Lecture 1 Genetics (vertical)

Question 1

1. What does the arrow represent on the pedigree?
2. How to represent that the partners were distantly related?
3. 5% of families with breast cancer will have a susceptibility to development of the disorder due to mutations in one of two genes - what are they and where are they located?

Answer 1

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Question 2

Identifying BRCA1/2 mutation carriers - the clinical process

1. Risks are calculated from where?
2. Any woman at a predetermined risk (say 10%) of having a mutation in one of these genes, has them examined for mutations by what?
3. The BRCA1/2 genes are targeted for sequencing - variants are identified by a genetic pathologist and the results are explained by a genetic counsellor.
4. Not everyone who inherits a BRCA1/2 mutation…..

Answer 2

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Question 3

Risk management for BRCA1/2 mutation carriers:

1. Breast
   - when do you get a clinical exam?
   - Mammo from 10y before youngest affected fam member and baseline is at 25 years
   - consideration for _____ mastectomy
2. Ovarian
   - prophylactic what?

Answer 3

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Question 4

If a child with structural heart defect comes in, what do two things do you do first? Then you think whether the problem could be chromosomal

Answer 4

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Question 5

What is the modern way to look for chromosomal imbalance?

Answer 5

A generalised, genome-wide surgery for imbalances: comparative genomic hybridisation (CGH).

Question 6

What if the answer isn’t at chromosomal level? Then what level do you look?

What’s the search space called?

Answer 6

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Question 7

Human genetic variation:

1. Only ____% of the genome is variable
2. Variation lies at what two different levels?
   #1 - ____ regions of genes vary and you have common and _____ variation
   #2 - houses most of variation and more _____ functional effects; difficult to predict and measure

Answer 7

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Question 8

The genomic toolbox:

1. Iterative gene sequencing:
   - what is it and give an example of a gene it can sequence
2. Highly parallel genomic sequencing
   - Panels/families of genes (10-500 pre-selected genes of interest)
   - Genotype signatures - panels of what?
   - Sequencing the entire ____ genome (1% of genome, 21k genes)
   - Sequencing the whole genome

Answer 8

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Question 9

Different diseases have differing genetic architectures - explain that using the graph

• Mendelians are what? (3)
• Common diseases are what? (3)

Answer 9

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Question 10

What about the genetic architecture of obesity? Explain that using a graph?

Answer 10

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Question 11

Back to breast cancer - can genetics genetics help the other 95%?

Answer 11

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