DNA Testing

Question 1

What kind of inherited genetic disorder can lead to neurological disorder with loss of movement control?

Answer 1

unstable repeat expansions

Question 2

T/F Expansions typically occur in a single chromosome in adjacent fashion

Answer 2

True

Question 3

T/F tetranuleotide repeat is the most common form of unstable repeat expansion

Answer 3

False, tri-nucleotide repeat is

Question 4

T/F The presence of these repeat genes indicates that the disease will definitely be present

Answer 4

False, you can have naturally occurring repeats

it’s only when repeats exceed the threshold that the disease will develop

Question 5

What is dynamic mutation?

Answer 5

Means that in repeat expansions, the number of repeat can increase or decrease. The number of repeats is also not identical in every cell

Question 6

T/F the inheritance pattern can be quite variable

Answer 6

True, there is a range of fully penetrance type, and a range for incomplete penetrance etc.

Question 7

How do repeats in non-coding region cause disorders?

Answer 7

non-coding repeats can cause loss of protein function, or create a novel property to mRNA

Fragile X syndrome is an example for both

Question 8

How do repeats in coding region cause disorders?

Answer 8

change in codon sequence can give new property to encoded protein, and the protein becomes toxic

Question 9

What’s the challenge in diagnosing neurodegenerative disorders caused by repeat expansions?

Answer 9

the clinical presentation is very variable. Different diseases often present with similar clinical signs

Question 10

T/F Friedriech ataxia generally has an earlier onset than other disorders

Answer 10

True, usually earlier than HD and SCA

Question 11

T/F Huntington’s disease is an autosomal dominant disorder

Answer 11

True

Question 12

What are the main features of HD

Answer 12

movement disorder
cognitive disorder
emotional disorder

Question 13

T/F HD is caused by repeats of CCG in chromosome 4

Answer 13

False, it’s caused by CAG in chromosome 4

Question 14

T/F If you have more than 40 repeats in the gene huntingtin, you will definitely develop HD

Answer 14

True, >40 = fully penetrant

Question 15

What happens if an individual has 27-35 repeats in huntingtin?

Answer 15

The patient will not develop HD, but there may be expansion in sperm/egg, and offsprings are at risk of developing HD

Question 16

T/F PCR is accurate in diagnosing HD

Answer 16

False, it’s not accurate because DNA slipping (the mechanism of repeat expansion) occurs when doing PCR

Question 17

What is the main test for diagnosing HD?

Answer 17

fluorescent nucleotide testing

Question 18

Is predictive tests usually done for HD?

Answer 18

No, because there is no cure even if the condition is diagnosed

Question 19

T/F Spinocerebellar ataxia conditions are all caused by unstable repeats

Answer 19

False, only 10 types are caused by unstable repeats

Question 20

T/F Friedreich ataxia is an autosomal recessive disorder

Answer 20

True

Question 21

What is the proposed pathogenesis in FA?

Answer 21

there are repeats in introns which cause some secondary structural changes in DNA, so protein transcription is inhibited

Question 22

What are the main features of FA?

Answer 22

progressive limb and gait ataxia
cardiomyopathy
diabetes

Question 23

T/F The test for FA is simpler than that of HD

Answer 23

True, because there is usually massive repeat expansion in FA, so a simple gel electrophoresis can detect the genetic disorder

Question 24

How is FA treated nowadays

Answer 24

We can improve the movement disorder by surgically removing the contracture, but there is no therapy for cardiomyopathy and diabetes