8A Mutations and gene expression

Question 1

Types of mutation

Answer 1

Duplication
Addition
Deletion
Substitution
Inversion - a sequence of bases is reversed
Translocation - a sequence of bases is moved from one location in the genome to another, within or between chromosomes
Gene mutations occur spontaneously

Question 2

What is a frameshift?

Answer 2

When a mutation changes the number of bases in the DNA code this causes a frameshift in the base triplets that follow so the triplet code is read in a different way

Question 3

What do mutagenic agents do?

Answer 3

Chemicals called base analogs can substitute for a new base during DNA replication
They can delete or alter bases
They can change the structure of DNA which causes problems during DNA replication

Question 4

What is an acquired mutation?

Answer 4

A mutation that occurs in an individual cell after fertilisation
If these mutations occur in the genes that control cell division the result can be uncontrolled cell division

Question 5

What is a tumor suppresser gene?

Answer 5

When functioning normally they slow cell division by producing proteins that stop cells dividing or cause apoptosis
They can be inactivated if a mutation occurs in the DNA sequence
If a mutation occurs in a tumour suppressor gene the protein isn’t produced, the cells divide uncontrollably resulting in a tumour

Question 6

What is a proto-oncogene

Answer 6

A mutated proto-oncogene is called an oncogene
When functioning normally they stimulate cell division by producing proteins that make the cell divide
The effect can be increased if a mutation occurs in the DNA sequence
If a mutation occurs in a proto-oncogene it can become overactive and cells divide uncontrollably resulting in a tumour

Question 7

What is a malignant tumour

Answer 7

Malignant tumours are cancers
They grow rapidly and invade and destroy surrounding tissues
Cells can break off the tumours and spread to other parts of the body in the bloodstream or lymphatic system

Question 8

What is a benign tumour

Answer 8

Not cancerous
Usually grow slower than malignant tumours
Often covered in fibrous tissue that stops cells invading other tissues
Often harmless but they can cause blockages and put pressure on organs
Some can become malignant

Question 9

How do tumour cells differ in appearance from normal cells?

Answer 9

Irregular shape
Nucleus is larger and darker than in normal cells
Cells can sometimes have more than one nucleus
They don’t produce all the proteins needed to function correctly
Different antigens on their surface
Don’t respond to growth regulating processes
They divide by mitosis more frequently

Question 10

What is methylation?

Answer 10

Adding a methyl group onto something
It’s an important method of regulating gene expression (it can control whether or not a gene is transcribed and translated)

Question 11

How does abnormal methylation of cancer-related genes cause tumour growth?

Answer 11

Hypermethylation of hypomethylation can become a problem
When tumour supressor genes are hyper methylated the genes aren’t transcribed so the proteins produced to slow cell division aren’t made

Hypomethylation of proto-oncogenes causes them to act as oncogenes, increasing the production of the proteins that encourage cell divison

Question 12

How do increased levels of oestrogen contribute to some breast cancers?

Answer 12

Oestrogen can stimulate breast cells to divide and replicate. This naturally increases the chance of mutations occurring and so increases the chance of cells becoming cancerous
If cells do become cancerous their rapid replication could be further assisted by oestrogen helping tumours form quickly

Question 13

Name some genetic and environmental factors that affect the risk of cancer

Answer 13

Specific inherited alleles
Radiation
Smoking
Alcohol consumption
High-fat diet

Question 14

What is a multipotent stem cell?

Answer 14

Able to differentiate into a few different types of cell
Red and white blood cells can be formed from multipotent stem cells in the bone marrow
Found in mature mammals

Question 15

What is a unipotent stem cell?

Answer 15

Can only differentiate into one type of cell
Found in mature mammals

Question 16

What are stem cells?

Answer 16

Unspecialised cells that can develop into other types of cell
Found in the embryo

Question 17

How do stem cells become specialised?

Answer 17

All stem cells contain the same genes but during development not all of them are transcribed and translated
mRNA is only transcribed from specific genes
The mRNA from these genes is then translated into proteins
These proteins modify the cell and determine cell structure and processes which also includes the expression of more genes and more translation
These changes cause the cell to become specialised

Question 18

What are cardiomyocytes?

Answer 18

Heart muscle cells
In mature mammals its thought they can’t divide and replicate themselves
Though some think there is some regenerative capability
Scientists think old or damaged cardiomyocytes can be replaced by new cardiomyocytes derived from a small supply of unipotent stem cells in the heart
Some believe it’s a slow process and some think it’s occurring more quickly

Question 19

What is a totipotent cell?

Answer 19

Can divide and produce any type of cell
They only occur for a limited amount of time in early mammalian embryos

Question 20

Where are pluripotent cells found?

Answer 20

In embryos
Can divide in unlimited numbers and can be used to treat human disorders

Question 21

What are induced pluripotent stem cells?

Answer 21

iPS
Can be produced from adult somatic cells using appropriate protein transcription factors

Question 22

Stem cell therapies - bone marrow transplants

Answer 22

Bone marrow contains stem cells that can become specialised to form any type of blood cell
Bone marrow transplants can be used to replace faulty bone marrow in patients that produce abnormal blood cells
This technique has been used successfully to treat leukaemia (a cancer of the blood or bone marrow) and lymphoma (a cancer of the lymphatic system)
It can also be used to treat genetic disorders such as sickle-cell anaemia and severe combined immunodeficiency

Question 23

Benefits of using stem cells in medicine

Answer 23

They could save many lives e.g. people waiting for organ transplants
They could improve the quality of life e.g. replacing damaged cells in the eyes of blind people

Question 24

Adult stem cells

Answer 24

Obtained from the body tissues of an adult (e.g. from bone marrow)
Simple operation with very little risk but a lot of discomfort
Adult stem cells aren’t as flexible as embryonic stem cells because they’re multipotent

Question 25

Embryonic stem cells

Answer 25

Obtained from embryos at early stages of development
Created in a laboratory using in vitro fertilisation (IVF)
Once the embryos are approximately 4-5 days old the stem cells are removed and the rest of the embryo destroyed
Embryonic stem cells can divide an unlimited number of times and can develop into all types of body cells - they’re pluripotent

Question 26

iPS cells

Answer 26

Created in the lab
The process involves reprogramming specialised adult body cells so that they become pluripotent
They’re made to express a serios of transcription factors that are associated with pluripotency
Transcription factors can be introduced into the adult cells by infecting them with a specially modified virus. The virus has the genes coding for the transcription factors within its DNA

Question 27

Ethical issues surrounding embryonic stem cell use

Answer 27

Some believe the moment of fertilisation is when an individual is formed and so they have the right to life
Stem cells obtained from egg cells can be artificially activated to start dividing and wouldn’t survive more than a few days if placed in the womb
Induced pluripotent cells could prove really useful as they have the potential to be as flexible as embryonic stem cells but there aren’t the same ethical issues
iPS could be made from a patient’s own cells so would be genetically identical and reduce the risk of rejection

Question 28

How do transcription factors work in eukaryotes?

Answer 28

Move from the cytoplasm into the nucleus
They bind to specific DNA sites near the start of their target genes
They control expression by controlling the rate of transcription
Activators stimulate or increase the rate of transcription by helping RNA polymerase bind to the start of the gene
Repressors inhibit or decrease the rate of transcription by binding to the start of the target gene and preventing RNA polymerase from binding

Question 29

How does oestrogen initiate the transcription of target genes?

Answer 29

Oestrogen is a steroid hormone that can affect transcription by binding to a transcription factor called an oestrogen receptor forming an oestrogen-oestrogen receptor complex
This complex moves from the cytoplasm into the nucleus where it binds to specific DNA sites near the start of the target gene
The complex can act as an activator of transcription e.g. helping RNA polymerase bind to the start of the target gene
Can either act as a repressor or activator

Question 30

What is RNAi?

Answer 30

In eukaryotes gene expression is also affected by RNA interference (RNAi)
RNAi is where a small, double stranded RNA molecule stops mRNA from target genes being translated into proteins
A similar process can also occur in prokaryotes
The molecules involved are siRNA (small interfering RNA) and miRNA (microRNA)

Question 31

siRNA (and miRNA in plants)

Answer 31

mRNA leaves the nucleus for the cytoplasm after transcription
Double stranded siRNA associates with several proteins and unwinds
A single strand then binds to target mRNA
The base sequence of the siRNA is complementary to the base sequence in sections of the mRNA
The proteins associated with the siRNA cut the mRNA into fragments so it can no longer be translated
The fragments then move into a processing body which contains tools to degrade them

Question 32

miRNA in mammals

Answer 32

miRNA isn’t usually fully complementary to the target mRNA
This makes it less specific than siRNA so it may target more than one mRNA molecule
It associates with proteins and binds to target mRNA in the cytoplasm
The miRNA protein complex physically blocks the translation of the target mRNA
The mRNA is then stored in a processing body where it’s either stored or degraded
When it’s stored it can be returned and translated at another time

Question 33

How are epigenetic changes inherited by offspring?

Answer 33

Organisms inherit their DNA base sequences from their parents
Most epigenetic marks on the DNA are removed between generations but some escape removal processes and are passed onto offspring
This means the expression of some genes in the offspring can be affected by environmental changes that affected their parents or grandparents

Question 34

How does epigenetic control work in eukaryotes?

Answer 34

Epigenetic control can determine whether or not a gene is switched on or off
It works through the attachment or removal of chemical groups (known as epigenetic marks) to or from DNA or histone proteins
These epigenetic marks don’t alter the base sequence of DNA
They instead alter how easy it is for enzymes and other proteins needed for transcription to interact with and transcribe the DNA
They play a role in normal cellular processes and occur in response to changes in the environment

Question 35

How does increased methylation of DNA switch a gene off?

Answer 35

The group always attaches at a CpG site - where cytosine and guanine bases are linked by a phosphodiester bond
Increased methylation changes the DNA structure so that transcriptional machinery can’t interact with the gene, so the gene isn’t expressed

Question 36

How does decreased acetylation of histones switch genes off?

Answer 36

Histones can be epigenetically modified by the addition or removal of acetyl groups
When histones are acetylated the chromatin is less condensed which means transcriptional machinery can access the DNA allowing it to be transcribed
The removal of acetyl groups from the histones means the chromosome becomes less condensed and the genes in the DNA can’t be transcribed because the transcriptional machinery can’t physically adapt them
Histone deacetylase (HDAC) enzymes are responsible for removing acetyl groups

Question 37

How can drugs treat diseases caused by epigenetic changes?

Answer 37

Epigenetic changes are reversible
The drugs used are designed to counteract the epigenetic changes that cause the disease
Drugs can stop methylation
HDAC inhibitor drugs
These drugs have to be specific as possible because these changes take place normally in a lot of cells

Question 38

What is epigenetics?

Answer 38

Heritable changes to gene expression
Without changes to the base sequence of DNA