Midterm 2 - Notes 5 (Part 1) Flashcards

1
Q

Cancer critical genes

A

Gene that contribute to cancer formation when mutated

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2
Q

What do individual cancers have?

A

Individual mutations

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3
Q

What does an alteration in a given gene that contribute to cancer depend on? (4)

A
  1. Type of mutation
  2. Cell type
  3. Interaction with other mutated gene products
  4. Differentiation status
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4
Q

Identification of mutations in a given cancer is starting point for what 3 things?

A
  1. Identification of the mutation in cancer
  2. Understanding cancers on a molecular level
  3. Targets for diagnosis and drug development or other treatments
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5
Q

What is the benefit of identifying the mutation in cancer?

A

It can be cataloged to see what went wrong, how it started and identify how to prevent them
- its the holy grail

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6
Q

Why is it better to used short sequences when comparing genomes?

A

It makes it easier

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7
Q

What can you conclude if the reference genome is different than the normal genome and not from higher up?

A

That is it a somatic mutation and not inherited

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8
Q

What was detected in the cancer genome sequencing experiment?

A

Types of alterations in both coding and non-coding regions

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9
Q

What can you discover information about when you compare cancer with normal genomes of the same individual?

A

You can identify the somatic mutation information

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10
Q

What does it mean if a sequence map contains no reads?

A

We can conclude there was a homo deletion in the tumour DNA

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11
Q

What does it mean if a sequence map contains a few reads?

A

We can conclude there was a hetero deletion in the tumour DNA

  • will get 1/2 the amount of reads
  • more than one copy leads to genome duplication
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12
Q

What can you conclude from jumping from chromosome 1 to chromosome 5?

A

That there was some sort of gene translocation that took place

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13
Q

What was being dealt with in the first attempt of cancer genome sequencing?

A

Highly malignant leukemia

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14
Q

What are 3 things they found in the case study involving cancer genome sequencing?

A
  1. No large alterations
    - chromosomes look fairly normal
  2. Typical symptoms
  3. Used both tumour (test) and skin (control) samples for sequencing
    - used this to identify the inherited gene
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15
Q

What kind of sequencing did they use in the caner genome sequencing experiment?

A

Illumina sequencing

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16
Q

What happened in the tumour sequencing for the experiment? (2)

A
  1. Used short reads

2. Did quality filtering

17
Q

What did quality filtering allow?

A

Detection of heterozygous mutations

18
Q

What happened in the skin (control) sequencing for the experiment? (2)

A
  1. Expected them to be similar to the reference

2. Didn’t need as much and wanted to save money

19
Q

What was the 2nd experiment sequencing mapping and variant calling about?

A

It was a proof of concept experiment

- needed to prove that it did work

20
Q

What did they do in the sequencing mapping and variant calling experiment? (3)

A
  1. Aligned sequences to human reference genome
    - 3.8 million single nucleotide differences
    - could be SNP or SNV
  2. Compared it to 2 other individual human genomes
    - number of SNP variants to hg18
    - used sanger and illumina sequencing
  3. Used SNP array to determine variants
21
Q

What human genome did they use as a reference in the sequencing mapping and variant calling experiment?

A

hg 18

- human genome 18

22
Q

SNP

A

Single nucleotide polymorphism

- inherited differences

23
Q

SNV

A

Single nucleotide tumour variants

- somatic differences (but sometimes can also be inherited)

24
Q

What was the final conclusion about the sequencing mapping and variant calling experiment?

A

Was that yes we can use it to determine whole genome sequencing

25
What did a high quality data filter do?
Reduced the number of SNPs | - different though from human genome sequencing
26
Passenger mutations
Are mutations that do not provide a growth advantage to cancer - do not contribute to cancer formation
27
What is the type of mutation that is dealt with the most in this experiment?
Passenger mutations
28
What are the candidate mutations?
Candidates for being somatic mutations | - higher than expected
29
What does it mean that the candidates for somatic mutations were higher then expected?
That the tumour accumulated 10s of thousands of somatic mutations on its way to becoming cancerous
30
What did they expect in this experiment?
Most were passenger mutations
31
What did they focus on?
Protein coding gene regions
32
SNVs filtered out due to what 3 things?
1. Present in the germ line of other individuals - unlikely this caused it to be cancerous 2. In non-coding regions - introns 3. Synonymous
33
Synonymous
Silent mutations where codon changes but still produced the same amino acid protein - unlikely to change the protein function
34
What 2 things did they use to validate SNVs?
1. Targeted PCR | 2. Sanger sequencing
35
What did they find a large majority of?
False positives | - which created a high error rate
36
Was the proof of concept successful?
Yes