Chromosome Abnormalities Flashcards
(22 cards)
Light bands vs dark bands of chromosomes (when do they replicate, is chromatin condensed, what are they rich in)
- Light replicate early in S phase, dark late
- Light have less condensed chromatin, dark have condensed
- Light are gene and GC rich, dark AT rich)
What is the DNA above and below the centromere on a chromosome called?
- Above = short arm (p)
- Below = long arm (q)
3 methods of examining chromosomes
- Karyotype
- Fluorescent in situ hybridisation (FISH)
- Array CGH
How does fluorescent in situ hybridisation work and what does it show?
- Fluorescent probes hybridise to specific areas of interest
- Shows if a patient has extra or missing bits
How does array CGH work?
- You have green test DNA and red reference DNA
- A DNA microarray is prepared with probes representing regions of interest
- The two DNAs are allowed to compete for the probes
- If the test is the same as reference, it will appear yellow, if extra in test then it will be green and if missing in test then it will be red
2 classifications of chromosome abnormality
- Abnormalities of number
- Abnormalities of structure
What is the general format of writing a karyotype?
Total number of chromosomes, sex chromosomes, abnormalities (eg. male with trisomy 21 = 47,XY,+21)
Types of abnormality of chromosome number
- Trisomy (3 chromosomes of one number)
- Monosomy (1 chromosome of one number)
- Triploidy (3 sets of chromosomes (ie. 69)
- Tetraploidy (4 sets of chromosomes (ie. 92)
Most frequent abnormalities of chromosome number in liveborn
- Autosomes
> Down syndrome (47,X_,+21)
> Edwards syndrome (47,X_,+18)
> Patau syndrome (47,X_,+13) - Sex chromosomes
> Turner syndrome (45,X)
> Klinefelter syndrome (47,XXY) - All chromosomes
> Triploidy
Proportions of different genetic causes of Down syndrome
- Non-disjunction in meiosis II leading to 2 copies in one gamete = 95%
- Robertsonian translocation = 4%
- Mosaicism due to non-disjunction after fertilisation = 1%
Symptoms of Edwards syndrome
Multiple malformations especially of the heart and kidneys
Symptoms of Klinefelter syndrome
- Infertility
- Poorly developed secondary sexual characteristics
- Tall
Symptoms of Turner syndrome
- Short stature
- Primary gonadal failure
Abnormalities of chromosome structure
- Translocations (Robertsonian and reciprocal)
- Deletion
- Duplication
- Inversion
- Ring chromosome
- Marker chromosome
- Complex rearrangements
How does a Robertsonian translocation work?
- 2 acrocentric chromosomes break at or close to the centromere
- Long arms fuse
- Short arms are lost
2 types of Robertsonian translocation
- Balanced
- Unbalanced
What is a balanced Robertsonian translocation?
All chromosome material is present, just in a different location (eg. person has 1 chromosome 14, 1 chromosome 21 and 1 chromosome containing both)
What is an unbalanced Robertsonian translocation?
Offspring inherit both normal chromosomes of one pair, but get a third copy of that pair attached to a different pair
What is an acrocentric chromosome and which are acrocentric?
- Chromosomes where the centromere is not central and instead very close to one end
- 13, 14, 15, 21, 22
How does a reciprocal translocation work?
- 2 non-homologous chromosomes break
- The fragments are exchanged
What can reciprocal translocations cause in offspring and how?
- Partial trisomy/monosomy
- They receive 1 normal chromosome from one parent and 1 chromosome with a bit missing/extra from the other
How do large chromosome deletions/duplications occur?
Unequal crossing over in meiosis following a mispairing at sites of repeated sequences
