Fergus - Lecture 2

Question 1

What are the different branches of medical genetics?

Answer 1

Clinical genetics

Molecular genetics

cytogenetics

Question 2

What are clinical genetics?

Answer 2

Diagnostics of genetic disorders and genetic counseling for individuals or families with or at risk of conditions with a genetic basis

Question 3

What is cytogenetics?

Answer 3

How chromosomes relate to cell behaviour, particulary to their behaviour during mitosis and meiosis

Question 4

What is molecular genetics?

Answer 4

The manipulation of an organism’s genome

Question 5

What is medical genetics responsible for?
(4)

Answer 5

Diagnosis -> clinical or laboratory

Carrier detection -> pedigree analysis or lab analysis

Predictive testing -> pre-symptomatic diagnosis by DNA analysis

Genetic counselling

Question 6

What does ARMS stand for?

Answer 6

Amplification
Resistant
Mutation
System

Question 7

What is an ARMS PCR also known as?

Answer 7

Allele specific PCR

Question 8

How does an ARMS PCR work?
(5)

Answer 8

Primers are designed to amplify only the normal or only the mutated sequence

Based on the 3’ nucleotide of the primer matching exactly the target or mismatched

2 PCR reactions are performed

Normal primer, Mutation primer and common primer

The normal primer will only work on a normal sequence and a mutated primer will only work on a mutated sequence

Question 9

How many primers are needed for an ARMS PCR?

Answer 9

Three
Common, normal, mutated

Question 10

What is real time PCR?
(4)

Answer 10

PCR where we can detect products as they are being generate using fluorescent labelling

Dependent on fluorescent detection of PCR products during cycle

Two types: specific or non-specific

Non specific: DNA is split into single strands, fluorescent dyes are attached - the intensity of the fluorescence is measured

Specific: olgionucleotide probes labelled with fluorescent reporters, which permits detection only after hybridization of the probe with its complementary sequence

Question 11

What does SSCP stand for?

Answer 11

Single strand conformation polymorphism

Question 12

What is the basis of SSCP

Answer 12

Single-stranded DNA has a defined conformation

If mutated the single-stranded DNA will migrate differently during

Therefore mutant DNA samples display different band patterns.

Question 13

Write a note on fragile X chromosome
(5)

Answer 13

Most common form of male intellectual disability

Mutation in FMR1 gene

RNA binding protein associated with polyribosomes

Fragile site at Xq27

Incidence of 1/2000 males

Question 14

What causes fragile X?
(3)

Answer 14

Part of the long arm of chromosome X is damaged ‘fragile’ in affected males

Its caused by a mutation in the FMR1 gene located at Xq27

It affects an RNA binding protein associated with polyribosomes

Question 15

Can fragile X affect females?

Answer 15

It can cause a slight drop in IQ in females

Question 16

What type of mutation causes fragile X?
(3)

Answer 16

A trinucleotide repeat (CGG)

On the 5’ untranslated region of the FMR1 gene

Between 50 and 200 repeats

Question 17

What happens if you have 170 CGG repeats or over 200 CGG repeats?
(2)

Answer 17

Fragile X

Methylation of the promoter resulting in failure of the FMR1 gene

Question 18

The presence of what can help stabilise the FMR1 gene?

Answer 18

The presence of As in the sequence

Question 19

What happens if you have 34 repeats in huntingtons?

Answer 19

You are normal
>35

Question 20

What happens if you have 36 repeats in huntingtons?

Answer 20

You have huntingtons

Question 21

What happens if you have 39 repeats in huntingtons?

Answer 21

You will die

Question 22

Write a note on polyposis colon cancer
(5)

Answer 22

Dominant
1 in 10,000
mutation in APC gene
Mutation results in truncated protein
Detected using PTT

Question 23

What is PTT?

Answer 23

Protein truncating test