16, 17 Chromosomal Abnormalities And Diagnostic Testing In Genetics

Question 1

What is cytogenetics?

Answer 1

Study of genetic consultation of cells through visualisation and analysis of chromosomes

Question 2

Why carry out cytogenetic analysis?

Answer 2

Accurate diagnosis/prognosis
Assess reproductive risks
Prenatal diagnosis

Question 3

Describe chromosomal analysis and reporting

Answer 3

Karyotyping

• metaphase chromosomes stained, paired up, grouped
• abnormalities described with standard nomenclature

Report

• chromosome no.
• sex complement
• structural changes
• separated by commas

Question 4

What is aneuploidy?

Answer 4

Loss/gain of whole chromosomes in cells

Question 5

2 causes of aneuploidy?

Answer 5

1. Non-disjunction
   - failure of chromosomes/sister chromatids to separate properly during meiotic/mitotic divisions.
2. Anaphase lag
   - defect in spindle function or attachment to chromosome. Lagging chromosome may be lost in mitosis/meiosis

Question 6

What is mosaicism?

Answer 6

One zygote
Mitotic division - non-disjunction
One of these cells has a change in mutation leading to two cell populations in an individual

Degree of mosaicism depends on when error occurs:

1. First post-zygotic division - no mosaicism and looks like a meiotic event
2. Subsequent divisions - 3 cell lines, monosomy cell line usually lost

Question 7

What is trisomy?

Answer 7

Extra copy of chromosome e.g. Down syndrome

Question 8

What is monosomy?

Answer 8

Presence of only 1 chromosome from a pair

Question 9

What is polyploidy? How does it occur?

Answer 9

Gain of whole haploid set of chromosomes, usually due to fertilisation of egg by more than 1 sperm

Question 10

What are cytogenetic structural abnormalities?

Answer 10

1. Translocations
2. Inversions
3. Deletions
4. Duplications
5. Insertions
6. Marker chromosome
7. Isochromosome
8. Reciprocal translocation

Question 11

What is a reciprocal translocation?

Answer 11

Two break rearrangement, exchange of material between non-homologous chromosomes

1. Balanced - same amount of genetic material spread across chromosomes
2. Unbalanced - deletion/addition of genetic material (abnormal phenotype)

Question 12

What is a robertsonian translocation?

Answer 12

Rare form of chromosomal rearrangement that in humans occurs in five Acrocentric chromosome pairs (13, 14, 15, 21, 22). Other translocations occur but do not lead to a viable foetus.

Question 13

What is the result of a segregation at meiosis?

Answer 13

Alternate, adjacent 1, adjacent 2, 3:1 non-disjunction, 4:0 non-disjunction

Question 14

What is an alternate meiotic disjunction?

Answer 14

Homologous centromeres segregate together, produce normal or balanced chromosomes

Question 15

What is an adjacent 1 segregation?

Answer 15

Adjacent non-homologous centromeres segregate together, unbalanced

Question 16

What is an adjacent 2 segregation?

Answer 16

Adjacent homologous centromeres segregate together, unbalance, rare

Question 17

What is a 3:1 non disjunction?

Answer 17

3 centromeres to 1 cell, 1 centromere to the other

Question 18

What is uni parental disomy (UPD)? What are the 4 types?

Answer 18

Presence of homologous chromosomes from one parent only

1. Isodisomy - 2 identical chrom from one parent
2. Heterodisomy - 2 homologous chrom from one parent
3. Segmental UPD - only part of chrom involved
4. Acquired UPD - solid tumours and leukaemias

Question 19

Four common mechanism to generate a UPD

Answer 19

Each require two separate abnormal events

1. Trisomy rescue
2. Monosomy rescue
3. Gamete complementation
4. Mitotic error