Chromosomal Abnormalities Flashcards
What is metaphase?
- Chromosomes are condensed and can be karyotyped during metaphase
- Each chromosome comprises two chromatids at this point
- 4n prior to cell division
How is DNA compacted?
Chromatin
•Its not just about fitting a lot of DNA into the cell
•Proteins bound to the chromatin affect its regulation
•The 3D genome is important
What is G banded architecture?
Ideogram
•Chromosomes have some common structural features
•Giemsa staining leaves a recognizable pattern of bands
When is expression?
- Can be tissue specific
- Can be at a specific time in development
- Can be in response to an event
What is the purpose of mitosis?
- To create two identical daughter cells
- For growth and repair
- To replace exhausted cells
- 2n to 2n
How do you culture and harvest?
- 0.5ml blood in 5ml culture medium
- Add phytohemagglutinin (stimulates lymphocytes to divide)
- Culture 48-72 hours
- Add colecmins (arrests cells in metaphase)
- Culture breifly; add hypotonic KCl to swell cells; fix in 3:1 methanol: acetic acid; drop on to microscopic slide
- Brief digestion with trypsin stain with Giemsa
What is the purpose of meiosis?
- To achieve reduction from diploid (2n=46) to haploid (n=23)
- To ensure genetic variation in the gametes
- Enables random assortment of homologues and recombination
Why is there vulnerability of female meiosis?
- Paused in utero until puberty
- One primary oocyte yields only one ovum
- Finite number of primary oocytes
What is female non-disjunction?
•Most aneuploidy caused by non-disjunction arises in oogenesis
•Likely due to degradation of factors which hold homologous chromatids together
-Risk of maternal non-disjunction increases with age
-First trimester risk for trisomy 13,18 and 21
When does most trisomy 21 arise?
Maternal non-disjunction
What is Chromosomal aneuploidy?
Meiotic non-disjunction
•Trisomy for all chromosomes has been detected prenatally
•Not all trisomies are compatible with life
•Monosomy is poorly tolerated
Why is sex chromosome imbalance tolerated?
- X-inactivation of excess X chromosomes
* Low gene content of Y chromosome
What reciprocal chromosomal abnormalities have in common?
- Carriers (1 in 1000) are usually phenotypically normal
- Chromosomes have to contort into unusual figurations to achieve synapsis at mitosis and meiosis
- Present a reproductive risk: increased chance of unbalanced gametes
What are unbalanced chromosomal abnormalities?
- Severity of phenotype is dependent on gene content of affected segment
- Trisomy is usually more tolerated than monosomy
- May arise de novo or from a reciprocal parental abnormality
Describe Contiguous gene deletion syndromes:
The ‘phenotype first’ approach
- Clinical approach to grouping children with similar developmental delay and/or dysmorphism, then looking for common genetic abnormalities
- Yielded many ‘classical’ contiguous gene deletion syndromes
