Factors Affecting Gene Expression Flashcards

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1
Q

What is cell differentiation?

A

The process by which a cell becomes specialised for a particular function

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2
Q

What are the ‘housekeeping’ proteins?

A

Proteins involved in the structures common to most cells, e.g. the structural proteins of the membranes and the enzymes involved in cellular respiration

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3
Q

How can scientists measure the level of differentiation that has taken place in cells and work out which genes have been expressed and which have been suppresed?

A

By comparing the different proteins found in different cells

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4
Q

Whaat are gene probes?

A

They allow a particular section of DNA or RNA to be identified due to complementary base pairing

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5
Q

What is DNA - RNA hybridisation?

A

When the gene probe finds the unique sequence of nucleotides on the DNA that make up the gene using a stretch of RNA that has the complementary sequence

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6
Q

What happens when using a gene probe?

A

The DNA from the cells under investigation is isolated and heated gently. This breaks the weak hydrogen bonds holding together the two strands of DNA. Fluorescently - labelled mRNA for the required gene is added - this is the probe. Any DNA-RNA hybridisation that takes place shows that the required gene is present. Tbis hybridisation is pinpointed using the fluorescent label on the mRNA

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7
Q

What two stages does expression of a gene involve?

A

Transcription from DNA to mRNA and translation from mRNA to proteins

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8
Q

What determines the the type of cell and its function in the body?

A

The different proteins present in the cell and the quantities of the different proteins

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9
Q

What is the most common way of controlling gene expression?

A

By switching on and off the transcription of certain genes.

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10
Q

What are transcription factors?

A

Proteins that bind to the DNA in the nucleus and affect the process of transcribing the genetic material

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11
Q

What are promoter sequences?

A

Specific regions on the DNA to which transcription factors bind to stimulate transcription

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12
Q

Where are promoter sequencea usually found?

A

Just above the starting point for transcription upstream of the gene (the 5’ end).

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13
Q

What do some types of transcription factors do and what do others do?

A
  • some transcription factors stimulate the transcription of a region of DNA simply by binding to a DNA promoter sequence, stimulating the start of transcription of that area of DNA
  • Other transcription factors bind to regions known as enhancer sequences and regulate the activity of the DNA by changing the structure of the chromatin making it practically open to RNA polymerase. An open chromatin structure is linked to active gene expression and closed chromatin structures are associated with gene inactivity. The regulatory sites can be at the site of the gene or a considerable distancd away from the gene that they are controlling
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14
Q

What is a way that control over multiple genes is achieved?

A

By a single transcription factor controlling tbe activity of a number of genes. E.g. stimulating the expression of one and repressing another

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15
Q

What is pre-mRNA?

A

The mRNA that is transcribed directly from the DNA before it has been modified?

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16
Q

What are spliceosomes?

A

Enzyme complexes that act on pre-mRNA joining exons together after the removal if the intronss

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17
Q

What are spliceosomes?

A

Enzyme complexes that act on pre-mRNA joining exons together after the removal if the intronss

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18
Q

What do the modifications of pre-mRNA involve?

A

The removal od the introns and in some cases some of the exons too. The exons are then joined together by spliceosomed to produce the mature functional mRNA

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19
Q

What is the process of the spliceosomes joining the exons called?

A

RNA splicing

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20
Q

Why may a genotype produce more proteins than there are genes?

A

The spliceosomes may join the same exons in a variety of ways. As a result a single gene may produce several versions of functional mRNA transcribed from the same sections of DNA. These different versions of mRNA code for different arrangements of amino acids which in turn produce different polypeptide chains and so different proteins. Ultimately this can result in a single gene producing several different phenotypes. These post-transcriptional changes to mRNA lead to more variety in the phenotype than is coded for directly in the genotype

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21
Q

What may happen to a protein after it is synthesised?

A

Further modifications may take place. A protein that is coded for by a gene may remain intact or it may be shortened or lengthened by enzymes to give a variety of other proteins

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22
Q

What does epigenetics study?

A

Genetic control by factors other than the base sequences on the DNA.

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23
Q

Why is RNA splicing a form of epigenetic control?

A

because it changes the mRNA and the proteins produced from the original genetic code

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24
Q

What are three inteacellular systems tgat can interact to control genes?

A
  • DNA methylation
  • histone modification
  • non-coding RNA
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25
Q

What is DNA methylation?

A

The methylation of DNA (addition of a methyl - CH3 group) to a cytosine in the DNA molecule next to a guanine in the DNA chain and prevents the transcription of a new gene

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26
Q

In DNA methylation what is the methyl group added by?

A

A DNA methyltransferase enzyme

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27
Q

What does DNA methylation do?

A

It always silences a gene or a sequence of genes. The methyl group changes the arrangement of the DNA molecule and prevents transcription from taking place. DNA methylation is very important in controlling gene expression

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28
Q

What processes is DNA methylation important in?

A

Embryonic development and X chromosome inactivation. In many adult specialised cells, many genes are silenced by DNA methylation most or all of the time

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29
Q

What is DNA demethylation?

A

Is the removal of the methyl group from methylated DNA enabling genes to become active so they can be transcribed

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30
Q

What are histones?

A

Positively charged proteins

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31
Q

What is chromatin?

A

The DNA/protein complex that makes up chromosomes

32
Q

How is chromatin formed?

A

DNA winds around the histones

33
Q

What is heterochromatin?

A

The densely supercoiled and condensed chromatin where the genes are not availabe to be copied to make proteins

34
Q

What is one way that cells of different types are produced from active chromatin?

A

Active chromatin is more loosely held together, with uncoiled regions of DNA opening up more genes for transcription so that new proteins are made

35
Q

What are two modification processes of histones?

A
  • histone acetylation - an acetyl group (-COCH3) is added to one of the lysines in the histone structure. Adding an acetyl group usually opens up the structure and activates the chromatin, allowing genes in that area to be transcribed. Removing an acetyl group produces heterochromatin again
  • histone methylation - a methyl group is added to a lysine in the histone. Depending on the position of the lysine, methylation may cause inactivation of the DNA or the activation of a region. Methylation is often linked to the silencing of a gene and even whole chromosomes
36
Q

What does a lot of the non-coding RNA (ncRN) seem to do?

A
  • Affect the transcription of the DNA code or modifies the products of transcription. Genes and whole chromosomes have been silenced by ncRNAs
  • involved in chromatin modification, where it acts on the histones to make areas of the DNA available or unavailable for transcription
37
Q

How is ncRNA involved in the silencing of one X chromosome in female mammals?

A

It is largely due to the presence of an ncRNA called X-inactive specific transcript (Xist), which is produced by the active Xist gene on the inactive chromosome. The ncRNA coats one of the X chromosomes in female cells and deactivates it. The chromosome supercoils and condenses to form the stable inactive Barr body

38
Q

What are epigenetic modifications often the result of?

A

DNA methylation or demthylation or of histone modification

39
Q

What does the term totipotent describe?

A

An undifferentiated cell that can form any one of the different types of cell needed for an entire new organism

40
Q

What is cleavage?

A

It involves a special type of mitosis in which cells divide repeatedly without the normal interphase for growth between divisions. The result of cleavage is a small mass of identical undifferentiated cells forming a hollow sphere known as the blastocyst. It takes place as the zygote is moved along the oviduct towards the uterus

41
Q

What are embryonic stem cells?

A

The undifferentiated cells of the early human embryo with the potential to develop into many different types of specialised cells

42
Q

What are pluripotent embryonic stem cells?

A

It describes an undifferentiated cell that can form most of the cell types needed for an entire new organism. However is cannot form tissue such as the placenta. They are the cells in the inner layer of the blastocyst

43
Q

By what time will the cells in an embryo become sufficiently specialised and what are the stages of this?

A

First the pluripotent stem cells becone more specialised as the embryo develops forming e.g. blood stem cells which will then give rise to blood cells. By about 3 months of pregnancy the cells have become sufficiently specialised that when they divide they only form more of the same type of cell

44
Q

What is a rich store of pluripotent stem cells?

A

The blood that drains from the placenta and umbillical cord after birth

45
Q

What are somatic stem cells/ adult stem cells?

A

Undifferentiated cells found among the normal differentiated cells in a tissue or organ that can differentiate when needed to produce any one of the major cell types found in that particular tissue or organ

46
Q

What does the term multipotent describe?

A

A cell that can form a very limited range of differentiated cells within a mature organism

47
Q

What is cell determination closely linked to?

A

The position of the cells in the embryo

48
Q

What is the most common way of controlling gene expressio ?

A

By switching on and off the transcription of certain genes

49
Q

What is it that results in the different characteristics of fully differentiated mature cells?

A

The combination of the particular genes that are activated or silenced

50
Q

What happens as the different types of globin chains change in the 40 weeks of pregnancy before becoming haemoglobin?

A

The genes for different proteins get switched on and off. Also the genes are activated in different tissues as the development progresses. Globin production moves from the yolk sac in the embryo to the liver in the fetus and then the spleen with the genes in the one marrow taking over almost completely by the time of birth

51
Q

What happens as the different types of globin chains change in the 40 weeks of pregnancy before becoming haemoglobin?

A

The genes for different proteins get switched on and off. Also the genes are activated in different tissues as the development progresses. Globin production moves from the yolk sac in the embryo to the liver in the fetus and then the spleen with the genes in the one marrow taking over almost completely by the time of birth

52
Q

What epigentic control mechanisms have scientists found evidence of that are linked to the different haemoglobin chains being coded for?

A
  • histone acetylation activates the gamma globin gene in the fetus
  • DNA methylation appears to play a major role in silencing the fetal gamma globin genes just before and after birth
  • histone methylation seems to play a complementary role to DNA methylation in silencing the fetal gamma globin
  • ncRNAs have been associated with the process but scientists are not yet sure what they do
  • a number of transcription factors have been shown to be key in the switch to the production of beta globin in the spleen and bone marrow as the fetus approaches full term
53
Q

How has a trachea been produced using adult stem cells?

A

Stem cells from a patient are seeded onto a framework which may be collagen based and from a donor or completelt synthetic. The stem cells grow to form the required cells and the new trachea can be returned to the patient with no risk of rejection

54
Q

What is therapeutic cloning?

A

An experimental technique used to produce embryonic stem cells from an adult cell donor

55
Q

How does therapeautic cloning take place?

A
  • first remove the nucleus from one of the patients normal body cells
  • next transfer it to a human ovum which has had it’s original nucleus removed
  • a mild electric shock is used to fuse the nucleus with the new cell and trigger development
  • the newly formed pre-embryo stem cell starts to develop and divide, producing a collection of embryonic stem cells with the same genetic information as the patient
  • this embryo is a source of stem cells with genetic markers that perfectly match the patient
  • stem cells are harvested from the embryo which is destroyed in the process.
  • the embryonic stem cells can then be cultured in a suitable environment so that they differentiate into the required tissue
  • these tissue cells can then be transferred to tbe patient where they can do their job without the risk of the immune system rejecting them
  • the adult stem cell nucleus would need to be genetically modified before being added to the empty ovum, otherwise the cultured stem cells would carry the genetic mutation that caused the problem in the first place
56
Q

What is a problem that relates to the use of all kinds of stem cells?

A

No one is quite sure how the genes in cells are switched on and off to form particular types of tissue

57
Q

What are the risks associated with stem cell therapy?

A

There are concerns that stem cells could cause the development of cancers in the body.

58
Q

What are some of the potential advantages of stem celk therapy?

A

At the moment there are no cures for many of the conditions that stem cell therapy might solve. The ability to produce tailor-made cells to take over the function of damaged ones would revolutionize medicine

59
Q

What’s the problem with organ transplants?

A

Glycoproteins on the surface of your cell membranes act as part of your cell recognition system. You immune system recognises your own cells and different cells and destroys the non-self cells. Therefore your immune system could attack a transplanted organ. After a transplant people have to take immunosupressant drugs for the rest of their lives and this will put them at a higher risk of infectious diseases

60
Q

What is an advantage of using embyonic stem cell therapy?

A

It could avoid the risk of rejection

61
Q

What are insuced pluripotent stem cells (iPS cells)?

A

Adult cells that have been reprogrammed by the introduction of new genes to become pluripotent again

62
Q

What are the genes necessary to produce pluripotent stem cells and what are the genes that increase the likelihood and efficiency of producing pluripotency in adult cells?

A

Necessary: Oct3 or Oct4 and one of the Sox family of genes

Increasing likelihood: Myc family and Klf family

63
Q

What are the benefits of iPS cells?

A

It overcomes the ethical objections to using embryonic tissue, even embryos specifically created as a source of stem cells. There is also no risk of rejection if cells from an individual are used to provide their own stem cells

64
Q

What are the problems with iPS cells?

A

It is hard to persuade them to become pluripotent and making then differentiate is even more difficult. Furthermire we still do not know how well and for how long they will behave as pluripotent stem cells. They also show a tendency to become cancerous very quickly. This is because Klf4 and c-Myc are oncogenes, genes that are particularly associated with cancer development

65
Q

What is Parkinsons disease?

A

A brain disorder. Nerve cells in the brain that produce dopamine (dopamine neurones) stop working and are lost. As dopamine levels fall people develop uncontrollable tremors in their hands and body, their body becomes rigid and eventually they cannot move normally at all.

66
Q

How did scientists help parkinsons in rats using embryonic stem cells?

A

Scientists got mouse embryonic stem cells to form dopamine neurones. These cells were implanted into the brain of rats that had the symptoms of Parkinsons disease. The cells grew and released dopamine and the ability of the rats to control their movement improved

67
Q

What so scientists think offers the best current hope of an effective long term treatment for Parkinsons disease?

A

Pluripotent stem cells

68
Q

What is type 1 diabetes?

A

The glucose sensitive insulin secreting islet of Langerhans cells in the pancreas are destroyed or stop making insulin so the blood glucose concentration is uncontrolled. This can be very serious or even fatal

69
Q

What is currently used to treat type 1 diabetes?

A

Insulin injections and monitoring food intake and blood glucose concentration levels

70
Q

How have scientists treated type 1 diabetes in mice using embryonic stem cells?

A

They have gotten some mouse embryonic stem cells to form a group of cells that look and wok just like insulin producing tissue. Some of these cells were transplanted into mice with diabetes where they produced a rise in the blood concentration of insulin and improved control of blood glucose

71
Q

What was the breakthrough by Harvad university in 2014 to do with type 1 diabetes?

A

Starting with human embryonic stem cells, they have developed mature human glucose-sensitive insulin-producing beta cells in the large quantities needed to use them in patients. The cells are now being trialled in animals with diabetes

72
Q

What are areas in which scientists feel like pluripotent or embryonic stem cells could give real therapeutic value?

A
  • treating Parkinsons disease
  • treating type 1 diabetes
  • transplanting them to replace damaged nerves
  • growing organs for transplants
73
Q

What are the four ethical principles in science?

A
  • respect for autonomy. Respect individuals by not performing procedures without consent
  • Beneficience. The aim of doing good by giving medicine to relieve suffering ect.
  • non-maleficence. To do no harm
  • justice. Treat everyone equally and share resources fairly so as to avoid discrimination
74
Q

Why do people feel that ethically using stem cells from embryos is okay?

A
  • the vast majority of human embryos never make it beyond development to form living babies so the argument for using a small number of early embryos is considered acceptable in this context
  • once tissue lines from a relitavely small number of willingly donated embryos are established the need to use further embryos will be reduced
  • adult stem cells do not offer a good alternative because they are more limited in their scope for forming new and different tissues
75
Q

Why do some people feel that the use of embryonic stem tissue is wrong and an abuse of human rights?

A
  • Some objectors feel that every early human embryo has the potential to become a living human being and so should be afforded the same rights as a fully grown adult
  • others have strong religious convictions that using embryos is killing and therefore wrong
  • many people feel that the use of adult stem cells offers an exciting and acceptable alternative to embryonic stem cells
76
Q

Why are people ethically for therapeutic cloning?

A

As the embryos are not created to develop into a new human being, simply to provide embryonic stem cells.

77
Q

Why do people morally object to the use of therapeutic cloning?

A
  • people fear that if the cloning is allowed for therapeutic purposes it could easily be taken further with the cloned embryos implanted into a uterus to produce a cloned baby
  • even if the embryo used as a source of stem cells it is still an embryo and many people have the same ethical or religious objectjons to using these for research as they do to the use of any other embryos