Molecular Genetics

Question 0

Define genetic linkage

Answer 0

The tendency of genes that are located proximal to each other on a chromosome to be inherited together during meiosis. Therefore, genes that are very close are more likely to be inherited together = genetically linked.

Question 1

What is Hybridization in microarrays?

Answer 1

Sequence specific interaction between complementary strands of nucleic acids

Question 2

Linkage mapping?

Answer 2

Map based on the frequencies of recombination during crossover of homologous chromosomes. Can locate genes by testing genetic linkage between two already known markers.

Question 3

What is LOD score?

Answer 3

Compares likelihood of getting data as a result of loci that are linked to getting the same data purely by chance.

Question 4

Recombination frequency

Answer 4

The frequency at which a single chromosome crossover will happen between two genes during meiosis.

Question 5

Centimorgan?

Answer 5

Unit that describes the recombination frequency of 1%

Question 6

Reason for cytogenetic referral

Answer 6

Congenital abnormality 
Fam hx
Abnormal ultrasound
Known translocation carrier
Recurrent miscarriage 
Advanced maternal age
Intellectual disability

Question 7

Limitations of cytogenetics

Answer 7

Labour intensive
Only large abnormalities
Trained staff needed

Question 8

What phase are chromosomes in when karyotyped

Answer 8

Metaphase

Question 9

Three classes of chromosomes

Answer 9

Metacentric - centromere in middle
Submetacentric - centromere off centre
Acrocentric - centromere at end

Question 10

Euploid

Answer 10

Any exact multiple of chromosome

Question 11

Aneuploid

Answer 11

Extra copy of absence of a chromosome

Question 12

Non-disjunction

Answer 12

Failure of chromosome to separate normally during cell division. Results in aneuploidy. More often maternal. Spindle centromere attachment error. Increase with maternal age.

Question 13

Trisomy 21

Answer 13

Downs syndrome

Question 14

Trisomy 18

Answer 14

Edward’s syndrome

Question 15

Trisomy 13

Answer 15

Patau syndrome

Question 16

45, X

Answer 16

Turner syndrome

Question 17

47, XXY

Answer 17

Klinefelter syndrome

Question 18

3 aetiologies of Down’s syndrome

Answer 18

Extra chromosome 21
Robertsonian translocation
Mosaic trisomy

Question 19

Six main chromosomal structural abnormalities

Answer 19

Deletion
Ring chromosome
Duplication
Isochromsome
Inversion
Translocation

Question 20

Two types of chromosome deletion

Answer 20

Terminal

Interstitial

Question 21

Isochrome?

Answer 21

Loss of one arm with duplication of the other.

Question 22

Inversion. Define and types

Answer 22

Two breaks in chromosome and fragment rotates.
Pericentric - involves both arms
Paracentric - involves only one arm

Question 23

Types of translocation

Answer 23

Reciprocal - break in two unrelated chromosomes, exchange of broken segments.
Robertsonian - two acrocentric chromosomes joined.

Question 24

Aneuploidy arises from..

Answer 24

Non-disjunction

Anaphase lag

Question 25

Uses of aneuploidy FISH

Answer 25

Test chromosomes 13, 18, 21, X and Y
Does not require cell culture
TAT of 1 or 2 days

Question 26

Limitations of FISH

Answer 26

Expensive, only test certain chromosomes
Lead patients into false sense of security
Cannot eliminate maternal contamination
Need good cell quality

Question 27

Advantages of QF-PCR over FISH

Answer 27

Cheaper, quicker, fewer cells, eliminate maternal contamination.

Question 28

Common micro deletion diseases

Answer 28

Do George 22
Prader Willi 15
Angelman 15
Miller Dieker 17
Williams 7

Question 29

What probes does FISH use when look for acquired haematological conditions

Answer 29

Break apart probes

Question 30

Synchronized culture

Answer 30

Block frolic acid pathway with methotrexate. Cell stay at G1/S. release with Thymidine. Cells go to G2. Harvest and stain.