Module

Question 1

What is a nucleosome?

Answer 1

Unit of chromatin- DNA wound around 8 histone

proteins 1.65 times

Question 2

What charge are histones?

Answer 2

positive

Question 3

What charge is DNA and why?

Answer 3

negative, due to the phosphate groups

Question 4

What is the function of H1?

Answer 4

stabilising chromatin in higher order chromosomal structures e.g. 30 nm fibres of chromatin

Question 5

Name 2 mechanisms to make chromatin more accessible:

Answer 5

• Histone modifications e.g. HATs

- chromatin remodelling complexes

Question 6

What are HATs and HDACs?

Answer 6

• Histone Acetyl Transferases

- Histone Deacetylases

Question 7

What do HATs do?

Answer 7

transfer acetyl groups to histones,associated with euchromatin, linked to increased gene expression

Question 8

What do HDACs do?

Answer 8

remove acetyl groups from histones, allow histones to wrap more tightly, less accessible

Question 9

What are the 3 stages of Transcription?

Answer 9

Initiation
Elongation
Termination

Question 10

What does RNA Pol I transcribe?

Answer 10

rRNA

Question 11

What does RNA Pol II transcribe?

Answer 11

mRNA

Question 12

What does RNA Pol III transcribe?

Answer 12

tRNA

Question 13

What happens in transcription initiation?

Answer 13

• RNA pol and transcription factors bind to promoter
• form a closed pre-initiation complex
• complex opening separates 2 DNA strands and moves template strand to active site of RNA Pol
• Abortive synthesis
• Promoter escape

Question 14

What happens in transcription elongation?

Answer 14

• RNA pol travels along template DNA strand in 5’ to 3”
• Synthesises RNA strand 5’ to 3’
• Transcription bubble

Question 15

In Transcription, what 2 sequences is the cleavage site found between?

Answer 15

AAUAAA - upstream

GU- rich - Downstream

Question 16

How is transcription terminated when the cleavage sequences have been transcribed?

Answer 16

• CPSF binds to AAUAAA
• CstF binds to GU-rich
• Forms protein complex
• CPSF cleaves downstream of AAUAAA site
• Poly(A) polymerase adds a 3’ polyA tail

Question 17

List 3 aims of the 100,000 genomes project:

Answer 17

• Increase understanding of genetic variants -> new treatments
• Bring about personalised medicine
• Greater understanding of genomic medicine benefits

Question 18

What are the aims of the gnoMAD project?

Answer 18

• Bring together exome and genome sequencing data from large scale sequencing projects
• Summarise data for wider scientific community

Question 19

What are the aims of the EXAC project?

Answer 19

To create a browser to display large population datasets of genetic variation and display gene variation

Question 20

What Biochemical evidence shows that the non-coding

genome is important?

Answer 20

• Pervasive Transcription

- Functional genomic elements

Question 21

What Genetic Evidence shows that the non-coding genome is important?

Answer 21

• GWAS
• Non-coding mutations -> mendelian disease
• higher non-coding conservation across mammalian evolution

Question 22

What is a silencer?

Answer 22

combination of short DNA sequence elements that suppress transcription of a gene

Question 23

What is an insulator?

Answer 23

DNA element that acts as a barrier or a blocker of enhancers

Question 24

What is an enhancer?

Answer 24

short region of DNA that can be bound by activators to increase the likelihood of a gene being transcribed

Question 25

How do enhancers increase gene expression?

Answer 25

promoter-enhancer loops | allow transfer of regulatory elements (TF's) over a long distance

Question 26

Give 4 reasons why it is hard to identify enhancers:

Answer 26

- found at various distances from target promoter - found/regulate upstream and downstream genes - scattered across 98% of the genome - many enhancers not evolutionarily conserved

Question 27

What is gene panel sequencing?

Answer 27

targeted sequencing to detect changes in a selected panel of genes known to cause the phenotype

Question 28

What is Clinical Exome Sequencing?

Answer 28

targeted sequencing of exons of known disease genes

Question 29

What is Whole Exome Sequencing?

Answer 29

sequencing of all exons of all genes

Question 30

How many disease causing variants are found within Exons?

Answer 30

>85%

Question 31

What are the 2 Purine bases?

Answer 31

A | G

Question 32

What are the 2 Pyramidine bases?

Answer 32

T | C

Question 33

What type of mutation are 'point mutations'?

Answer 33

Base Substitution

Question 34

What are Transition point mutations?

Answer 34

purine substituted for another purine | pyramidine substituted for another pyramidine

Question 35

What are Transversion point mutations?

Answer 35

purine substituted to pyramidine (vice versa)

Question 36

What is a silent mutation?

Answer 36

mutation that results in a synonymous codon | amino acid sequence stays the same

Question 37

What is a missense mutation?

Answer 37

base substitution resulting in a different codon

Question 38

What are the 2 types of missense mutations?

Answer 38

conservative (similar structure+function) | non-conservative (different structure+properties)

Question 39

What is a nonsense mutation?

Answer 39

base substitution resulting in a stop codon

Question 40

What are deletions?

Answer 40

deletion of one or more base pairs deleted from DNA sequence | causes altered translational frame

Question 41

What are insertions?

Answer 41

insertions of additional base pairs, if it's not a multiple of 3 then causes frameshift

Question 42

What are INDEL mutations?

Answer 42

length difference between 2 alleles and can't be known if it's due to an Insertion or Deletion

Question 43

How long is the mitochondrial genome?

Answer 43

16,569 bp's

Question 44

List 3 features of mtDNA?

Answer 44

- double stranded - circular - encodes 37 genes

Question 45

what is the mutation rate in mtDNA?

Answer 45

1/33 generations

Question 46

What is Heteroplasmy?

Answer 46

The presence of more than one organellar genome within a cell/individual

Question 47

What are the risks of mitochondrial transfer procedures?

Answer 47

- mtDNA carryover - technicality of procedure - operator dependent - virsuses used (karyoplast removal)

Question 48

What are the + and - of Polar body mitochondrial transfers?

Answer 48

+ easier to obtain polar bodies + simple procedure-> micropipette + lower mtDNA carryover - more invasive

Question 49

What ae the relative risks of mTDNA carryover in mitochondrial transfer procedures?

Answer 49

PB1T

Question 50

What is linkage disequilibrium?

Answer 50

The non-random association of alleles at different lociu

Question 51

How can you tell when linkage disequilibrium has occurred?

Answer 51

When 2 alleles are inherited together more often than you'd expect by chance

Question 52

What are 3 characteristics of mendelian disorders?

Answer 52

- Rare - Specific pattern of inheritance - Caused by pathogenic variant

Question 53

List 6 limitations of GWAS studies?

Answer 53

- Large sample size needed - Effect sizes are small - Causal pathway not always determined - SNPs aren't responsible for all variation e.g. CNVs - Limited ethnic studies - Pleiotropy common (variants associated with multiple traits)

Question 54

What is Y chromosomal testing useful for?

Answer 54

for ancestry DNA testing in men

Question 55

What is mitochondrial DNA testing useful for?

Answer 55

determining maternal lineage

Question 56

What are Short Tandem Repeats?

Answer 56

small sequences of the genome that are repetitive and relatively spaced out. Primer site son wither side are the same but no. of repeats between them varies

Question 57

what characteristic of mtDNA makes it ideal for studying relationships between individuals?

Answer 57

Hypervariable region DNA lasts longer - double membrane Constant mutation rate

Question 58

List 4 uses of autosomal testing:

Answer 58

- paternity - Relationship e.g. siblings - DNA fingerprint test - Inherited Disease

Question 59

In genetic testing, what do 12-18 markers show?

Answer 59

proves non-relationship

Question 60

In genetic testing, what do 23-26 markers show?

Answer 60

non-relationship

Question 61

In genetic testing, what do 37-43 markers show?

Answer 61

family markers become clean (e.g. cousins, 2nd cousins)

Question 62

In genetic testing, what do 67 markers show?

Answer 62

perfect matches-> related

Question 63

List 4 disadvantages of DTC Genetic Testing?

Answer 63

- false positives are common - upsetting results - little oversight/regulation of companies (privacy) - Cause decisions based on incorrect info

Question 64

List 4 advantages of DTC Genetic Testing?

Answer 64

+ promotes awareness of disease (better choices) + personalised health info + cheap + further medical genomics research

Question 65

What percentage of cancer is sporadic?

Answer 65

80-90% (somatic mutations)

Question 66

What percentage of cancer is hereditary?

Answer 66

5-10% (germline mutations)

Question 67

What are driver mutations in cancer?

Answer 67

changes to a gene that drive cancer mutation

Question 68

What are passenger mutations in cancer?

Answer 68

Mutations that don't do anything to affect the cancer phenotype

Question 69

In cancer, what can RT-qPCR be used for?

Answer 69

- Diagnosis + monitoring response to treatment of CML | - Recurrence risk in breast cancer

Question 70

What is OncotypeDX?

Answer 70

Genomic test that analyzes the activity of a group of genes that can affect how a cancer is likely to behave and respond to treatment