3.8- Chapter 20- Gene Expression

Question 1

What is a mutation?

Answer 1

Any change to the base sequence of the DNA of an organism.

Question 2

What is a gene mutation?

Answer 2

• Any change to one or more nucleotide bases or any rearrangement of the bases.
• Might arise during DNA replication.

Question 3

What is the effect of a gene mutation?

Answer 3

• The order of DNA bases in a gene determines the sequence of amino acids in a polypeptide.
• If a mutation occurs, the alteration of the sequence of base sequence in DNA can change the result in a different sequence of amino acids- primary structure- in the encoded polypeptide, altering the tertiary structure of the protein it forms.
• You should be able to relate the nature of a gene mutation to its effect on the encoded polypeptide.
• May have to state the specific effect of a mutation- read the information in the question carefully to see what it effects- proteins, mitochondria etc.
• **If there is a change in the DNA sequence at any time, remember it is a mutation and specify the mutation- may be worded confusingly
  **

Question 4

What are the benefits and negatives of mutations?
Hint: 6 detailed points for negative

Answer 4

• Benefits- produce genetic diversity necessary for natural selection and speciation.
• Negatives:
• Almost always harmful and produce an organism less well suited to its environment.
• Mutations that occur in body cells rather than in gametes can lead to disruption of normal cellular activities- such as cell division leading to cancer.
• Polypeptides make proteins so a change in the amino acid sequence of a polypeptide could change the tertiary structure of the protein, so that it doesn’t work properly e.g. enzymes active sites could no longer be complementary to the substrate so they may be unable to catalyse reactions.
• Some mutations can increase the likelihood of developing certain cancers e.g. mutations of the gene BRCA1 can increase the chances of developing breast cancer.
• Some mutations can cause genetic disorders- inherited disorders caused by abnormal genes or chromosomes e.g. cystic fibrosis.
• If a gamete containing a mutation for a type of cancer or genetic disorder is fertilised, the mutation will be present in the new foetus formed.

Question 5

What is the difference between a hereditary and acquired mutation.

Answer 5

• Hereditary mutation are passed onto offspring.
• Acquired mutations- mutations that occur in individual cells after fertilisation- in adulthood.

Question 6

What are the two ways that gene mutations can alter the genetic code.

Answer 6

• Some gene mutations change only one triplet code.
• Frameshift mutations- change the number of bases in the DNA code.

Question 7

Why do not all single-base mutations affect the order of amino acids coded for in protiens?

Answer 7

• The degenerate genetic code means some amino acids are coded for by more than one DNA triplet, so not all types of mutation will always result in a change to the amino acid sequence- primary structure- of the polypeptide.
• Amino acids may be coded for by more than one codon- have the same codon
• Also, may affect introns which have no effect.
  replaces a bond-forming amino acid with an amino acid that forms the same bond (or no bond with no bond) then no effect.

Question 8

How do frameshift mutations affect the DNA?

Answer 8

• Change the number of bases in the DNA code.
• Change the nature of all base triplets downstream from the mutation- shifts them- code is read in a different way.
• Have a huge effect on the base sequence of a gene.
• Include additions, duplications and deletions.
• Almost always change the amino acid sequences of the polypeptide close to the end of a gene.

Question 9

What are the different types of gene mutation?

Answer 9

• Addition.
• Deletion.
• Substitution.
• Inversion.
• Duplication.
• Translocation of bases.

Question 10

What is a substitution of bases mutation?

Answer 10

A base in a section of a DNA molecule is replaced by another nucleotide that has a different base.

Question 11

What is the impact of a single base substitution on the structure of a polypeptide?

Answer 11

• Change in sequence of amino acids- primary structure.
• Change in hydrogen/ ionic/ disulfide bonds.
• Alters tertiary structure.

Question 12

How is a substitution of bases mutation often a simplifcation.

Answer 12

For simplicity the effect of a mutation caused by a change to a single base is often used as an example, in practice it is often more than one base involved.

Question 13

What are the three possible consequences when a base is substitution.

Answer 13

• Depends on which new base is substituted and where.
• Formation of a codon for a different amino acid- the sequence of the polypeptide produced would differ by one amino acid- different primary structure- changes hydrogen/ ionic/ disulfide bonds. The protein which the polypeptide is part of may differ in shape not function properly as the specific tertiary structure is altered e.g. Enzyme- active site may no longer be complementary to the substrate and won’t catalyse the reaction.
• Formation of a different codon but one that codes for the same amino acid as before- genetic code is degenerate so most amino acids have more than one codon- mutation has no effect on the polypeptide produced.
• Formation of one of three of the stop codons- mark the end of a polypeptide chain- production of the polypeptide coded for by the section of DNA is stopped prematurely. The final protein would be significantly different and the protein would not perform its normal function.

Question 14

Describe a deletion of bases mutation.

Answer 14

• Loss of a nucleotide base from a DNA sequence.
• Large impact on the phenotype.
• Creates a frame shift to the left- the reading frame that contains each three letters of the code has been shifted to the left by one letter.
• The gene is now read in the wrong three-base groups and he coded information is altered.
• Most triplets and the amino acids they code for will be different.
• Polypeptides will be different- leads to the production of a non-functional protein which could alter the phenotype.

Question 15

What is the significance of position in a deletion of bases mutation.

Answer 15

• One deleted base at the start of the sequence- could alter every triplet in the sequence.
• Deleted base at the end of the sequence- smaller impact but could still have consequences.
• If three consecutive bases are removed or any multiple of three bases- there won’t be a frame shift.

Question 16

Describe an addition of bases mutation.

Answer 16

• Extra base becomes inserted into the sequence.
• Similar effect to a base deletion.
• Frame shift to the right and the whole sequence of trippets become altered.
• If three consecutive extra bases are added or any multiple of three bases- there won’t be a frame shift.
• The resulting polypeptide will be different from the one produced form a non-mutant gene but not to the same extent as if there were a frame shift.

Question 17

What is a duplication of bases mutation.

Answer 17

One or more bases are repeated- frame shift to the right.

Question 18

What is an inversion of bases mutation?

Answer 18

• Group of bases become separated from the DNA sequence and rejoin at the same position but in reverse order.
• The base sequence is reversed and this affects the amino acid sequence.
• Doesn’t change the number of DNA bases.

Question 19

What is a translocation of bases mutation?

Answer 19

• A group of bases become separated from the DNA sequence and moves from one location in the genome to another.
• Movement can occur within the same chromosome or to a different chromosome.
• Often have significant effects on gene expression leading to an abnormal phenotypes.
• Effects include the development of certain forms and cancer and reduced fertility.

Question 20

How do mutations occur.

Answer 20

• Mutations arise spontaneously during DNA replication.
• Permanent changes in DNA and occur without any outside influence.
• Random occurrences but occur with predictable frequency- mutation rate.

Question 21

Describe how the natural mutation rate can vary.

Answer 21

• Natural mutation rate varies in different species but typically 1 mutation per 100,000 genes per generation.
• The basic mutation rate can be increased by mutagenic agents (mutagens).

Question 22

What are mutagenic agents?

Answer 22

Factors that increase the rate of gene mutation.

Question 23

What are some mutagenic agent examples

Answer 23

• High energy ionising radiation- alpha and beta particles, short wavelength radiation such as X-rays and ultra violet light. Disrupt the structure of DNA.
• Chemicals- such as nitrogen dioxide or Benzopyrene in tobacco smoke- may directly alter the structure of DNA or interfere with transcription.
• Viruses.

Question 24

How can mutagenic agents increase the rate of mutation.

Answer 24

• Acting as a base- chemicals called base analogs can substitute for a base during DNA replication echoing the base sequence in the new DNA e.g. 55-bromouracil can substitute for thymine and can pair with guanine instead of adenine, causing a substitution mutation in the new DNA.
• Altering bases- some chemicals can delete or alter bases:
• Chemicals can remove groups from nucleotide bases e.g. nitrous acid can remove a group from cytosine changing it into uracil.
• Other chemicals can add groups to nucleotides e.g. benzopyrene in tobacco smoke- adds a group to guanine to make it unable to pair with cytosine, when DNA polymerase reaches the guanine it inserts other bases.
• E.g. Alkylation agents can add an alkyl group to guanine, changing the structure so it pairs with thymine instead of cytosine.
• Changing the structure of DNA- some types of radiation can change the structure of DNA, causing problems during DNA replication:
• Ionising radiation- e.g. X-rays- produces reactive agents- alter the shape of bases in DNA so DNA polymerase can’t act on them.
• Ultraviolet radiation affects thymine in DNA- causes adjacent thymine bases to pair together- disrupting DNA replication.

Question 25

Why is it important to investigate mutagenic agents?

Answer 25

* Scientific research and experimentation has enabled the identification of dangerous mutagenic agents. The effects of mutagenetic agents are complex and the harm they can cause is debatable. * Commercial organisations with interests in for example tobacco have interests in research and may fund it to benefit their business, it is important that results of research are peer reviewed by other scientists from a variety of background. * Peer reviews are achieved by publishing research finding scientific journals with global readership. The conclusions and claims made can then be debated and tested with further experimentation, to then be accepted, modified or rejected depending on further research. * Scientific research helps decision-makers such as governments and heads of business to take appropriate action to benefit society- e.g. implementing regulations, while also balancing the risk with benefits to society e.g. X-rays being beneficial as a diagnostic tool.

Question 26

What is a stem cell?

Answer 26

* Undifferentiated and unspecialised cells that can divide to become new specialised cells. * All multicellular organisms have some form of stem cells. * In mature mammals, only stem cells retain the ability to differentiate into other cells.

Question 27

What are the sources of stem cells in mammals?

Answer 27

* Embryonic stem cells- come from embryos in early stages of development. Become the specialised cells needed to form a foetus. Can differentiate into any type of cell in the initial stages of development. * Umbilical cord blood stem cells- derived from umbilical cord blood and similar to adult stem cells. * Placental stem cells- in the placenta and develop into specific types of cells. * Adult stem cells: * Become specialised cells that need to be replaced in some adult tissues e.g. stem cells in the intestines constantly replaced intestinal epithelial cells. * Found in the body tissues of foetus through to adult. * Specific to a particular tissue or organ within which they produce the cells to retain and repair tissues throughout an organism’s life. * Stem cells that occur in adult animal tissues need to be constantly replaced. * Stem cells have the ability to divide to form an identical copy of themselves in self-renewal.

Question 28

What are the different types of stem cell (in order of specialisation)?

Answer 28

1. Totipotent. 1. Pluripotent. 1. Multipotent. 1. Unipotent.

Question 29

What are totipotent stem cells.

Answer 29

* Can differentiate into any type of body cell. * Found in the zygote, and first few cell divisions of an embryo. * Totipotent cells occur only for a limited time in early mammalian embryos.

Question 30

What are pluripotent stem cells?

Answer 30

* Can differentiate into almost any type of cell apart from the placenta. * Found in embryo.

Question 31

What are multipotent cells?

Answer 31

* Can divide to form a limited number of specialised cell types. * Usually develop into cells of a particular type. * Found in adult stem cells of mature mammals e.g. bone marrow stem cells produce any type of blood cells.

Question 32

What are unipotent stem cells.

Answer 32

* Only differentiate into a single type of cell. * Derived from multipotent stem cells and found in mature mammals. * E.g. Cardiomyocytes- heart muscle cells that can divide to produce new heart tissue and repair damage to heart muscles.

Question 33

Describe producing tissue cultures of explants of cauliflower. | (Not a required practical).

Answer 33

* Explants are small pieces of a plant which are grown into a clone of the original plant. * Clones of cauliflower tissue can be used to demonstrate its totipotency. * Cauliflower- comprised mostly of actively dividing cells. * o The explant is grown in an agar growth medium after being sterilised to ensure that no fungi contaminate the experiment, causing fungal growth rather than explant growth. The growth medium contains all the nutrient s needed for growth and sterilant to ensure no contamination occurs. The container is left by the sun/ light. * The experiment will grow a cauliflower clone from the explant, showing that cells in the explant have the capability to produce all the different cell types that make up a full cauliflower plant- totipotent.

Question 34

Why are single- celled organisms less efficient.

Answer 34

* Perform all essential life functions inside a single cell. * They perform all functions adequately but can’t be efficient because each function requires a different type of cellular structure, enzymes and other proteins. * One activity may be suited to a thin cell while another might suit a spherical cell. * No cell can provide the best conditions for all functions.

Question 35

How are multicellular organisms more efficient?

Answer 35

* Cells are specialised to perform specific functions. * Multicellular organisms are made up of many different types of specialised cells which are adapted in different ways to perform a particular role. * All the cells in a multicellular organism are derived from the mitotic divisions of a single fertilised egg- zygote. * In early development, an organism is made up of a tiny ball of identical cells- embryo. * As it matures, each cell takes on its own individual characteristics and adapts to the function it will perform when it is mature- becomes specialised.

Question 36

Describe cell speciliasation.

Answer 36

* Cells are able to control their metabolic activities by regulating the transcription and translation of their genome. * Although the cells within an organism carry the same coded genetic information, they translate only part of it. * In multicellular organisms, this control of translation enables cells to have specialised functions, forming tissues and organs. * Specialisation is irreversible in most animal cells- once cells have matured and specialised, they can no longer develop into other cells. * Specialised cells are developed from stem cells. Most of a cell’s DNA is not translated as the cell becomes specialised.

Question 37

How do plant cells specialise.

Answer 37

* Mature plants have many totipotent cells- in roots and shoots. * There are many factors that influence the growth of plant tissue cultures from totipotent cells- including plant growth factors- chemicals involved in growth and development of plant tissues.

Question 38

How do plant growth factors affect cell specialisation.

Answer 38

* Wide range of effects on plant tissues. * Effects on a particular tissue depend on the concentration of growth factor. * The same concentration affects different tissues in different ways. * The effect of one growth factor may be modified by the presence of another.

Question 39

How are totipotent cells specialised?

Answer 39

* Organisms- develop from a single fertilised egg. * Fertilised eggs have the ability to give rise to all types of cells. * Totipotent cells- cells which can divide and produce any type of body cell e.g. fertilised eggs, and early cells that are derived from the fertilised eggs. * During development, totipotent cells translate only part of their DNA, resulting in cell specialisation.

Question 40

What is cell differentiation?

Answer 40

Process where each cell develops into a specialised structure suited to the role it will carry out.

Question 41

Describe how cell differentiation works.

Answer 41

* All cells carry the same genes, and every cell is therefore capable of making everything that the body can produce. * Although cells contain all genes, only certain genes are expressed (transcribed and translated) or switched on- in each cell at different times, as each cell has a different structure dn function. * Differentiation results from differential gene expression. * Some genes are permanently expressed in all cells- genes that code for essential proteins involved in respiration, transcription, translation, membrane synthesis, ribosomes and tRNA synthesis are expressed on all cells. * Some genes are permanently not expressed (switched off) in some cells e.g. the gene for insulin in cells lining the small intestine. * Further genes are switched on and off when they are needed. * Genes being switched on or off is controlled by various processes explored later.

Question 42

What is the importance of proteins in cell differentiation.

Answer 42

* Differentiated cells differ from each other visibly as they produce different proteins. * Proteins that a cell produces are coded for by the genes it possesses or by the genes that are expressed- switched on. * The proteins modify the cell- determine the cells structure and control processes- including the expression of more genes which produce more proteins. * During the process of cell specialisation, only some of the genes of totipotent cells are expressed so only part of the DNA of a cell is translated into proteins. * Cells therefore only make the proteins they require to carry out their specialised functions and those required for essential processes. * Although the cell is capable of making other proteins, they are not needed and it would be wasteful to produce them. * To conserve energy and resources, various stimuli ensure genes for other proteins are not expressed.

Question 43

How are genes switched on or off?

Answer 43

* Controlling transcription- preventing the production of mRNA- using transcription factors, oestrogen and epigenetic tags. * Preventing translation using RNA interference (RNAi).

Question 44

How do stem cells specilase.

Answer 44

* Stem cells all contain the same genes but during development not all genes are transcribed and translated. * Stem cells become specialised because during their development they can only transcribe and translate part of their DNA. * Under one set of conditions, certain gene are expressed and others are switched off in the stem cell. * Under different conditions, different genes are expressed and others are switched off in the stem cell. * Genes that are expressed get transcribed into mRNA and translated into proteins. * Proteins modify the cell- determine the cell structure and control cell processes- including the expression of more genes which produced more proteins. * Changes in the stem cell produced by these proteins cause the cell to differentiate and become specialised.

Question 45

Describe the longevity of stem cell differentiation.

Answer 45

* Some cells, such as xylem cells and red blood cells are so specialised they lose their nuclei once they mature. As the nucleus contains the genes, these cells cannot develop into other cells.

Question 46

Give some examples of highly specialised cells.

Answer 46

* E.g. Red blood cells- produced by stem cells in the bone marrow- contain lots of haemoglobin and have no nucleus. Stem cell produces a new cell where the genes for haemoglobin production are expressed, alongside genes that involve the removal of the nucleus. Other genes are not expressed, resulting in a specialised red blood cell. * E.g. nerve cells- long axons and dendrites- connect them to other nerve cells. Produced from stem cells in the neural tube. Stem cells produce new cells where the genes that direct the axon to extend outwards are expressed. Genes that direct the dendrites to form are also expressed. Other genes are switched off. * E.g. Cardiomyocytes- see other card.

Question 47

Describe the significance of cardiomyocytes.

Answer 47

* Heart muscle cells that make-up a lot of the tissues in the heart. * Unipotent cells. * Mature mammals- cardiomyocytes can’t divide to replicate themselves. Initially this was seen as a concern by scientists who thought the heart was unable to regenerate, which could become a problem if the heart was damaged or the cells become worn through age. * However, researchers suggest the old or damaged cardiomyocytes can be replaced by new cardiomyocytes from a small supply unipotent stem cells in the heart. * The researches opinions vary on how much this process happens- some think slowly others think quickly- depends on how many times the cardiomyocytes are replaced during a person’s lifetime.

Question 48

Describe how stem cells can be used in therapies.

Answer 48

* As stem cells can divide into a range of specialised cell types, doctors and scientists think they could be used to replace cells damaged by illness or injury. * Some stem cell therapies already exist for some diseases affecting the blood and immune system. * Don’t need to know the specific treatments but helpful to know some examples.

Question 49

Describe the effect of stem-cell therapies.

Answer 49

* **Transplanted stem cells differentiate/ specialise** into healthy cells- reduce the effect of unhealthy cells (**remember to state the effect**). * **Stem cells transplanted from a close relative e.g. brother/ sister have less chance of rejection.**

Question 50

Describe how bone marrow transplants work.

Answer 50

* Bone marrow- contains stem cells that can become specialised to form any type of blood cell. * Bone marrow transplants – used to replace faulty bone marrow in patients that produce abnormal blood cells. * The patient’s faulty bone marrow is destroyed so that **there are no faulty cells that produce defective proteins or cancerous cells produced.** * The **stem cells** in transplanted bone marrow **continuously divide and replicate to produce only healthy blood cells.** * Bone marrow transplants are used to successfully to leukaemia (blood and bone marrow cancer) and lymphoma (cancer of the lymphatic system. * Can be used to treat some genetic disorders such as sickle-cell anaemia and severe combined immunodeficiency (SCID). * SCID- genetic disorder affecting the immune system- white blood cells made in the bone marrow from stem cells are defective- can’t defend the body against infections by identifying and destroying pathogens- high susceptibility to infections. * Treatment with bone marrow transplant replaces faulty bone marrow with donor bone marrow that contains stem cells without the faulty genes cause SCID. * The bone marrow cells can differentiate to produce functional white blood cells which can identify and destroy pathogens enabling the immune system to function properly.

Question 51

How are scientists researching stem cell treatments.

Answer 51

* Stem cells- can divide into specialised cell types- scientists think they could be used to replace damaged tissues in a range of diseases. * Scientists- researching the use of stem cells as a treatment for many conditions.

Question 52

Give some examples of treatments stem cells could be used for. | Don't need to know specifics just general idea.

Answer 52

* Damaged nerve tissues after spinal cord injuries. * Damaged heart tissue after heart disease and damaged caused by hear attacks. * Diseased bladder- stem cells could be used to grow whole bladders to replace diseased ones. * Diseased windpipes in respiratory diseases- donated windpipes can be stripped down to their collagen structure and covered with tissue from stem cells. * Organs- grown from stem cells and transplanted to provide new organs for people on donor waiting lists.

Question 53

What are the best types of stem cells for human stem cell therapies.

Answer 53

* Pluripotent stem cells- most desirable- can divide in unlimited numbers and can be used in treating human disorders. * Pluripotent cells- can differentiate into a wide range of different types- useful to repair damage e.g. to the heart- **can replace any type of cell. **

Question 54

What are the sources of human stem cells for therapies.

Answer 54

* Adult stem cells. * Embryonic stem cells. * Induced pluripotent stem cells (iPS cells).

Question 55

Describe how adult stem cells can be used for stem cell therapies.

Answer 55

* Obtained from body tissues of an adult e.g. bone marrow- obtained in low-risk operation. * Adult stem cells- aren’t as flexible as embryonic stem cells- can only specialise into a limited range of cells not all body cell types- unipotent or multipotent. * Scientists are trying to find ways to make adult stem cells specialise into any cell type.

Question 56

Describe how embryonic stem cells can be used for stem cell therapies.

Answer 56

* Obtained from embryos at an early stage of development. * Embryos created in a laboratory using in vitro fertilisation (IVF)- egg cells are fertilised by sperm outside the womb. * Once the embryos are approximately 4-5 days old, stem cells are removed from them and the rest of the embryo is destroyed. * Embryonic stem cells can divide an unlimited number of times and develop into all type of body cells except the placenta- pluripotent.

Question 57

Describe how iPS cells are formed?

Answer 57

* Induced pluripotent stem cells (iPS cells) can be produced from adult somatic cells using appropriate protein transcription factors. * Induced pluripotent stem cells (iPS cells) are produced from unipotent stem cells but have pluripotent capabilities. * Unipotent cell- can be any body cells- genetically altered in a laboratory to make them acquire the characteristics of embryonic stem cells- type of pluripotent cell. * Process involves reprogramming unipotent adult body cells so they can become pluripotent. * To make them acquire the new characteristics, unipotent cells are made to express a series of transcription factors that are normally associated with pluripotent stem cells. * Transcription factors cause the unipotent cells to express genes that are normally associated with pluripotent stem cells- turn on genes otherwise turned off. * Transcription factors can be introduced to unipotent cells by infecting them with a specifically-modified virus with the genes coding for the transcription factors within its DNA. * When the virus infects the adult cell, these genes are passed into the adult cell’s DNA, meaning the cell is able to produce the transcription factors. * **The transcription factors attach to a gene / the promoter region and stimulate RNA polymerase to start transcription in some places, and inhibit transcription of other genes.** * The fact genes are capable of being reactivated- shows adult cells retain the same genetic information present in the embryo.

Question 58

What are the uses of iPS cells?

Answer 58

* Induced pluripotent stem cels are useful in research and in future medicine. * Possible that iPS cells could be made from a patient’s own cells. * iPS cells- genetically identical to the patients’ cells- could then be used to grow some new tissue or an organ that the patient’s body would reject- transplants are rejected as it causes the patient’s immune system to recognise the tissue as foreign and attack it. * Can be used to regrow tissues that have been damaged by accidents or diseases. * iPS cells- capable of self-renewal- divide indefinitely to provide limitless supply. * **When iPS cells divide, they differentiate into** the target healthy cell (**state what the cell is**).

Question 59

Why can iPS cells help resolve the embroyonic stem cell problem?

Answer 59

* More research is required into how similar they are to pluripotent embryonic stem cells is needed before they can properly utilised * iPS- cells are similar to embryonic stem cells in form and function but are not exact duplicates. * Induced pluripotent stem cells- useful- potential to be as flexible as embryonic stem cells but obtained from adult tissue so aren’t same ethical issues. * Can replace embryonic stem cells in medical research and treatment and overcome ethical issues surrounding the use of embryos in stem cell research.

Question 60

What should you remember when evaluating stem cell therapies?

Answer 60

* You should be able to evaluate the use of stem cells in treating human disorders. * Remember the rules for evaluate questions when completing the answer- should be the main focus, can also add in some specific info related to the topic but focus on the experiment/ data. * Remember when evaluating with comprehension questions- don’t just read the lines specified- read a few lines above and incorporate it in answer.

Question 61

Compare gene therapy vs. stem cell therapy.

Answer 61

* Positives of stem cells vs. gene therapy: * No destruction of stem cells or bone marrow for gene therapy. * **Donors not required for gene therapy.** * ** Less/ no chance of rejection in gene therapy- own cells.** * Negatives of stem cells vs. gene therapy: * **Gene therapy- some faulty cells still produced.** * **Gene therapy could cause an immune response against the genetically modified cels/ virus.** * **Viruses could cause side effects in gene therapy.** * **iPS cells have less chance of rejection than gene therapy and only require a single treatment- long term. Gene therapy short term. **

Question 62

What are the ethical concerns surrounding embryonic stem cells?

Answer 62

* Obtaining stem cells form embryos created by IVF creates ethical issues because it results in the destruction of an embryo that could become a foetus. * Some people believe that at the moment of fertilisation, an individual is formed and has the right to life so it is wrong to destroy embryos. * Some people have fewer objections to stem cells being obtained form egg cells not fertilised by sperm but artificially start dividing because the cells couldn’t survive past a few days s and wouldn’t produce a foetus if placed in a womb. * Some people think scientists should only use adult stem cells because their production doesn’t destroy an embryo. * Adult stem cells can’t develop into all the specialised cells embryonic stem cells can. * Decision makers in society have to take into account views when making decisions about important scientific work like stem cell research and its use to treat human disorders.

Question 63

What are the benefits of stem cell therapy?

Answer 63

* People who make decisions about the stem cells to treat humans need to weigh up the benefits of stem cell therapies against the ethical concerns and health risks. * Stem cell therapies could save lives of people e.g. wating for organ transplants. * May be possible to make stem cells genetically identical to a patient’s own cell- used to grow new tissue or organ that the patient’s body wouldn’t’ reject. * Improve the quality of life for many people- e.g. replaced damaged cells for those who are blind.

Question 64

What are the risks of stem cell therapies?

Answer 64

* The stem cells may not differentiate into the right type of cell, causing a cancer and damaging other cells. * The stem cells may be rejected. * The stem cells might **divide out of control leading to a tumour/ cancer.**

Question 65

How is cell specialisation achieved.

Answer 65

* Cell specialisation- result of selective expression of certain genes out of the full identical set of genes found in every cell. * Cells are able to control their metabolic activities by regulating the transcription and translation of their genome. * Although the cells within an organism carry the same coded genetic information, they translate only part of it. * In multicellular organisms, this control of translation enables cells to have specialised functions, forming tissues and organs.

Question 66

What factors affect gene expression.

Answer 66

* Gene expression is controlled by a number of features which regulate transcription and translation. * There are many factors that control the expression of genes and, thus, the phenotype of organisms. * Some are external, environmental factors, others are internal factors. * The expression of genes is not as simple as once thought, with epigenetic regulation of transcription being increasingly recognised as important. * The regulation of gene expression is controlled by the regulation of transcription using transcription factors, oestrogen and epigenetic control, and the regulation of translation using RNA interference (RNAi). * The expression of genes can also be affected by molecules other than transcriptional factors but most of these methods e.g. oestrogen, epigenetic control, control the use of transcriptional factors.

Question 67

What is important to understand with regards to regulation of gene expression.

Answer 67

* The expression of genes is not as simple as once thought, with epigenetic regulation of transcription being increasingly recognised as important. * Consideration of cellular control mechanisms underpins the content of this section is important- transcription, translation etc. * Students who have studied this section should develop an understanding of the ways in which organisms and cells control their activities. * This should lead to an appreciation of common ailments resulting from a breakdown of these control mechanisms and the use of DNA technology in the diagnosis and treatment of human diseases.

Question 68

How is gene expression controlled through transcription?

Answer 68

* Controlling gene expression can occur by controlling transcription. * Transcription- gene copied from DNA into messenger RNA by RNA polymerase. * Transcription can be regulated using oestrogen, transcription factors and epigenetic control.

Question 69

How do transcriptional factors work?

Answer 69

* In eukaryotes, transcription of target genes can be stimulated or inhibited when specific transcriptional factors move from the cytoplasm into the nucleus. * Proteins called transcriptional factors control the rate of the transcription of genes. * Activators- transcriptional factors that stimulate or increase the rate of transcription- e.g. help RNA polymerase bind to the start of the target gene and activate transcription. * Repressors- transcription factors that inhibit or decrease the rate of transcription- bind to the start of the target gene, preventing RNA polymerase from binding, stopping transcription. * Transcriptional factors move from the cytoplasm to the nucleus. * Each transcriptional factor has a site that binds to a specific base sequence of the DNA in the nucleus called the promoter region, which are found near the start of the target genes.

Question 70

How do activator transcription factors work?

Answer 70

* When the **transcription factor binds to the promoter region of the DNA**, it causes this region of DNA to begin transcription. * **Stimulates RNA polymerase** bind to the start of the target gene and activate transcription. * Messenger RNA (mRNA) is produced and the information it carries is translated onto a polypeptide. * When a gene is not being expressed- the site on the transcriptional factor that binds to the DNA is not active. * As the site on the transcriptional factor binding other DNA is inactive, it cannot cause transcription and polypeptide synthesis.

Question 71

Describe the features of oestrogen.

Answer 71

* Oestrogen- steroid hormone that initiates gene transcription- switch on a gene. * Some hormones, such as adrenaline, operate on a second messenger mechanism, however, oestrogen operates on a lipid-soluble mechanism used by steroid hormones. * Steroid hormones- **hydrophobic and lipid soluble- diffuse through phospholipid bilayer.**

Question 72

How is transcription activated by oestrogen?

Answer 72

* Oestrogen- lipid-soluble molecule- diffuses through the phospholipids in the cell-surface membrane. * Once inside the cytoplasm, oestrogen binds with an oestrogen receptor site on a transcriptional factor, forming an oestrogen-oestrogen receptor complex. * Only target cells have the oestrogen receptor so only these cells respond to the stimulus of oestrogen. The shape of the site and shape of the oestrogen molecule have a **specific tertiary structure and are complementary.** * By binding with this site, oestrogen changes the tertiary structure of the DNA binding site on the transcriptional factor, which can now bind to DNA, meaning that the transcriptional factor is activated. * The transcriptional factor can now enter the nucleus through a nuclear pore and bind to specific base sequences on DNA near the start of the target gene. * Combination of the transcriptional factor with DNA stimulates transcription of the gene that makes up the portion of DNA.

Question 73

What is epigenetics?

Answer 73

Epigenetics involves **heritable changes in gene function, without changes to the base sequence of DNA.**

Question 74

What is the function of epigenetics.

Answer 74

* Eukaryotes- epigenetic control can determine whether a gene is expressed (switched on or off)- transcribed and translated- or not. * Works through the attachment or removal of chemical groups- epigenetic marks- to or from DNA or histone proteins. These epigenetic marks are methyl groups and acetyl groups. * Epigenetic marks don’t alter the base sequence of DNA but alter how easy it is for enzymes and other proteins needed for transcription to interact with and transcribe DNA. * While the genetic code is fixed, the epigenome is flexible.

Question 75

What is the epigenome?

Answer 75

The epigenetic marks that have been added to the entire genome.

Question 76

Describe the function of the DNA-histone complex.

Answer 76

* DNA- wrapped around histones proteins to form chromatin which makes up chromosomes- can be highly condensed or less condensed. * How condensed the chromatin is due to the DNA- histone complex affects the accessibility of the DNA and whether or not it can be transcribed. * Active genes- association of histones with DNA is weak- DNA-histone complex less condensed- DNA accessible by transcription factors- initiate production of mRNA- switch the gene on. * Inactive genes- association of histones with DNA is stronger- DNA-histone complex more condensed- DNA not accessible by transcription factors- can’t initiate the production of mRNA- gene is switched off- epigenetic silencing. * Both DNA and histones are covered in chemical tags which form a second layer known as the epigenome. * The epigenome determines the shape of the DNA- histone complex. * Condensation of the DNA-histone complex- inhibits transcription- caused by decreased acetylation of the histones or methylation of DNA.

Question 77

How do epigenetic mechanisms control gene expression?

Answer 77

* Epigenetic mechanisms used to control gene expression- methylation of DNA and acetylation of histones. * These changes are caused by changes in the environment that inhibit transcription by: * increased methylation of the DNA * Decreased acetylation histones associated with DNA.

Question 78

How does acetylation work?

Answer 78

* Histones can be epigenetically modified by the addition or removal of acetyl groups. * Acetylation is when an acetyl group is transferred to a molecule. * Acetylcoenzyme A- donates its acetyl group to histones. * When histones are acetylated, the chromatin is less condensed- means transcription factors can access the DNA, allowing genes to be transcribed. * Deacetylation- reverse reaction- acetyl group removed from a molecule. * Histone deacetylase (HDAC) enzymes are responsible for removing the acetyl. groups. * Decreased acetylation of histones- increases positive charges on histones- increases their attraction to the phosphate groups of DNA. * The association between DNA and histones is stronger- the chromatin becomes highly condensed and the DNA is not accessible to transcription factors. * Transcription factors can’t initiate mRNA production form DNA so the gene is switched off- won’t be transcribed.

Question 79

Describe how methylation works.

Answer 79

* Addition of a methyl group (CH3) to a molecule. * Methyl groups are added to the cytosine bases of DNA. * The group always attached at a CpG site- where a cytosine and guanine base are next to each other in the DNA- linked by a phosphodiester bond. * Increased methylation changes the DNA structure so that the enzymes and structures involved in transcription can’t interact with the gene so the gene isn’t expressed. * Methylation inhibits the transcription of genes in two ways: * Preventing the binding of transcription factors to DNA. * Attracting proteins that condense the DNA-histone complex- by inducing deacetylation of the histones, making the DNA inaccessible to transcription factors.

Question 80

Summarise the effects of methylation.

Answer 80

* **Increased methylation of DNA/ gene/ allele- inhibits/ prevents transcription.** * **Decreased methylation of DNA/ gene/ allele- stimulates transcription.**

Question 81

Summarise hte effects of acetylation.

Answer 81

* **Decreased acetylation of histones- inhibits transcription.** * **Increased acetylation of histones- stimulates transcription. **

Question 82

What molecules do oestrogen, methyl and acetyl groups bind with.

Answer 82

* **Oestrogen binds with protein.** * **Methyl groups bind with DNA.** * **Acetyl groups bind with protein.**

Question 83

Describe how epigenetics explain the influence of the environment on genetics.

Answer 83

* While genes determine the features of an organism, the environment influences the expression of these genes. * Epigenetic changes to gene expression play a role in many normal cellular processes and can also occur in response to changes in the environment e.g. pollution/ availability of food. * Epigenetic markers respond to environmental changes- factors like diet and stress cause chemical tags to adjust the condensation (wrapping and unwrapping) of DNA and switch genes on/ off. * Epigenetics helps to explain the environmental causes of some illnesses, including diabetes and cancer. * Epigenetics explain when diseases e.g. Huntington’s start depending on how methylated or acetylated the genes that are causing them are.

Question 84

Describe how inheritance relates to epigenetics.

Answer 84

* Organisms- inherit DNA base sequence from their parents. * The environmental changes to the phenotype can also cause heritable changes in gene function without changing the base sequence of DNA due to epigenetics. * Epigenetics- explains how environmental influences such as diet can alter the genetic inheritance of an organism’s offspring. * The expression of some genes in offspring can be affected by environmental changes which affected their parents or grandparents e.g. plant response to drought- passed on to later generations. * Inheritable epigenetics enables a review into the theories of evolution suggesting characteristics acquired during an organism’s life could be passed onto future generations.

Question 85

Describe how the epigenome develops in the womb and throughout life.

Answer 85

* Epigenome of a cell- accumulation of all the signals it has received during its lifetime- acts as a cellular memory. * Most epigenetic marks on the DNA are removed between generations- during the earliest stages of development, a specialised cellular mechanism searches the genome and erases its epigenetic tags to reset the epigenome, but some escape the removal process and pass unchanged from parent to offspring. * In early development, signals that come from within the cells of the foetus and nutrition provided by the mother are important in shaping the epigenome. * After birth, environmental factors affect the epigenome and signals from within the body, for example hormones also influence it- factors cause the epigenome to activate or inhibit specific sets of genes.

Question 86

Describe how the environment works to alter the epigenome.

Answer 86

* After birth, environmental factors affect the epigenome and signals from within the body, for example hormones also influence it- factors cause the epigenome to activate or inhibit specific sets of genes. * The environmental signal stimulates proteins to carry messages inside cells from where they passed by a series of other proteins into the nucleus. * The message passes to a specific protein which can be attached to a specific sequence of bases on the DNA. * Once attached, the protein has two possible effects: * Changing the acetylation of the histones leading to the activation or inhibition of a gene. * Change the methylation of DNA by attracting enzymes that can add or remove methyl groups.

Question 87

Describe some examples of how the epigenome is inherited. | Probability don't need to know this.

Answer 87

* Experiments on rats show that good maternal behaviour in rats transmits epigenetic information to their offsprings DNA- female offspring who receive good care when young nurture their offspring better. * Humans- if the mother has gestational diabetes- foetus exposed to high concentrations of glucose- cause epigenetic changes increasing the likelihood the offspring will develop gestational diabetes.

Question 88

How do epigenetics relate to diseases.

Answer 88

* Epigenetic changes are part of normal development and health but can also be responsible for certain diseases. * Epigenetics helps to explain the environmental causes of the development of some diseases, including diabetes and cancer. * Altering any epigenetic processes can cause abnormal activation or silencing of genes. * Alterations- associated with a number of diseases including cancer.

Question 89

Give some examples of how epigenetics can lead to diseases. | Don't need to know the specifics in too much depth

Answer 89

* Abnormal methylation of tumour suppressor genes and oncogenes can cause cancer (see notes further down) * Epigenetics also plays a role in many other diseases for example Fragile C syndrome, Angelman syndrome and Prada-Willi syndrome. * These syndromes can be caused by a mutation resulting in the DNA sequence CGG being repeated more times than usual- more CpG sites- increased methylation- switches the gene off so the protein the gene codes for isn’t produced. E.g. fragile-X syndrome. * Syndromes can also occur due to a mutation resulting in a region of a gene/ chromosome becoming mutated on one of the homologous pair. The other chromosome in the homologous pair may contain the full gene to produce the correct protein but this may be switched off by methylation so the gene is not transcribed and the protein is not produced e.g. Prader-Willi syndrome and Angelman syndrome.

Question 90

How do epigenetic treatments work.

Answer 90

* Many diseases are triggered by epigenetic changes that cause certain genes to be activated or silenced, so epigenetic treatments can counteract these changes. * Epigenetic changes are reversible, making them good targets for drugs to combat diseases they cause. * Treatments use drugs to inhibit certain enzymes involved in either histone acetylation or DNA methylation.

Question 91

How do drugs that affect enzymes in the epigenome work.

Answer 91

**Drugs that affect enzymes- bind to active site, cannot methylate/ deacetylate the promoter region of the gene, transcriptional factors can bind, RNA polymerase is stimulated to produce mRNA.**

Question 92

How can drugs be used to cure problems caused by epigenetics.

Answer 92

* Increased methylation- epigenetic change that leads to gene being switched off. Drugs that inhibit enzymes that cause DNA methylation- reactivate genes that have been silenced- sometimes used to treat diseases caused by this. * Decreased acetylation of histones can also result in genes being switched off- can result in diseases/ cancer. Some drugs work by inhibiting the activity of histone deacetylase (HDAC) enzymes- responsible for removing acetyl groups from histones. Without HDAC enzymes activity, genes remain acetylated and the proteins they code for can be translated.

Question 93

Why is it important that epigenetic therapeies are targetted?

Answer 93

* Epigenetic changes usually take place in a lot of cells so it’s important to make the drugs specifically target diseased cells, as if the drugs affected normal cells, they could activate gene transcription and make cells cancerous. * E.g. drugs used in cancer therapies- designed to only target dividing cells to avoid damaging normal body cells.

Question 94

How can epigenetics be used in diagnostic tests?

Answer 94

* Tests can be used to detect the early stages of disease such as cancer, brain disorders and arthritis. * Double-stranded RNA can be made by in vitro transcription of a DNA template using the polymerase chain reaction. * Tests can identify the level of DNA methylation and histone acetylation at an early stage of disease. * Allows those with disease to seek early treatment and have a better chance of being cured.

Question 95

Describe RNA interferance (RNAi).

Answer 95

* In eukaryotes and some prokaryotes, gene expression can be controlled by inhibiting the translation of mRNA produced by a target gene by RNA interference (RNAi) * The translation of mRNA can be inhibited by breaking down mRNA before its coded information can be translated into polypeptides. * RNAi is where small, double stranded RNA molecules stop mRNA from target genes being translated into proteins by breaking mRNA down. * The molecule involved in RNAi are siRNA (small interfering RNA) and miRNA (microRNA).

Question 96

Describe how siRNA works in RNA interferance (RNAi).

Answer 96

* An enzyme cuts large double-stranded molecules of RNA into smaller sections called small interfering RNA (siRNA). * One of the two siRNA strands combines with an enzyme, the other strand is broken down. * Once the target mRNA has been transcribed, it leaves the nucleus for the cytoplasm. * The siRNA molecule guides the enzyme to the target mRNA molecule by pairing its base sequence with complementary ones on a section of the target mRNA molecule- binds to the mRNA and destroys it. * Once in position, the enzyme cuts the mRNA into smaller fragments that cannot be translated into a polypeptide. * The gene hasn’t been expressed as the mRNA can’t be translated so the gene is blocked, so less of the protein coded for by the gene is produced.

Question 97

When interpreting RNAi what should you consider?

Answer 97

* Look out for hidden RNAi involving complementary mRNA with the prefix ‘anti’: * **Antisense mRNA complementary to sense mRNA.** * **Antisense mRNA binds to sense mRNA and a double stranded mRNA forms.** * **Ribosomes wouldn’t be able to bind.** * **Prevents translation of mRNA and less production of the protein.**

Question 98

How can single-stranded cDNA be used to prevent transcription in a form of RNA interference (RNAi).

Answer 98

* **Binds to the gene, DNA, mRNA, transcription factor DNA or promoter **(not transcription factor) as it is **complementary to it.** * This **prevents translation. **

Question 99

Describe the use of miRNA in plants. | Probably not going to come up in the exam.

Answer 99

* A similar process to siRNA happens with miRNA in plants. * Like siRNA the base sequence of plant miRNA is complementary to its target mRNA sequence and binding results in the cutting up and degradation of the mRNA. * The production of miRNA in the cell is similar to mammalian miRNA.

Question 100

How does miRNA work in mammals.

Answer 100

* miRNA isn’t usually fully complementary to the target mRNA- less specific than siRNA so may target more than one mRNA molecule. * When miRNA is first transcribed, it is a long, folded strand which is processed into a double strand and then two single strands by enzymes in the cytoplasm. * Like siRNA, open strand associated with proteins and binds to target mRNA in the cytoplasm. * Instead of the proteins associated with miRNA cutting mRNA into fragments the miRNA-protein complex physically blocks the translation of target mRNA. * mRNA is moved into a processing body where it can either be stored or degraded. * Where it is stored, it can be returned and translated another time.

Question 101

How do you interpret data provided from investigations into gene expression.

Answer 101

* Could be about transcription factors, oestrogen, RNAi or epigenetic control of gene expression. * May need to interpret the results of an experiment in a table, bar chart, scatter graph or frequency table. * **May need to interpret flow diagrams of which molecules are bound at each stage- read carefully for which stage the question is asking for and list the molecules at each stage.** * Need to understand what the presence of a transcriptional factor means- e.g. whether an enzyme is present or not. * May be asked to suggest what the effect of a mutation has done to the transcription rate/ the structure of the protein.

Question 102

How do you evaluate data related to the phenotype.

Answer 102

* May need evaluate appropriate data for the relative influences of genetic and environmental factors on phenotype. * Phenotype- result of the genotype and its interaction with the environment. * Environmental factors that can affect the epigenome include diet, physical exercise and stress. * It is sometimes difficult to evaluate which features have a risk more to do with the genotype or the environment. * E.g. overeating could be due to increased food availability or due to decreased dopamine receptors due to an allele. * Studies of identical twins- useful in determining whether factors or due to the environment or genetics. * Twins- genetically identical so differences in phenotype are due to environmental factors. * Identical twins have similar epigenetic marks when they are born and in the first years of their life. * Different epigenetic changes occur in each twin as they get older. * If characteristics are very similar in identical twins, genetics plays more important role. * If characteristics are different between twins, environment must have a larger influence. * Data that comes from twin studies involving a large sample size is better for drawing valid conclusions than data based on a small sample size. * Large sample size more representative.

Question 103

What is cancer?

Answer 103

* Cancer- group of diseases caused by damage to genes that regulate mitosis in the cell cycle- leads to unrestrained growth of cells. * Cancer is common and destructive but is avoidable and treatable if diagnosed early.

Question 104

What is a tumour?

Answer 104

* Tumour- a group of abnormal cells- develops and constantly expands in size. * Tumours are cancers if they invade and destroy surrounding tissues. * Tumours can develop for years without obvious symptoms and can be large by the time they are discovered.

Question 105

How do tumours differ from normal cells?

Answer 105

* Nucleus is larger and darker than in normal cells, and sometime shave more than one nucleus. * Have irregular shape. * Don’t produce the proteins needed to function correctly. * Have different antigens on their surface. * Don’t respond to growth regulating processes. * Divide by mitosis more frequently by normal cells.

Question 106

Describe the features of malignant tumours.

Answer 106

* Are cancers- invade and destroy surrounding tissues. * Can grow to a large size. * Grow rapidly. * Cell nucleus is often larger and appears darker due to an abundance of DNA. * The cells become de-differentiated- unspecialised. * Cells do not produce adhesion molecules so they tend to break off the tumour and spread to other regions of the body- in metastasis, forming secondary tumours from primary tumours. * Tumours are not surrounded by a capsule and so can grow finger-like projections into surrounding tissues. * More likely to be life threatening as abnormal tumour tissue replaces normal tissue. * Often have system- whole body- effects- weight loss and fatigue. * Removal involves radiotherapy and/or chemotherapy as well as surgery. * More frequently reoccur after treatment.

Question 107

Describe how malignant tumours spread.

Answer 107

* Cells do not produce adhesion molecules so they tend to break off the tumour and spread to other regions of the body- in metastasis, forming secondary tumours from primary tumours: * The enlarging primary tumour develops blood and lymphatic vessels. * Tumour cells squeeze into blood and lymphatic vessels. * In blood vessels, tumour cells travel by the blood and circulate, they adhere to blood vessel walls and squeeze through to form distant metastases. * In the lymph system, tumour cells metastasise in lymph nodes.

Question 108

Describe benign tumours.

Answer 108

* Non-cancerous. * Cells of benign tumours **cannot spread to other parts of the body- metastasis- and invade neighbouring tissues- main way they differ.** * Can grow to a large size. * Grow very slowly. * Cell nucleus has a relatively normal appearance. * Cells often well-differentiated- specialised. * Primary tumours- remain within the tissue they occurred in- cells produce adhesion molecules that make them stick together so they remain within the tissue. * Tumours are surrounded by a capsule of dense fibrous tissue which stops the cells invading other tissues. * Less likely to be life-threatening but can disrupt the function of vital organs and cause blockages. * Localised effects. * Can be removed by surgery alone. * Rarely reoccur after treatment. * Can become malignant.

Question 109

How are cancer cells formed?

Answer 109

* Cancer cells are often derived from a single mutant cells- the initial mutation causes uncontrolled mitosis. * Further mutation in one of the cells produced from the mutant cell can lead to other changes that cause subsequent cells to be different from normal cells in growth and appearance. * Two types of genes control cell division and are the main genes that play a role in cancer- tumour suppressor genes and proto-oncogenes. Mutations in these genes cause cancer.

Question 110

What do proto-oncogenes do and what does a mutation in one cause?

Answer 110

* Proto-oncogenes stimulate cell division when growth factors attach to a protein receptor on the cell-surface membrane. This then activates the gene to produce proteins that stimulate cell division by causing DNA to replicate and the cell to divide. * Oncogenes- are mutations of proto-oncogenes. Cause the gene to be overactive and stimulate the cell to divide too rapidly and uncontrollably, increasing the rate of division, resulting in a tumour or cancer.

Question 111

What happens to proto-oncogenes when they're mutated?

Answer 111

* If a proto-oncogene mutates into an oncogene it can become permanently activated because: * The receptor protein on the cell-surface membrane can be permanently activated so the cell division is switched on even in the absence of growth factors. * The oncogene may code for a growth factor that is then produced in excessive amounts, stimulating excessive cell division.

Question 112

What is the difference between inherited and acquired cancer.

Answer 112

* Some cancers are caused by inherited mutations of proto-oncogenes that cause the oncogene to be activated but most cancer-causing mutations involving oncogenes are acquired not inherited. * If mutations in individual cells after fertilisation- acquired mutations- occur in genes that control the rate of cell division by mitosis- causes uncontrolled cell division resulting in a tumour.

Question 113

What do tumour suppressor genes do?

Answer 113

* Tumour suppressor genes- slow cell division, repair mistakes in DNA and code for apoptosis (programmed cell death)- opposite to proto-oncogenes. * They do this by coding for proteins that stop cells dividing or cause them to perform apoptosis. * The genes maintain normal rates of cell division and prevent the formation of tumours.

Question 114

What happens to a tumour supressor gene if it becomes mutated?

Answer 114

* While oncogenes cause cancer as a result of activation of proto-oncogenes, tumour suppressor genes cause cancer when they are inactivated. * **If a tumour suppressor gene becomes mutated it can be inactivated- switched off- amino acid sequence/ primary structure of protein it codes for is altered.** * Stops inhibiting **cell division and cells divide rapidly and uncontrollably**, resulting in a tumour. * Mutated cells formed are usually structurally and functionally different from normal cells. * While most cells die, those that survive can make clones of themselves and form tumours. * Forms of tumour suppressor gene include TP53, BRCA1 and BRCA2. * E.g. mutation in the TP53 gene cause the p53 protein involved in apoptosis when a cell is unable to repair its DNA to not function correctly. Cells with damaged DNA then continue to divide leading to cancer.

Question 115

How are tumour supressor genes produced.

Answer 115

Some cancers are caused by inherited mutations of tumour suppressor genes but most mutations are acquired.

Question 116

How does gene expression affect cancer.

Answer 116

* Tumours and tumour growth can be caused by abnormal methylation and increased exposure to oestrogen. * Activation of a normally inactive gene or inactivation of a normally active gene can also cause cancer. * Some patients with cancer have less DNA methylation and have higher than normal gene activity. * There are specific sections of DNA near promoter regions that have no methylations in normal cells. However, in cancer cells these regions become highly methylated, causing genes that should be active to switch off. * Epigenetic changes do not alter sequence of bases in DNA but can increase the incidence of mutations. * Some active genes normally help repair DNA and so prevent cancers. * In people with inherited cancer, increased methylation of these genes can lead to protective genes being switched off, causing damaged base sequences in DNA to not be repaired, leading to cancer.

Question 117

How does abnormal DNA methylation cause cancer.

Answer 117

* Common in tumours. * Hypermethylation (increased methylation): * Most common. * **Increased methylation- methyl groups added to the promoter region of (both copies of) a tumour suppressor gene.** * This leads to the** tumour suppressor gene is not transcribed or expressed- inhibited** inactivated or silenced- switched off. * The genes transcription is inhibited so they are **not able to produce proteins that prevent cell division/ cause cell death/ apoptosis.** * **Cells divide rapidly and uncontrollably by mitosis** and tumours can develop. * Abnormal methylation can occur in tumour suppressor gene BRCA1- leads to the development of breast cancer. * Hypomethylation (reduced methylation): * Occurs in proto-oncogenes- causes them to act as oncogenes. * Decreased methylation leads to increased activation of the gen- increasing the production of proteins that encourage cell division. * Stimulates cells to divide uncontrollably- forms tumours.

Question 118

What role does oestrogen have in cancer.

Answer 118

Increased oestrogen concentrations play a role in the development of some breast cancers.

Question 119

How does oestrogen cause cancer.

Answer 119

* Oestrogen regulates the menstrual cycle. * Menopausal women- produce less oestrogen from the ovaries but have increased oestrogen concentration as fat cells of the breasts break down to produce more oestrogen after menopause. Starting the menopause later than usual can increase exposure to oestrogen. * Increased oestrogen may also be the result of starting menstruation earlier than usual. * Oestrogen-containing drugs such as HRT also increase oestrogen. * Increased exposure to oestrogen over an extended period of time increases the risk of developing cancer, especially breast cancer in women. * Locally produced oestrogens- trigger breast cancer in postmenopausal women.

Question 120

How does oestrogen cause breast cancer.

Answer 120

* The exact reasons why increased oestrogen leads to cancer aren’t fully understood, but some theories suggest how oestrogen contributes to the development of breast cancers: * Oestrogen stimulates certain breast cells to divide and replicate. More cell division occurring increases the chances of mutations occurring, so there is an increased chance of cells becoming cancerous. * Oestrogen activates genes by binding to a gene that promotes transcription. If the gene that oestrogen acts on controls cell division and growth, it will be activated and continued division could produce a tumour. * Oestrogen can cause proto-oncogenes of cells in breast tissue to develop into oncogenes, leading to the development of a tumour. * Oestrogen’s ability to stimulate cell division could also mean if cells become cancerous their rapid replication could be further assisted by oestrogen, helping tumours form quickly. * Oestrogen could also introduce mutations directly into the DNA of certain beast cells, increasing the chance of the cells becoming cancerous.

Question 121

How can the production of a tumour worsen oestrogen concentrations, further worsening the cancer.

Answer 121

* Once a tumour has developed- this further increases oestrogen concentration- leads to increased development of the tumour. * White blood cells that are drawn to the tumour increase oestrogen production- leads to increased development of the tumour.

Question 122

How do you interpret data on cancer.

Answer 122

May need to evaluate evidence showing correlations between genetic and environmental factors and various forms of cancer

Question 123

How do risk factors affect cancer.

Answer 123

* Risk factors can increase the risk of cancer. * Cancer doesn’t have a single cause but scientists can identify different risk factors which increase a person’s chance of getting cancer. * Factors can be genetic or environmental. * Cancer can have an increased risk by age and genetic factors, alongside lifestyle factors.

Question 124

What genetic factors are linked to cancer.

Answer 124

Genetic factors- cancers are linked with specific inherited alleles, if the allele is inherited it increases the likelihood of getting that type of cancer- e.g. mutations of the BRCA1 gene can increase chances of a woman developing breast cancer.

Question 125

What environmental factors affect cancer.

Answer 125

Environmental factors- exposure to radiation and carcinogenic factors and lifestyle choices such as smoking, alcohol consumption and high-fat diet are linked with increase chances of cancer.

Question 126

How does risk of cancer increase with age?

Answer 126

Risk of cancer also increases with age- as natural mutation rates are slow, it takes time for tumour suppressor genes or proto-oncogenes to mutate, risk increases with age as more mutations have occurred.

Question 127

What lifestyle factors contribute to cancer?

Answer 127

* Smoking and passive breathing of tobacco smoke. * Diet- eating healthy diet reduces risk of cancer. * Obesity- being overweight increases the risk of cancer. * Physical activity- regular exercise- decreases the risk of cancer. * Sunlight- more exposed to sunlight means greater risk of skin cancer.

Question 128

Why is data on cancer risk factors difficult to interpret.

Answer 128

* Data on risk factors- difficult to interpret because characteristics can be affected by many different genes- polygenic, and many environmental factors. * It is often difficult to know which factors (genes or environment) are having the greatest effect and it makes it hard to draw conclusions on the causes of variation.

Question 129

What should you do when describing graphs on risk factors.

Answer 129

* State the correlation between individual factors and the incidence of cancer- in the case of cancer and risk factors usually a positive correlation. * If there are two factors graphed describe the link between both e.g. age decreases the effect of family history. * Look for consistencies e.g. always more likely to develop cancer if members of family have cancer. * Look for what the data suggests e.g. if to do with family history could be a genetic link. * Draw conclusions- if there are lots of factors on a graph it is difficult to tell which factor has the largest effect. * Other environmental factors may be involved in increasing the risk of developing cancer not considered in the graph. * May be asked to calculate the rate of cell division/ number of cells in a cancer.

Question 130

How have scientists concluded smoking was carcinogenic.

Answer 130

* Initial evidence of smoking and cancer was correlational, but it was backed up by experiments showing causation- the chemical components of smoking were split up and analysed for their ability to cause damage to cells. * Experiments found that tar in cigarette smoke contained carcinogens including benzopyrene which mutates DNA.

Question 131

How do mutations differ with regards to tumour supressor genes and proto-oncogenes and how does this explain the risks associated with them.

Answer 131

* It only takes a single mutated alleles to activate proto-oncogenes but it can take a mutation of both alleles to inactivate tumour suppressor genes. * Therefore, mutations in tumour suppressor genes** may have no effect in diploid heterozygous organisms as there is still a functional protein produced. ** * As natural mutation rates are slow, it takes time for both tumour suppressor alleles to mutate- explains why the risk of cancers increases with age. * Some people are born with one mutated allele- this increased the risk of cancer as they only need one further mutation rather than two- explains why some cancers have an inherited increased risk.

Question 132

When asked about the causes of cancer how should you explain it.

Answer 132

* Read the information in the question and answer in a step by step fashion/ * E.g. **broken DNA not repaired as the enzyme will not bind, uncontrolled cell division- tumour forms, tumour suppressor gene not activated/** oncogene activated.

Question 133

How do you need to understand cancer treatments.

Answer 133

May need to interpret information relating to the way in which an understanding of the roles of oncogenes and tumour suppressor genes could be used in the prevention, treatment and cure of cancer.

Question 134

Why is studying cancer important.

Answer 134

* Knowledge of the role of genes in cancer and how they work is helpful with coming up with ways to prevent, treat and cure cancer. * If a specific cancer-causing mutation is known it is possible to screen for the mutation in a person’s DNA e.g. mutated alleles of the BRCA1 gene. * Knowing of a person’s increased risk means more preventative steps can be taken e.g. women with the mutated BRCA1 gene may remove their breasts to reduce the risk of breast cancer. * People with increased risk can be screened more often so early diagnosis can increase chances of recovery. * More sensitive tests for mutations can be developed leading to earlier and more accurate diagnosis. * Treatment for cancer is different for different mutations so knowing how specific mutations cause cancer is helpful in developing drugs to target them.

Question 135

How can cancers be treated.

Answer 135

* Using drugs specific to the type of cancer. * Gene therapy where faulty alleles in a person’s cells are replaced by working versions of those alleles may also be able to treat cancer caused by some mutated alleles.

Question 136

How do drugs to treat cancer work. | Hint: 3 detailed points.

Answer 136

* Inhibiting mutated enzymes: * In TSGs- **bind to active site, cannot methylate**/ deacetylate **the promoter region of the gene, reduces methylation of DNA**/ increases acetylation, **transcriptional factors can bind to the promoter region, RNA polymerase is stimulated to produce mRNA, the gene is transcribed, preventing uncontrollable rapid cell division. ** * E.g. skin cancer caused by a mutation of the B-RAF proto-oncogene can be treated with drugs that inhibit the mutated B-RAF enzyme, stopping cells that express the mutation from growing. * Binding to altered protein receptors to suppress cell division and tumour growth e.g. breast cancer caused by a mutation of the HER2 proto-oncogene can eb treated by a drug that binds to the altered protein receptor and suppresses cell division ad tumour growth. * Using molecules which block mutated enzymes involved in repairing DNA in cancerous cells containing faulty genes, killing the cells. E.g. this treatment is being researched for mutations in faulty BRCA tumour suppressor genes.

Question 137

Why is it important to identify mutations.

Answer 137

* These drugs are targeted to certain mutations but ineffective against others, it is therefore important to identify the right mutations. * Some cancer-causing mutations require more aggressive treatments than others, so understanding how the mutation that causes them works helps provide the best treatment plan. * E.g. if a mutation is known to cause an aggressive cancer, it may be treated with higher doses of radiotherapy or by removing larger areas of the tumour and surrounding tissue during surgery.

Question 138

What must you remember when interpreting data on cancer treatment.

Answer 138

* When interpreting data on this- use the rules of evaluate questions when assessing conclusions. * Arguments for: * Find a significant difference/ change. * Usually data based. * Arguments against: * **Only investigated in one type of cancer/ organism- may not work in others.** * **Other causes of cancer- only works on one cause (specify which one).** * **No significant changes/ significant changes only above a certain point.** * **Unknown the concentrations of a molecule in certain dietary items.** * **Only reduces growth rate/ does not kill all cancer cells- no evidence of cancer being cured.** * **Experiment performed outside of the body- in vivo cells in the body might respond differently.**