8.1 and 8.2

Question 1

What is a gene mutation?

Answer 1

A change in the base sequence of DNA which can arise spontaneously during DNA replication

Question 2

What is a mutagenic agent?

Answer 2

Factor that increases the rate of mutation e.g UV or alpha particles

Question 3

Explain how a gene mutation can lead to the production of a non functional protein or enzyme:

Answer 3

Changes sequence of base triplets in DNA so changes sequence of codons on mRNA
So changes sequence of amino acids in the encoded polypeptide
So changes position of hydrogen/ionic/disulfide bonds
So changes tertiary structure
Enzymes- active site altered so substrates can’t bind and E-S complexes can’t form

Question 4

Describe the 6 different types of mutation:

Answer 4

Substitution- a base is replaced by a different base in DNA
Addition- one or more bases are added to the DNA sequence
Deletion- one or more bases are lost from the DNA base sequence
Duplication- a sequence of DNA bases is repeated
Inversion- a sequence of DNA bases detaches from the DNA sequence and then rejoins at same position in reverse order
Translocation- a sequence of bases detaches and is inserted at a different location within the same or a different chromosome

Question 5

Why do not all gene mutations affect the order of amino acids?

Answer 5

Some substitutions change only one triplet code which could still code for the same amino acid as genetic code is degenerate
Some occur in introns which do not code for amino acids

Question 6

Explain why a change in amino acid sequence is not always harmful:

Answer 6

May not change tertiary structure of protein
May positively change the properties of the protein, giving organism a selective advantage

Question 7

What is meant by a frameshift?

Answer 7

Occurs when mutations change the number of nucleotides/bases by a number not divisible by 3
Shifts the ways the genetic code is read from all the DNA triplets downstream from the mutation change

Question 8

Explain how mutations lead to production of shorter polypeptides:

Answer 8

Deletion or translocation so codons missing so amino acids missing
Substitution, addition, deletion, duplication, inversion and translocation could cause premature stop codon so amino acids missing at end of polypeptide

Question 9

What are stem cells?

Answer 9

Undifferentiated/unspecialised cells capable of
1. Dividing by mitosis to replace themselves indefinitely
2. Differentiating into other types of specialised cells

Question 10

Describe how stem cells become specialised during development:

Answer 10

Stimuli lead to activation of some genes (due to transcription factors)
So mRNA is transcribed only from these genes and then translated to form proteins
These proteins modify cells permanently and determine cell structure/function

Question 11

Describe totipotent cells:

Answer 11

Occur for a limited time in early mammalian embryos
Can divide and differentiate into any type of body cells

Question 12

Describe pluripotent cells:

Answer 12

Found in mammalian embryos after first few cell divisions
Can divide and differentiate into most cell types (but not placental cells)

Question 13

Describe multipotent cells:

Answer 13

Found in mature mammals
Can divide and differentiate into a limited number of cell types (e.g bone marrow cells can divide into different blood cells)

Question 14

Describe unipotent cells:

Answer 14

Found in mature mammals
Can divide and differentiate into just one type of cell (e.g. cardiomyocytes)

Question 15

Explain how stem cells can be used in treatment of humans:

Answer 15

Transplanted into patients to divide in unlimited numbers
Then differentiate into required healthy cells

Question 16

Explain how induced pluripotent stem cells (iPS) are produced:

Answer 16

Obtain adult somatic cells from patient
Add specific protein transcription factors associated with pluripotency to cells so they express genes associated with pluripotency
-Transcription factors attach to promoter regions of DNA, stimulating or inhibiting transcription
Culture cells to allow them to divide by mitosis

Question 17

Evaluate the use of stem cells in treating human disorders:

Answer 17

Pro:
Can divide/differentiate into required healthy cells so could relieve human suffering by saving lives and improving quality of lives
Embryos are often left over from IVF and would otherwise be destroyed
iPS unlikely to be rejected by patient’s immune system as made with own cells
iPS cells can be made without destruction of embryo and adult can give permission

Against:
Ethical issues with embryonic stem cells as destruction of ‘potential life’
Immune system could reject cells and immunosuppressant drugs required
Cells could divide out of control, leading to tumours/cancer

Question 18

What are transcription factors?

Answer 18

Proteins which regulate transcription of specific target genes in eukaryotes
By binding to a specific DNA base sequence on a promoter region

Question 19

Describe how transcription can be regulated using transcription factors:

Answer 19

Transcription factors move from cytoplasm to nucleus
Bind to DNA at specific DNA base sequence on a promoter region
This stimulates or inhibits transcription of target genes by helping or preventing RNA polymerase binding

Question 20

How does oestrogen affect transcription?

Answer 20

Oestrogen is a lipid soluble hormone so diffuses into cell across the phospholipid bilayer
In cytoplasm, oestrogen binds to its receptor, an inactive transcription factor, forming an oestrogen-receptor complex
This changes the shape of the inactive transcription factor, forming an active transcription factor
The complex diffuses from the cytoplasm to the nucleus
Then binds to a specific DNA base sequence on the promoter region of the target gene
Stimulating transcription of target genes forming mRNA by helping RNA polymerase bind

Question 21

Why does oestrogen only affect target cells?

Answer 21

Other cells do not have oestrogen receptors

Question 22

What is meant by epigenetics?

Answer 22

Heritable changes in gene function/expression without changes to the base sequence of DNA
Caused by changes in the environment

Question 23

What is meant by epigenome?

Answer 23

All chemical modifications of DNA and histone proteins- methyl groups on DNA and acetyl groups on histones

Question 24

Summarise the epigenetic control of gene expression in eukaryotes:

Answer 24

Increased methylation of DNA inhibits transcription, whilst decreased methylation of DNA allows transcription

Decreased acetylation of histones inhibits transcription, whilst increased methylation of histones allows transcription

Question 25

How does methylation inhibit transcription?

Answer 25

Increased methylation of DNA- methyl groups added to cytosine bases in DNA SO nucleosomes pack more tightly together together Preventing transcription factors and RNA polymerase binding to promoter

Question 26

Explain how acetylation inhibits transcription:

Answer 26

Decreased acetylation of histones increases positive charge of histones So histones bind DNA more tightly Preventing transcription factors and RNA polymerase binding to promoter

Question 27

Explain the relevance of epigenetics on disease development and treatment:

Answer 27

Environmental changes can lead to epigenetic changes These can stimulate/inhibit expression of certain genes that can lead to disease development Diagnostic tests can be developed to detect these epigenetic changes before symptoms present Drugs can be developed to reverse these epigenetic changes

Question 28

What is RNAi?

Answer 28

Inhibition of translation of mRNA produced from from target genes, by RNA molecules (siRNA/miRNA) This inhibits expression of a target gene

Question 29

Describe the regulation of translation by RNAi:

Answer 29

siRNA or miRNA is incorporated into a protein, forming an RNA-induced silencing complex (RISC) -siRNA synthesised as double stranded RNA with one strand being incorporated -miRNA synthesised as double stranded hairpin bend of RNA, with both strands being incorporated Single stranded miRNA/siRNA within RISC binds to target mRNA with a complementary base sequences This leads to hydrolysis of mRNA into fragments which are then degraded OR prevents ribosomes binding Reducing/preventing translation of target mRNA

Question 30

How do tumours and cancers form?

Answer 30

Mutations in DNA/genes controlling mitosis leads to uncontrolled cell division Tumour formed if this results in mass of abnormal cells -Malignant= cancerous, spreads by metastasis -Benign= non-cancerous

Question 31

Compare benign and malignant tumors

Answer 31

Benign: Grow slowly Well differentiated/specialised Normal/regular nuclei Well defined borders and often surrounded by capsule Don't spread by metastasis Can be removed by surgery and rarely return Malignant: Grow faster Poorly differentiated/specialised Irregular, larger/darker nuclei Poorly defined borders and not encapsulated so invade surrounding tissues Spread by metastasis Surgery+chemo/radiotherapy but often return

Question 32

Describe the function of tumour suppressor gene:

Answer 32

Code for proteins that: Inhibit/slow cell cycle OR cause self destruction of potential tumour cells

Question 33

Explain the role of tumour suppressor genes in the development of tumours:

Answer 33

Mutation in base sequence- production of non functional proteins Decreased histone acetylation OR increased DNA methylation so prevents production of protein Lead to uncontrolled cell division

Question 34

Describe the function of (proto-)oncogenes:

Answer 34

Code for proteins that stimulate cell division

Question 35

Explain the role of oncogenes in development of tumours:

Answer 35

Mutation in DNA base sequence- overproduction of protein or permanently activated protein Decreased DNA methylation or increased histone acetylation increases production of protein Both lead to uncontrolled cell division

Question 36

Suggest why tumours require mutations in both alleles of tumour suppressor gene but only one allele of an oncogene:

Answer 36

One functional allele of a tumour suppressor gene can produce enough protein to slow the cell cycle OR cause self destruction of potential tumour cells One mutated oncogene allele can produce enough protein to lead to rapid/uncontrolled cell division

Question 37

Explain the role of epigenetics in cancer treatment:

Answer 37

Increasing DNA methylation or decreasing histone acetylation of oncogene to inhibit transcription Decreasing DNA methylation or increasing histone acetylation of tumour suppressor gene to stimulate transcription

Question 38

Explain the role of increase oestrogen concentrations in the development of some breast cancers:

Answer 38

Some breast cancers have oestrogen receptors which are inactive transcription factors If oestrogen conc. is increased, more oestrogen binds to oestrogen receptors, forming more oestrogen-receptor complexes which are active transcription factors These bind to promoter regions of genes that code for proteins stimulating cell division This increases transcription/expression of these genes, increasing the rate of cell division

Question 39

Suggest how drugs that have a similar structure to oestrogen help treat oestrogen receptor-positive breast cancers:

Answer 39

Drygs bind to oestrogen receptors, preventing binding of oestrogen So no/fewer transcription factors bind to promoter regions of genes that stimulate cell cycle