Genetic diagnosis 1 (Lucy)

Question 1

What ar ethe 4 types of genetic diseases that can arise from point mutations?

Answer 1

• Cystic fibrosis
• Phenylketonuria
• Achrondoplasia
• Osteogenesis imperfecta

Question 2

What type of disease is cystic fibrosis?

Answer 2

Loss of function, recessive

Question 3

What type of disease is phenylketonuria?

Answer 3

Loss of function, recessive

Question 4

What type of disease is Achrondoplasia?

Answer 4

Gain of function, dominant

Question 5

What type of disease is osteogenesis imperfecta?

Answer 5

Loss of function, dominant negative

Question 6

What are the main clinical symptoms of CF?

Answer 6

• Chronic pulmonary disease
• Pancreatic exocrine insufficiency
• Hepatic disease (liver)
• Intestinal abnormalities
• Infertility (urogenital abnormalities in males)

Question 7

Why so much focus on CF?

Answer 7

Most common life threatening disease in the UK

1 in 23 carry mutated CFTR gene (>2 million ppl)

Affects over 8000 ppl in the UK

43% of ppl w CF have diabetes

Question 8

What is the most common mutation in CF?

Answer 8

ΔF508

Question 9

What is ΔF508?

Answer 9

3bp deletion –> maintains fram but removes phenylalanine

Question 10

How many reported mutations are there in the CFTR gene?

Answer 10

Over 1000

Question 11

What is the mutation in PKU?

Answer 11

Splice site IVS12+G>A

Or missense = F39L or I65T

Question 12

What is affected in PKU?

Answer 12

The PAH enzyme

Has 21 exons over 80kb

Recessive disease - 2 mutations needed for phenotype

Question 13

What is the mutation called in ACH?

Answer 13

1138G>A

Question 14

What gene is affected in achondroplasia (ACH)?

Answer 14

FGFR3 gene

Occurs at a CpG site (G to A mutation)

Question 15

What is the amino acid change in ACH?

Answer 15

Gly380Arg

Question 16

What sort of disease is Alpha-thalassamia

Answer 16

Loss of function –> recessive

Question 17

What does the muation in Osteogenesis imperfect affect?

Answer 17

Collagen production

It is a dominant negative effect

Question 18

What is the genes affected in Osteogenesis imperfecta?

Answer 18

COL1A1 & COL1A2

(These code for type 1 procollagen)

Question 19

What is type 1 procollagen?

Answer 19

Made up of 3 amino acid chains encoded by COL1A1 and COL1A2

Question 20

What does a null mutation in either COL1A1 or COL1A2 cause?

Answer 20

Mild osteogenesis imperfecta

Question 21

What does a missense mutation in either COL1A1 or COL1A2 cause?

Answer 21

Severe osteogenesis imperfecta

Question 22

What sort of disease is CMT1A (charcot marie tooth) and PMP22 (pulmonary disease)?

Answer 22

Duplication, gain of function, dominant

Question 23

What sort of disease is Haemophillia A?

Answer 23

Loss of function, X-linked recessive

Question 24

What type of disease is duchenne muscular dystrophy (DMD)?

Answer 24

loss of function, X-linked recessive

Question 25

What type of disease are VCFS and WBS?

Answer 25

deltions, loss of function