L-24

Question 1

What is a mutation?

Answer 1

Mutations are permanent changes to the base sequence of DNA that can be inherited or acquired.

Question 2

What is the name for inherited mutations?

Answer 2

Germline mutations

Question 3

Are somatic mutations passed on to the next generation?

Answer 3

No

Question 4

What effect does the vast majority of mutations have?

Answer 4

None

Question 5

What can the outcome of a mutation depend on besides the genome?

Answer 5

• environmental effects

- genetic background

Question 6

How do we classify mutations?

Answer 6

• dominant vs recessive

- loss of function vs gain of function

Question 7

What does a loss of function mutation do?

Answer 7

Breaks a gene to cause it not to work as well as normal, or not at all

Question 8

Are loss of function mutations usually dominant or recessive?

Answer 8

Recessive

Question 9

What do gain of function mutations do?

Answer 9

Cause a gene to work too well , or do something unexpected

Question 10

Are gain of function mutations usually dominant or recessive?

Answer 10

Dominant

Question 11

What are monogenic diseases?

Answer 11

Mutations controlled by a singular gene

Question 12

What is Haemophilia?

Answer 12

A disorder of blood clotting

Question 13

Which is the most common version of haemophilia?

Answer 13

A

Question 14

What proportion of males worldwide have haemophilia A?

Answer 14

1/5000

Question 15

What is haemophilia A a result of?

Answer 15

Imparted or absent clotting factor VIII

Question 16

What are the clinical differences between haemophilia A and B?

Answer 16

There are none

Question 17

What is Haemophilia B a result of?

Answer 17

Impaired or absent clotting factor XI

Question 18

What are the risks of haemophilia if left untreated?

Answer 18

Death from uncontrolled bleeding

Question 19

What is the treatment of haemophilia?

Answer 19

Intravenous infusion of missing proteins

Question 20

What is mutation is haemophilia A mostly caused by?

Answer 20

Inversion mutations on the factor VIII gene of the X chromosome

Question 21

How are the haemophilia mutations classified?

Answer 21

loss of function X-linked recessive

Question 22

What percentage of haemophilia cases have no family history?

Answer 22

30%

Question 23

What are the symptoms of Huntingtons disease?

Answer 23

• progressive tremor
• involuntary movements
• neurodegeneration

Question 24

What is the usual age of onset of Huntingtons disease?

Answer 24

30-50

Question 25

What is the inheritance pattern of huntingtons disease?

Answer 25

Autosomal dominant

Question 26

Where is the gene for huntingtons disease found?

Answer 26

Chromosome 4

Question 27

What is the mutation to the HTT gene that causes Huntington’s disease?

Answer 27

Expansion of CAG triplet repeat in HTT gene, causing it to become unstable and fragment, clumping together in nerve cells and damaging them

Question 28

How do we test the genome for huntingtons disease?

Answer 28

Using PCR to determine the length of the CAG repeat region which shows who will eventually develop the disease

Question 29

What is the phenotype of someone with 10-35 CAG repeats in the HTT gene

Answer 29

Normal

Question 30

What is the phenotype of someone with 27-35 CAG repeats in the HTT gene

Answer 30

Risk of descendants developing HD

Question 31

What is the phenotype of someone with 36-40 CAG repeats in the HTT gene

Answer 31

Risk of developing Huntington disease

Question 32

What is the phenotype of someone with 40+ CAG repeats in the HTT gene

Answer 32

Will develop Huntington’s disease

Question 33

What are the symptoms of Cystic Fibrosis?

Answer 33

- lung infections - pancreatic insufficiency - congenital absence of vas deferens in males - salty tasting skin

Question 34

What is the inheritance pattern of CF?

Answer 34

Autosomal recessive

Question 35

What is the mutated protein that causes CF

Answer 35

CFTR- cystic fibrosis transmembrane regulator (chloride ion channel)

Question 36

What does reduced function of the CTFR cause?

Answer 36

Thickening of cell secretions

Question 37

What is the most common mutation in the CTFR gene that causes CF?

Answer 37

3bp deletion, deltaF508, causes the protein to be abnormally processed and degraded

Question 38

What proportion of Northern Europeans carry the deltaF508 mutation?

Answer 38

1/25

Question 39

What is a potential reason that the harmful delay F508 mutation is still common in our populations?

Answer 39

Could provide a benefit to heterozygous individuals

Question 40

What are polygenic disorders?

Answer 40

Disorders involving several genes acting together or environmental factors interacting with genes

Question 41

What are some examples of polygenic disorders?

Answer 41

- obesity - diabetes - rheumatoid arthritis - gout - bipolar disorder