults suffer adverse symptoms if they take milk e.g. cramps and nausea.
Lactose intolerance - global
Lactose intolerance – Europe
EVOLUTION
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EVOLUTION
NOTES
Evolution is the gradual change in the characteristics of a population of organisms over successive generations as a result
of variation in the population’s genome.
INHERITANCE
Genetic material can be inherited by:
1. Vertical transfer
2. Horizontal transfer
1. Vertical transfer of genetic material
Genes (sequences of protein-coding DNA) are transferred from parents down to their offspring.
This can happen by:
(a) Sexual reproduction
(b) Asexual reproduction
(a) Sexual reproduction
This involves two parents who differ from one another genetically. Offspring inherit different combinations of
genes from each parent.
(b) Asexual reproduction
- reproduction from a single parent. Produces offspring that are genetically identical to the parent.
2. Horizontal transfer of genetic material (prokaryotes)
Prokaryotes reproduce using asexual reproduction e.g. binary fission. They can also transfer genetic material from one
cell to another through horizontal gene transfer (HGT).
Horizontal gene transfer can occur in three ways:
(a) Transformation
When cells are destroyed, pieces of their
DNA remain and can be picked up by new
cells.
(b) Transduction – occasionally, when viruses
replicate, some host DNA is packaged up
with the virus. This then enters new cells
with the virus.
(c) Conjugation
A temporary connection called a
conjugation tube forms between
touching cells. Plasmid DNA is then
copied from one cell to another.
Rapid evolutionary change
It is thought that in early evolution of prokaryotes there was a lot of horizontal gene transfer (HGT) - obtaining a gene
from a neighbour is much faster than waiting for one to evolve. HGT is a risky strategy as the transferred genetic material
may not give an advantage.
Spread of antibiotic resistance
A significant amount of HGT still occurs in modern day prokaryotes. Resistance to antibiotics has occurred through the
transfer of plasmids carrying antibiotic resistance genes from one bacterium to another.
Horizontal transfer of genetic material (eukaryotes)
Although less common, horizontal gene transfer can occur in eukaryotes:
(a) From prokaryotes e.g. Agrobacterium tumefaciens is a bacterium that infects plant cells with a
plasmid that integrates into the genome of the plant.
(b) From viruses
Some viruses integrate their DNA into the host’s genome. The virus remains dormant (as a provirus) until it can
reproduce, when it then destroys the host cells e.g. Herpes virus, HIV.
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NOTES
NATURAL SELECTION
In 1858 Charles Darwin and Alfred Wallace presented a theory suggesting that the main driving force for evolutionary
change is natural selection.
 Organisms produce more offspring than the environment can support.
• All members of a species show variation from each other.
• A struggle for existence occurs and many offspring die before they can reproduce.
• Only those who are better adapted to the environment (the fittest) will survive and breed and pass those
adaptations on to their offspring.
• This process is repeated generation after generation causing gradual change in the characteristics of a species.
• Natural selection is a non-random process that results in the increase in frequency among a population of
individuals of those genetic sequences that confer an advantage on members of the population and aid their
survival.
Sexual selection
Sexual selection is a “special case” of natural selection – where selection is driven by the organism’s ability to get a mate.
It is the process of selection for traits that increase reproductive success.
Sexual selection operates by the following mechanisms:
1. Male to male competition
Males compete aggressively to defend territories and get access to females.
Larger, stronger males or males with better “weapons” win mating rights and pass those alleles on.
2. Female choice
Females select males which they consider high quality depending on the traits they display.
Selection of quantitative traits
Continuous variables, such as height, mass, skin colour, hair colour etc. are controlled by many genes – they are the
result of polygenic inheritance. Such characteristics are quantitative (e.g. mass, height) rather than qualitative (e.g.
colour).
When data for a continuous variable in a large
population is plotted, it produces a bell-shaped curve
- a normal distribution curve.
Directional selection
Common during period of environmental change.
Selection favours a version which was initially less
common causing a progressive shift in the mean
value e.g. European black bears increased in mass
during each ice age as larger bodies lose relatively
less heat than smaller ones.
Disruptive selection
Selection pressure selects extreme versions of a trait
at the expense of the intermediate versions. Occurs
when two different habitats/resource types become
available. Can result in the population being split into
two distinct groups.
Stabilising selection
Selection pressure goes against extreme variants and
favours the intermediate versions of a trait. Leads to a
reduction in genetic diversity e.g. human birth mass
remains within range of 3-4 kg. Babies with lower mass
are more susceptible to disease; those with higher mass
have difficulties during birth.
Disruptive selection
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SPECIATION (FORMATION OF NEW SPECIES)
NOTES
A group of living things belonging to the same species:
 have a similar anatomy and physiology;
 are reproductively isolated from other groups of living things;
 share a common chromosome complement and gene pool (gene pool - total of all genes in a population);
 interbreed to produce fertile offspring.
A species will remain unchanged if the environment is stable and the populations are able to freely exchange genes (they
have a common gene pool).
The formation of a new species is normally a very slow process and involves a number of stages.
There are two types of speciation: Allopatric speciation and Sympatric speciation.
ALLOPATRIC SPECIATION
Allopatric speciation occurs when gene flow between two (or more) populations is prevented by a geographical barrier
e.g. rivers, mountain ranges, desert, sea.
Outline of allopatric speciation
1. The original population is divided into two groups, separated by a geographical barrier.
2. Gene pools in each population gradually alter due to:




different mutations appearing in each sub-population giving rise to new variations in each group;
differences in local conditions (climate, disease or predators ) result in natural selection favouring different
alleles in each sub-population;
genetic drift - the change in the frequency of an allele in a population (small populations may not have full set of
alleles);
chance – catastrophe such as fire or flood.
3. Gene pools gradually alter over long period of time until groups become genetically isolated.
Groups can no longer exchange genetic information even if barrier is removed, resulting in new species.
X and Y can no longer
interbreed – new
species have formed
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SYMPATRIC SPECIATION
NOTES
Sympatric speciation: two (or more) populations live in close proximity in the same environment but still become
genetically isolated. This happens due to a behavioural or ecological barrier or by the occurrence of polyploidy (in plants
only). It is promoted by disruptive selection.






Outline of sympatric speciation
Large interbreeding population sharing the same ecological niche e.g. fruit flies living on hawthorn bushes.
Alternative ecological niche appears (e.g. species of apple tree introduced by humans)
Some members of the population start to exploit the new niche.
The two populations now exploit different resources (e.g. food source) and no longer interbreed.
Behaviour has become an isolating barrier.
Mutants better adapted to exploit the new resources appear (e.g. better camouflaged on apples) and
successfully breed.
Natural selection favours the new mutants and eventually, over a period of time, two genetically distinct species
are formed which can no longer interbreed.
HYBRID ZONES
An environment may contain several sub-populations of a
species, some of which – but not all – can interbreed.
Each sub-population can breed with its neighbour but may
not be able to breed with more distant members of the
species.
Hybrid zones: where interbreeding is possible; as a result
genes are able to flow between the sub-populations e.g. from
A to E via B, C and D.
A
B
C
D
E
Hybrid zones
If an intermediate population becomes extinct, gene flow is
disrupted and populations that are not neighbours become
genetically isolated therefore from two separate species.
A
C
D
E
SPECIATION ON SCOTTISH ISLANDS
Some species are ENDEMIC to Scottish islands i.e. they are found only here. Examples:
European wren (Troglodytes troglodytes): the subspecies on the Outer Hebrides is larger than on the mainland and wrens
on St. Kilda are larger still.
Long-tailed fieldmouse (Apodemus hebridensis): subspecies living on different Scottish islands vary in size and colour.
GENETIC DRIFT
The total of all the different genes in a population is called the gene pool. If a species is under no selective pressure,
frequencies of individual alleles will stay the same from generation to generation. Genetic drift is the random increase or
decrease in frequency of genetic sequences.
Genetic drift occurs due to: ● Sampling error
●Neutral mutations
● Founder effects
Sampling error: in a small population, not all alleles are passed onto the next generation and some may disappear
altogether. This reduces genetic variation and makes the population more uniform.
Neutral mutations: these change the nucleotide sequence of a gene, but do not change the amino acids coded for.
They are not subject to natural selection, but are affected by genetic drift.
Founder effects: if a population becomes isolated and is not large enough to contain the entire gene pool, gene
frequencies will be different in that population e.g. different blood group allele frequencies in different human
populations.
People
A
% population with blood group
B
AB
O
Chinese
31
28
7
34
Sioux Native
American
7
2
0
91
(North America was first populated by a small unrepresentative group of Asian people who migrated across a land bridge,
now the Bering Strait, and became separated.)
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GENOMICS and GENOMIC SEQUENCING
Genomics is the study of genomes. Genomics requires that the entire DNA of an organism is sequenced.
[The human genome of over 3 billion base pairs has now been sequenced.]
Major progress has been made possible by a fusion of molecular biology, statistical analysis and computer technology
called BIOINFORMATICS. Computers can be used for comparison of data within and between species, including looking
for start/stop or coding sequences and mutations.
GENOMIC SEQUENCING
Genomic sequencing is the process by which the sequence of nucleotide bases is determined for individual genes or even
entire genomes.
In order for the genome to be studied it must first be cut into more manageable sections. This is done by enzymes called
RESTRICTION ENDONUCLEASES.
A restriction endonuclease recognises specific short sequences (4-8 base pairs) of DNA nucleotides called RESTRICTION
SITES. Different endonucleases recognise different sequences. The enzymes will cut the DNA at every point where these
sequences appear.
Each DNA fragment is then sequenced to find out the order of its bases.
Sequencing DNA
A piece of DNA with unknown base sequence is selected and many copies are made.
Complementary DNA strands are made by adding DNA polymerase, primer, nucleotides and modified
nucleotides.
Modified nucleotides:
• are labelled with fluorescent dye, making them easy to identify;
• do not allow other nucleotides to bind to them, so halting replication at that point.
They are used to identify specific complementary nucleotides (1).
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NOTES
Once the sequence of each DNA fragment has been determined, the fragments have to be ‘put back
together’.
This is done by computer analysis of the fragments, looking for sections that overlap (2)
The fragment sequences are then arranged into one overall sequence using computer software (3).
This method of DNA sequencing is called shotgun sequencing.
1. The DNA sequence for each fragment of
DNA is worked out
2. The sequences are analysed and overlaps
are looked for.
3. The fragment sequences are arranged into
one overall sequence using computer
software.
.
The Human Genome Project
The Human Genome Project began in 1985 with the goal of determining the complete nucleotide
base sequence of the human genome. The project was completed in 2003 with the sequencing of the entire human
genome of around 3 billion base pairs (haploid).
Scientists all over the world collaborated on this project in the hope that a complete record of our genetic code would
lead to benefits to our health. This has already been the case for patients with cancers and genetic disorders.
GENOMICS
As well as sequencing the human genome, scientists have determined the genome sequence of a
range of other organisms:
• many pathogenic bacteria and viruses
• pest species e.g. mosquitoes
• model organisms (e.g. fruit flies, mice) that possess genes equivalent to those that cause diseases and disorders
in people.
Genomes and genes
The size of an organism’s genome is not directly related to the number of protein-coding genes it contains e.g. human
genome of around 3000 Mb has around 20 000 genes; pufferfish genome of around 400 Mb has around 30 200 genes.
[1 megabase (Mb) = 1 x 10⁶ bases]
COMPARATIVE GENOMICS
This involves comparing the genomes of:
• members of different species
• members of the same species
• cancerous and normal cells
to identify similarities or differences in the genomes, which could give clues to causes of disease etc.
Genome similarities
Comparison of many genomes has revealed that DNA sequences of important genes are highly similar (conserved) from
one organism to the next e.g. genes coding for proteins involved in aerobic respiration, or for key enzymes. The greater
the number of DNA sequences in common, the more closely related the organisms.
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NOTES
Genome differences
Genome variation affecting a single base pair is called a Single Nucleotide Polymorphism - SNP (‘snip’). A SNP results
from a substitution mutation. The millions of SNPs in the human genome have been mapped using
bioinformatics and are useful for research into disease.
PHYLOGENETICS
Phylogenetics is the study of evolutionary relatedness between groups of living things. Comparing the genetic sequences
of organisms can demonstrate their degree of relatedness: the more similar the genomes, the more related the
organisms are.
Phylogenetic trees
Over time a group of closely related living things will accumulate mutations e.g. nucleotide substitutions which gradually
alter the genome. The number of these differences per unit length of DNA between two genomes gives a measure of
how related two genomes are (evolutionary distance).
Phylogenetic tree based on differences between several genetic sequences of 5 related species
The further apart two species
are, the more distantly they are
related to each other (e.g. A
and D).
The closer they are the more
closely related they are (e.g. B
and C).
Species A
Species B
Common
Ancestor
Species C
Key:
One unit of genetic change
Species D
MOLECULAR CLOCKS
Nucleic acid molecules (and the proteins they code for) change over time as they are affected by mutations.
Mutations accumulate at a steady rate over time. Therefore the number of nucleotide substitutions that a genome
accumulates is regarded as being proportional to time.
By comparing this data with fossil records, the molecular clock gives information about:
• how long ago the most recent common ancestor of the species existed;
• the sequence in which the species evolved.
The use of molecular clocks can provide evolutionary insight but they have limitations, particularly as one
goes back in time.
α-globin as a molecular clock
The fewer the amino acid differences
between α-globin molecules, the closer the
relationship between the species.
Each point is for a pair/group of species.
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NOTES
THE THREE DOMAINS OF LIFE
Ribosomal RNA (rRNA) nucleotide sequences have been studied because they are shared by all living things.
Comparison of these sequences has demonstrated that living things belong to one of three domains:
• Bacteria (prokaryotes)
• Archaea (‘extreme’ prokaryotes)
• Eukaryotes (fungi, plants, animals)
EVOLUTIONARY TIMELINE
Timeline based on comparison of genome sequence data and fossil data:
Millions of years ago
4500-3500
Life on Earth
3900-2500
Cells similar to prokaryotes
3500
Last universal ancestor
2700
Prokaryotes able to photosynthesise
1850
Eukaryotes
1200
Multicellular organisms
580-500
Animals
485
Vertebrates
435
Land plants
PERSONAL GENOMICS
Sequencing the human genome took 13 years and cost millions of pounds; however, it now possible to
sequence a human genome in a day for a few hundred pounds.
This opens up many possibilities in medicine e.g.
• Predictive medicine
• Pharmacogenetics
Predictive medicine
Variations in DNA have been linked to many conditions e.g. cancer, heart disease, diabetes.
Once a person’s DNA sequence is known, the following could be investigated:
 Disease-causing mutations
 Mutations that increase the likelihood of developing a condition.
e.g. inherited mutation in BRCA1 & 2 genes increases risk of breast cancer (these genes usually produce
tumour-suppressor proteins).
Pharmacogenetics
How effective a drug is in any one person is affected by their DNA. Therefore, knowing the genome sequence could be
used to predict which medicines, and in which dosages, will be most effective in one person compared to another.
Causes of disease are often complex, with environmental factors playing a part so that knowledge of the genome alone
will not solve every problem.
Ethical issues
As a result of advances in this field, a question of ethics has arisen, including that of who should be able to access
personal genome information.
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NOTES
Examples
 Employers may not give a job to someone with risk of a disorder.
 Insurance companies and banks may decline services or increase premiums as a result of finding out about e.g. a
degenerative disease.
This has been termed genetic discrimination.
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