The human genome and disease

Question 1

What are mutations?

Answer 1

Permanent changes to the DNA sequence

Can be inherited or acquired

Question 2

What are germline mutations?

Answer 2

Mutations that are inherited and are passed on via gametes

Question 3

What are somatic mutations?

Answer 3

Mutations can also be acquired by somatic cells if DNA gets damaged or is copied incorrectly.
- These are not passed on to the next generation

Question 4

What do mutations do?

Answer 4

They are the driving force for evolution

• Mutations can have a beneficial effect, no effect, or a deleterious (damaging or harmful) effect on the organism.
• The vast majority have no effects at all

Question 5

What can the outcome of a mutation depend on?

Answer 5

• Environmental factors e.g. diet and exposure to toxins

- Other genes

Question 6

What are to two ways to classify a mutation?

Answer 6

Dominant vs recessive
or
Loss of function vs gain of function

Question 7

Are humans diploid or haploid? What does this mean?

Answer 7

Diploid

This means they have two copies of each of their genes (one maternal, one paternal)

Question 8

What is a dominant mutation?

Answer 8

A dominant mutation is one that causes a phenotype when heterozygous

Question 9

What is a recessive mutation?

Answer 9

A recessive mutation is one that causes a phenotype when homozygous

Question 10

What can a mutation do to a gene to cause the phenotype?

Answer 10

For a mutation (allele) to have a phenotype, it must affect the function of a gene
- A mutation might break a gene to cause it to not work as well as before or not at all.

Question 11

What is a “loss of function” mutation?

Answer 11

Loss of function mutations are often recessive, because a normal copy of the gene exists on the other chromosome which can replace the lost function.

• Causes the gene to break or to not work as well as normal

Question 12

What is a “gain of function” mutation?

Answer 12

Gain of function mutations are often dominant, because having an allele that works too well or does something novel, will not be replaced by the normal copy of the gene.

• Causes a gene to work too well, or do something unexpected

Question 13

What is an example of a monogenic disease?

Answer 13

• Haemophilia A and B
• Cystic fibrosis
• Huntington’s

Question 14

What are polygenic disorders?

Answer 14

• -> Involves several genes acting together or environmental factors with genes
• -> Some examples are diabetes, rheumatoid arthritis, bipolar disorder
• -> indentifying genes with polygenetic disorders is very hard

Question 15

Are genetic disorders probabilistic or deterministic and why?

Answer 15

They are mostly probabilistic as such disease come about through a combination of variants and the environment
–> Having disease related variation does not mean you will 100% get the disease

Question 16

What is Haemorphilia?

Answer 16

A X-linked recessive disease

• -> Caused by a “loss of function” allele
• -> Males are more likely to get this
• -> Sons of women carriers have 50% of getting the disease

Question 17

What is Huntington’s?

Answer 17

• -> Autosomal dominant

- -> Repeat expansion of CAG on chromosome 4

Question 18

What is Cystic fibrosis?

Answer 18

• -> Autosomal recessive disease

- -> Mutation in CTFR gene, most common is deletion of DeltaF508