(a) The connection between DNA, genes, alleles,
chromosomes and the genome
The genome is the whole of the genetic material of an organism -
all of the DNA - coding and non-coding!
In animal and plant cells the genetic material (DNA) is contained in the
cell nucleus and arranged in 'packages' called chromosomes.
Chromosomes often occur in pairs e.g. human cells have 23 pairs of
chromosomes, 46 chromosomes in all.
Every chromosome is a very long strand of DNA that is coiled up to
give it a characteristic shape.
Reminders: DNA is a very long natural polymer in which the monomer
is a nucleotide that makes up the repeating unit in the molecular
chain. The DNA molecule consists of two strands wound and bound together to
form the double helix molecule.
For more on structure of DNA see
DNA and Protein Synthesis gcse
biology revision notes
A gene is a relatively short strand of DNA that forms a section of
a chromosome that codes for a specific protein.
Each gene has the coded instructions to tell a cell to combine a
particular sequence of amino acids to form a specific protein. In this case
the monomer unit is an amino acid and the resulting polymer is called a
protein.
Proteins control the development of an organism's characteristics and
all its functions.
As if this wasn't complicated enough, there is an extra layer of
complexity due to the existence of alleles!
Genes can exist in different versions called alleles - subtle
differences in the genetic DNA code.
Each allele produces a different form of the same characteristic
of an organism.
e.g. brown or blue eyes is a good example.
Each chromosome in a pair carries the same genes, BUT, they may
carry different alleles.
The diagram below sums up the relationship between all the terms
described and explained above.
Note: Genetic variants
Genetic variants (mutations) are caused by
alterations in the common nucleotide sequences in the DNA of genes.
The term variant can be used to describe an alteration that may be benign
(harmless), pathogenic (harmful), or of unknown significance.
The term
variant is increasingly being used in place of the term mutation.
Variants are key to successful evolution because genotype changes (usually
of the smaller type) can lead to changes in phenotype.
Human genetic
variation is
the genetic differences
both within and among populations. There may be multiple variants of
any given gene in
the human population.
A
mutation
may defined as
any change in a DNA compared to normal that results in a rare and abnormal variant.
For more on structure of DNA see
DNA and Protein Synthesis gcse
biology revision notes
For much more on mutations and variants see
Genetic
variation and mutations
and section on variation in
Evolution - theories and evidence, variation, speciation -
new/old species & extinctions
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(b) Genetic instructions and the
characteristics of an organism
The combination of all alleles for each gene of an
organism are called
genotypes.
It is the genotypes of each organism that makes it unique.
However, the characteristics shown by an organism are
called their
phenotypes.
The phenotype of an organism is primarily determined by the genotype, but
the phenotype can be influenced by the environment the organism is
interacting with.
e.g. under what conditions does an organism grow and develop?
The diet of an animal can affect how well it grows and how
healthy it is. A well nourished child grows strong and healthy. A
malnourished child short of protein, vitamins etc. may have stunted
growth, be too thin, physically weak and the immune system weakened
so the individual is more susceptible to infectious diseases.
A flower exposed to lots of sunlight, rich soil and adequate
water may grow a healthily rich green and have attractively coloured
flowers. If a plant is deprived of enough sunlight, nutrients or
water, it grows somewhat thinly and becomes limp, it tends to be
yellowish rather than green and petal colours may fade.
In both of the above cases, the genotype determines the maximum
healthy growth of organism, but this may be reduced by environmental
factors.
Therefore the variation of the phenotype is determined by a
combination of the genotype (genetic factors) and the conditions of growth
and development (environmental factors).
For more see
An introduction to genetic
variation and the formation and consequence of mutations
gcse biology notes
also
Introduction to the inheritance of characteristics and
genetic diagrams
gcse biology revision notes
and section on variation in
Evolution - theories and evidence, variation, speciation -
new/old species & extinctions
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(c) The
importance of genome knowledge - the human genome project
The genome is the term that describes the total
genetic material of an organism - all the DNA.
The human genome projects has mapped and
identified all the genes found in human DNA.
Every organism has its own unique genome
and scientists can now completely work it out - clever stuff!
Genome data is used to characterise species and
help research plant and animal evolution patterns.
See note 3. below on the human genome.
The human genome has around 3 billion base
pairs in the DNA sequences of the genes-chromosomes!
Apparently quite a lot of your DNA is 'junk',
but don't worry, and we won't go into that, just study hard, play
hard and enjoy life!
Thousands of scientists around the world have
collaborated on the human genome project.
We now know the complete human genome and over
20,000 to 25,000 genes have been located on it, but although
we know what many do (code for), there is much more to find out.
Around 1800 genes have been identified that
relate to human diseases - and this data is the target of medical
research to benefit medicine.
PLEASE NOTE that all humans share 99.9% of
their genomes, which makes you think!
How is our understanding of the human genome
helping science e.g. evolution theory or medicine?
Any new drug must be targeted
at some specific medical condition where there is a need.
The target might be blocking the
action of an enzyme or a gene with a chemical agent (drug) you can
interfere with the development of a disease e.g. the anti-cancer
drugs used in chemotherapy treatments to reduce the growth of tumour
cells or kill them.
Studies of the genomes and
resulting proteins in both plants and animals are proving useful to
identify 'targets'.
You then have to find a chemical
that will have an effect on the target, fortunately there are
databases of chemicals that have been previously screened for likely
effectiveness.
The screening might not initially
indicate the best molecule to 'hit the target' in a biochemical
sense, but, it may provide a starter molecule - which you can then
modify to make different derivative molecules, one of which might
provide a more effective treatment.
Medical applications
e.g. prediction and prevention of
disease, testing for and treating inherited diseases, more effective
medicines, BUT, there are ethical issues to deal with too.
1. It has been possible for genetic
scientists to identify particular genes (genetic variants) in the genome that are linked
to certain types of non-inherited diseases.
Hopefully it will lead to predicting
predisposition to certain diseases, leading to early
intervention with medical treatment and perhaps a preventing
disease actually developing.
If you know what genes predispose people
to certain diseases, medical advice can be more accurately given
e.g. choice of diet and other lifestyle factors based on the
results of genetic screening tests.
Many common diseases like cancer and heart
conditions are caused by the interaction of different genes, as
well as lifestyle factors.
See also
Introduction to genetic
variation - formation and consequence of mutations
and
Stem cells and uses
- leukaemia treatment
2. From the human genome project, by knowing the
genes associated with
an inherited disease
(genetic disorder), we can understand it more clearly and
then develop more effective treatments - which may involve
genetic engineering itself.
We know inheriting certain genes greatly
increase your risk of developing certain cancers, this can help
with making lifestyle choices to minimise the risk of suffering
from the disease - as with 1. above, its a sort of risk
management situation.
In the UK newborn babies are routinely
tested for particular genetic variants known to cause genetic
disorders e.g. the double recessive allele that causes cystic
fibrosis.
The results from genetic screening
enables the medical treatment-management to begin promptly
while the baby is still very young.
Children with leukaemia can have a genetic
test to help decide which is the most effective treatment in
terms of medication and its dose.
See further notes on
genetic screening of an
embryos or fetus (much more controversial)
and
Introduction to the inheritance of
characteristics and inherited disorders
It is hoped that all this new genetic
science will lead to the development of better, and more
personal, treatments for a wide range of medical conditions.
We are now developing drugs and other
techniques that work at the molecular level in combating
disease and tailored to suit the individual's body
chemistry.
The variations in patients genetic
variants (alleles) mean that one drug isn't necessarily as
effective with all patients suffering from the same
condition - so new drugs can be designed to suit these
'varying' patient situations.
3. We know certain alleles affect how
our body responds to certain diseases and their treatment.
Scientists hope to use this knowledge to
develop more effective drugs that can be specifically suited to
patients with certain alleles in their genome.
Different drugs can be tested, and their
effectiveness compared with the patient's alleles, and you can
compare existing drugs with new ones.
It has been found that some breast cancer
drugs are only effective in women if they have certain alleles
in their genome.
4. To help in these medical quests,
scientists are analysing the genomes of human pathogens to help us
understand and control certain infectious diseases.
The complete genome of bacteria such as
the deadly MRSA, which is resistant to antibiotics.
It is hoped that pathogen genome knowledge
will allow swifter decisions as to the best treatment
administered to patients i.e. determined by the genomics of the
specific bacterial strain.
The science of human evolution
and migration
The human genome project can be tackled by
various genetic strategies.
(i) Analysis of data from people's Y
chromosome inherited down the male line.
(ii) Analysing mitochondrial DNA inherited
through mothers.
Our knowledge of the human genome is
being used to trace the migration of certain populations
across the continents of the world.
The latest research suggests that all
modern humans have descended from a common ancestor who lived in
Africa, and their descendents have spread over all over the
Earth - moving by both land and sea.
This is known as the 'Out of Africa'
theory and seems to have begun around 60 000 years ago.
Why did this happen?
Maybe change in climate, so
seeking more food for hunter-gathering tribes?
It is known the climate in Africa
at this time became much dryer - less rain, less plant
life, less food for animals, less plants and animals for
humans to eat.
All humans have a very similar genome.
In terms of ancestors - genetically, who you were and
where you have been is 'hidden' in your genome! until, that is,
modern DNA analysis reveals all !!!
However, as different populations of
people migrated to different areas of the planet, small
differences in DNA 'evolved' (incorporated) into their
genome e.g. producing different skin or hair colour or
facial features.
The genetic variation is as little as
0.001%, but even so, genetic scientists can work out when
these new populations split off in a different 'genetic' and
geographical direction.
People who are related will have an
even more similar genome.
The human genome is being compared to some
of closest relative in the world e.g. primates.
Ever since researchers sequenced the chimp
genome in 2005, they have known that humans share about 99% of
our DNA with chimpanzees, making them our closest living
relatives - that should make you think!
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(d)
Genetic screening - using data from the
human genome project, potential medical treatments, issues
Introduction
When you know that a particular allele causes
an inherited genetic disorder you can take action e.g.
if an allele that causes an inherited disorder
is identified, we could have regular medical checks for
these specific diseases and get early diagnosis and subsequent
treatment.
Genetic treatment might be able to cure
the disease.
From the human genome project scientists can
identify the genes and alleles that may be responsible for causing
inherited disorders, and much faster prior to the mapping of the
complete human genome.
Common diseases like cancer and heart
conditions are caused by the interaction of our genes and our
lifestyle factors.
If we know which genes predispose an
individual to certain types of disease we could be given
personal advice on diet and lifestyle (in general) to minimise
the risk of suffering from particular diseases.
However, there are many issues to with genetic
testing results e.g.
(i) From the point of view of potential
parents, there maybe crucial choices regarding whether children
may be born with a genetically inherited disorder - especially
if both parents carried the same faulty allele.
(ii) Would insurance companies be allowed
to see your 'genetic profile', are they entitled to know it e.g.
as regards health or life insurance?
More on these points below in section
(d)
Examples of using genetic testing
Example 1. A couple wishing to start a
family might wish to know whether there is a risk of the
baby developing a genetic disorder. This another aspect of family
planning at the discretion of parents.
This can involve genetic testing at
various point e.g.
1. Prior to conception,
parents can be tested to see if they are carriers of a defective
gene known to cause a genetic disorder.
It may be known that one of the
parents comes from a family line where a genetic disorder
has occurred.
The parents may not suffer from the
genetic disorder, but they may be a carrier of the defective
gene.
The genetic tests would show if any
parent was a carrier and the probability of the baby
inheriting the disorder - the parents can then make an 'informed
decision' as to whether to have a child.
see
Introduction to the inheritance of
characteristics and inherited disorders
2. After conception or laboratory
fertilisation, the embryo or fetus (embryo >8 weeks
old) can be tested - see section (ii) below on embryonic genetic
testing.
A pregnant woman can be tested by
extracting a sample of DNA from the amniotic fluid
which surrounds the fetus in the womb - there is a very
small risk of causing a miscarriage.
The tests will show whether the
foetus's DNA is carrying any of the genetic variants linked
with a disorder.
If a positive test for such a variant
is found, the couple can then make an 'informed decision' as
to whether to terminate or continue with the pregnancy - a
very personal and agonising family planning decision.
3. The newborn baby can be
genetically tested to show whether a genetic disorder has been
inherited allowing early intervention of medical treatment and
subsequent long-term management of the disorder.
Example 2. Using
in vitro
fertilisation (IVF) embryos are fertilised in a
laboratory and then implanted into the mother's womb.
Prior to implantation it is possible to remove
a cell from an embryo and analyse the DNA i.e, the genes and likely genotypes/phenotypes.
This allows the detection of genetic disorders
e.g. cystic fibrosis (described above) which is caused by the
presence of one or more faulty genes.
You can choose to allow a genetic
disorder free embryo to fully develop into a baby in the
mother's womb - this minimises the baby inheriting the genetic
variants linked with the disorder.
However, this ability to analyse genes in this
way leads to ethical, social and economic concerns and questions
about embryonic testing i.e. embryo screening for abnormal-undesired
genetic traits, on which crucial decisions can be made e.g.
termination of pregnancy.
e.g. after screening, embryos produced by
IVF, containing abnormal alleles can be destroyed.
Example 3. Other points on genetic testing
Genome research data shows scientists the
common genetic variations between people, most of which are
benign and no danger to our health.
However, as I've already pointed out:
Some
genetic variations are linked to our predisposition to certain
disease - so this will help to design new drugs specifically
tailored to suit people of a particular genetic trait.
In the UK newborn babies are
routinely tested for particular genetic variants known to
cause genetic disorders e.g. the double recessive allele
that causes cystic fibrosis.
The results from genetic
screening enables the medical treatment-management
to begin promptly while the baby is still very young.
Arguments for embryonic/fetal screening and other
genetic testing
(i) It stops newborn babies suffering as they
grow up into adults.
(ii) Reducing the number of people suffering
with a genetic disorder that is costly for healthcare systems to
deal with.
(iii) Procedures like IVF, accompanied by
genetic testing, are strictly regulated and parents are not allowed
to choose desirable traits.
Parents are not allowed to choose the sex
of their child, unless it is for good medical health reasons.
(iv) Other 'positive' points on genetic
testing:
Early intervention for potentially serious
diseases has already been mentioned.
Drugs for chemotherapy in cancer treatment
are continually being developed and tested - you match a drugs
performance against a person's specific genetic profile - this
increases a 'working' database of treatment for future patients
- another positive outcome from such treatment research is the
minimising of side-effects which can quite drastic from
ant-cancer drugs.
Arguments against embryonic/fetal screening and
other genetic testing
Many objections centre around
the ethical issues of
IVF.
(i) IVF procedures often
result in unused embryos being destroyed and some people
consider this unethical - immoral, because you have destroyed a
potential human life.
Even using embryos in
research projects is considered to be unethical.
(ii) Terminations of IVF
pregnancies on the grounds the baby may be born with a genetic
disorder implies that the resulting children are undesirable and
prejudice increased towards them.
Would potential parents feel
under pressure NOT to have children with a potentially inherited
genetic disorder.
(iii) The genetics and genetic testing of
embryos before implantation in the mother's womb raises the
ethical issue of preferential choice of characteristics of the
baby e.g. choice of gender, eye colour irrespective of whether you allow
a child to be born with disabilities.
(iv) Genetic screening is
expensive and the costs of gene technology treatments are
high.
The cost increases, the more
personal the treatment, because the more specialised the drugs
must be.
Surely this risks unfair
access to these expensive treatments?
In the UK NHS treatment
is free - BUT, is it locally available? Can you jump the
queue by using private medicine?
In other countries, or UK
private medicine - what does your insurance premium cover?
(v) The accuracy of genetic
testing
Unfortunately, due to the
complexity of DNA structure, genetic testing is not 100%
accurate.
A positive test for a
faulty gene, that is incorrect, will causing stress to the
couple, and possibly the wrong decision to terminate a pregnancy
because of fear of the baby inheriting a genetic disorder
when there is actually no need to be concerned.
A negative test for a
faulty gene, that is incorrect, means the couple are
completely unprepared for the birth of a child with a
genetically inherited disorder, causing considerable stress in
their lives when the baby is born.
(vi) Other 'negative' points on
genetic testing:
Is the use of gene technology
good in the long term, since we don't actually know what the
effects will be on future generations?
What might you think if you
know from an early age you are more susceptible (more
predisposed) to a particular disease? Won't this lead to
stress thinking about it, especially if there isn't cure for
it? Might you feel uneasy and worried if you 'seem' to
exhibit symptoms?
Would you be discriminated
against by insurance companies (e.g. insurance refusal or
increased premiums) or employers (e.g. refused long-term job
contract) if they knew you were likely to suffer from a
genetically inherited disorder.
Society must decide on a
code of conduct relating to potential discrimination AND
privacy of your medical details.
Just imagine the
problems caused if you genetic profile had to be
submitted with a job application!
