Genetics Clinical Diagnosis

Question 1

Lab tests used to diagnose genetic conditions can be ordered at

1. […] level (cytogenic tests)
2. […] level (molecular tests)
3. […] level (biochemical tests)

Answer 1

Lab tests used to diagnose genetic conditions can be ordered at

1. Chromosomal level (cytogenic tests)
2. RNA/DNA level (molecular tests)
3. Protein/Product level (biochemical tests)

Question 2

A karyotype is […]

Answer 2

A karyotype is the examination under the microscope of whole chromosomes for the presence of abnormalities
Looking for numerical or structural abnormality

Question 3

Advantage and disadvantage for FISH

[…]

Answer 3

Question 4

Advantage and disadvantage for Karyotyping

[…]

Answer 4

Question 5

Advantage and Disadvantage of RNA based tests (uncommon):

[…]

Answer 5

Unlike DNA, different RNA is expressed only in certain type of tissue}}

Question 6

Advantage and disadvantage of tests looking directly/indirectly at protein/gene product
[…]

Answer 6

Advantage and disadvantage of tests looking directly/indirectly at protein/gene product

**Advantage
- Cheap, fast, relevant

**Disadvantage
- Protein might be inaccesible
- might not be the real reason for symptom

Question 7

Advantage and limitation of chromosomal microarray analysis

[…]

Answer 7

Question 8

Chromosomal Microarray Analysis is a […]

It is used for

[…]

Answer 8

Chromosomal Microarray Analysis is a “gene chip” test where
** Many FISH probes are placed on a chip and the probes are designed so as to cover the whole genome*
** The probes are also smaller so they can detect smaller duplications/deletions in the chromosomes*

It is used for

Question 9

FISH (fluorescence in situ hybridization) is […]

Answer 9

FISH (fluorescence in situ hybridization) is a cytogenetic test used to detect and localize the presence or absence of specific DNA/mRNA sequences.

cytogenetic tests

Heat the DNA, put in your fluoroscent DNA probe and let it reanneal back with probe.

Question 10

Levels of clinical genetic diagnosis

1. […]
2. […]
3. […]
4. […]

Answer 10

Levels of clinical genetic diagnosis

1.* Symptomatic diagnosis*
2. Pre-symptomatic diagnosis
3.* Carrier diagnosis*
4. Pre-natal diagnosis

Question 11

Main ways of making a clinical genetic diagnosis

1. […]
2. […]

Answer 11

Main ways of making a clinical genetic diagnosis

1. Clinical skills (History and physical examination)
2. Investigations (lab tests and non-lab tests)

Question 12

Name some types of RNA based tests:

[…]

Answer 12

Name some types of RNA based tests:

***VUS is variant of unknown significance. when you dont know the clinical impact of a certain mutation (can be beneficial, harmful or neither)
*

Molecular tests

Question 13

Protein/Product Base Testing done by

either
[…]

Answer 13

Protein/Product Base Testing done by

either
1.* looking directly at protein/gene product*
- amount
- function
- structure
2. looking indirectly at the function of protein

Question 14

Silent vs nonsense vs missense mutation and clinical significance

[…]

Answer 14

Question 15

When to suspect genetic disorder

Answer 15

When to suspect genetic disorder

• recurrent miscarriages/still births/neonatal deaths/ childhood deaths
• familial occurence
• individual with 2 or more malformations
• individual with multi-systemic disease
• disorder that resembles one known to have a genetic component

Question 16

why we do whole exome sequencing instead of whole genome sequencing.

Answer 16

why we do whole exome sequencing instead of whole genome sequencing.

current technlogy more cost-effective to screen whole exomes than whole genomes
*
**about 85% of disease causing mutations come from whole exome.*****