Cytogenetics 1

Question 1

What is a chromosome?

Answer 1

a threadlike structure of nucleic acids and protein found in the nucleus of most living cells, carrying genetic information in the form of genes. Has shot arm (p), long arm (q) and centromere.

Question 2

What are some clinically relevant chromosome abnormalities?

Answer 2

Constitutional Karyotype
Somatic Karyotype
Broken down into: Numerical Abnormalities and
Structural Abnormalities

Question 3

Constitutional Karyotype vs Somatic Karyotype

Answer 3

Constitutional: -Balanced… unusually no phenotype effect, except with fertility.
-Unbalanced… phenotype effect
Somatic (oncology): -Balanced vs Unbalanced
- Will only see abnormal karyotype in the tumour! Not in the blood!
-Pronostic value = metastisize?
-Targeted value = treatment kill only cell of this abnormality!

Question 4

Structural Chromosomal Abnormalities?

Answer 4

Caused by chromosome breakage and illegitimate reunion.
Types: Balanced..
- Robertsonian Translocation, Reciprocal Translocation, Inversions, and insertions
Unbalanced..
- deletion, duplication, derivative chromosome, ring chromosome, marker chromosome

Question 5

Robertsonian Translocation

Answer 5

Afrocentric chromosomes! Chromosomes are attached together! Can either be Homologous or heterologous (if it is two chromosome 21’s that join together, this is homologous). Thus only have 45 chromosomes, although no abnormal phenotype (balanced)!

Question 6

Reciprocal Translocation

Answer 6

Position change of two pieces of chromosomes.. ex. piece of 20 switches with piece from chromosome 4

Question 7

Inversions

Answer 7

Arise from two chromosomal breaks. Paracentric inversion does NOT include the centromere(two breaks in one arm). Pericentric inversion DOES include the centromere.
Results in chromosomal unbalanced gametes following crossing over. Detect with G-banding or FISH

Question 8

Insertions

Answer 8

Chromosomal material from one chromosome is inserted into an illegitimate location. Disrupts surrounding genes.
-Detect with G-banding or FISH

Question 9

Deletions

Answer 9

Loss of a segment of DNA from a chromosome. Can be interstitial or terminal. Caused by two breaks, followed by faulty repair.
-Detect with G-banding, FISH, array CGH

Question 10

Duplications

Answer 10

Presence of two adjacent copies of a chromosomal segment, can be direct or inverted. Arises by unequal crossing over in a previous meiosis, or translocation or inversion in parent.
-Detect with G-banding, FISH, Array CGH

Question 11

Consequences of Balanced Structural Rearrangements

Answer 11

• LOW phenotypic risks

- mainly infertility and reproductive risks!

Question 12

Genome Wide screen

Answer 12

Karyotype is genome wide screen analyses. Don’t look only at what you’re looking for. It is very subjective! Different resolutions bring different images!

Question 13

Karyogram vs Karyotype

Answer 13

Karyogram: Images
Karyotype: Results of the analysis. (ex. 46,XY)

Question 14

Understand the analysis and interpretation of cytogenetic abnormalities for selected human genetic disease

Answer 14

understand how microarrays are being used now in clinical genetics

Question 15

Array Comparative Genomic Hybridization (Array CGH/ microarray)

Answer 15

• DNA based technique, use peripheral blood samples.
• Array CGH allows for the detection of chromosome imbalances (missing or extra genetic info, that are small and cannot be detected by routine karyotype

Question 16

How are Microarrays being used now in clinical genetics?

Answer 16

Pre and post natally!

When come with clinical indications… can use CNV (copy number variations which show losses and gains)