Numerical chromosomal abnormalities Flashcards
Describe the process of mitosis
- Cell division where somatic cells produced
- Interphase - Normal cell growth and duplication. This is where chromosomes duplicate themselves to produce 2 identical copies of each chromosome and this is also when protein synthesis occurs (specifically in G1)
- Mitosis - Duplicated organelles separate, occurs in all body cells bar sperm and egg
- At beginning of mitosis, chromosomes condense and become visible. Chromosomes consist of identical parts called sister chromatids, joined at the centromere
- Cell spindle fibres form, move to opposite poels of cell, forming web-like structure (prophase)
- This web-like structure pulls chromosomes so they line up in the centre of the cell spindle (metaphase)
- Sister chromatids pulled apart to opposite ends of cell (anaphase)
- Nuclear membrane forms around each set of chromosomes, and chromosomes uncoil (telophase)
- Cytokinesis - Cell divided into 2, cytoplasm divdies to produce 2 genetically identical daughter cells
Describe the process of meiosis
- Cell divsion where gametes are produced
- 2 step process split into meiosis 1 and meiosis 2
- Formation of n= 23 instead of 46 occurs during meiosis 1
- Chromosomes replicate in interphase (identical at this point to mitosis), align across spindle and undergo recombination where they exchange genetic material/genes (this is prophase I)
- Independent assortment of chromosomes occurs during metaphase I, this is when alleles of 2 or more different genes get sorted into gametes independently of one another. In other words, separate genes assort independently. In metaphase, the homologous chromosmes align together and physically exchange genetic material
- Following recombination, pairs of chromosomes pulled to ends of cells by spindle fibres, daughter cells formed
- In meiosis 2, sister chromatids separated, forming 4 haploid daughter cells - This differs from mitosis, as the chromatids are being pulled apart in meiosis 2, not meiosis 1, where they stay together, allowing for recombination and independent assortment.
Describe recombination/crossing over
Reciprocal breaking and re-joining of the homologous chromosomes in meiosis, results in exchange of chromosome segments and new allele combinations
Rather than rejoing to self, rejoins to partner, and forms structure called chiasma
THIS HAPPENS IN PROPHASE I
Describe what happens during metaphase I of meiosis
- Chromosomes are bivalent
- Chromosomes line up in middle of spindle
- Genes randomly assorted into chromosomes, resulting in genetic variation
What is the name of the complex between the homologous pairs of chromosomes?
Synaptonemal complex - Forms during prophase 1, mediates synapsis and recombination during meiosis
What is the chiasmata?
The chiasmata is the point of contact b/w the 2 non-sister chromatids of paired homolgous chromosomes
The X shape formed by crossover between 2 non-sister chromatids of 2 homologous chromosomes during prophase I of meiosis
When does separation of the sister chromatids occur in meiosis
Meiosis 2 (specifcally anaphase II)
When does separation of the homologous chromosomes occur in meiosis?
Meiosis 1 (anaphase I)
What is segregation?
Process of separating chromatids
Describe the normal human karyotype
- 22 pairs of autosomes
- 1 pair of sex chromosomes (XX or XY)
- Metacentric:
- P and q arms even length
- 1-3 and 16-18
- Submetacentric:
- P arm shorter than q
- 4-12, 19-20, X
- Acrocentric:
- Long q, small P
- P contains no unique DNA
- 13-15, 21-22, Y
Define haploid
1 set of chromosomes (n=23)
Define diploid
Cell contains 2 sets of chromosomes (2n = 46, normal in human)
Define polyploid
Multiple of the haploid number (e.g 4n = 92)
Define aneuploid
Chromosome number which is not exact multiple of haploid number - Due to extra or missing chromosomes e.g. 2n+1 = 47 (trisomy or monosomy)
What is meiotic non-disjunction?
During meiosis, the chromosomes/chromatids incorrectly separate, meaning the daughter cells will have either too many or too few chromosomes.
In meiosis, this means the resulting gametes are chromosomally unbalanced.
Explain the role of meiotic non-disjuntion in causing an abnormal number of chromosomes to arise
Meiotic non-disjunction is when the chromosomes inappropriately separate during meiosis I OR in meiosis II when the chromatids incorrectly separate. This means there’s unbalanced number of chromosomes within the resulting daughter cells (trisomy or monosomy etc)
Define mosaicism
The presence of two or more genetically different cell lines derived from a single zygote.
An error in mitosis means a cell doesn’t divide evenly into 2 cells, so end up trisomic or monosomic.
How does mosaicism occur as a result of mitotic non-disjunction?
Non-disjunction in mitosis is also called post-zygotic non-disjunction.
If chromosomes incorrectly separate during mitosis, the daughter cells have varying amounts of chromosomes, resulting in trisomy or monosomy.
Individual has mixture of cell types with respect to the chromosome complement.
Describe G banding
G = Giemsa
This is metaphase chromosome staining
Giemsa highlights heterchromatic regions which are less likely to contain genes. Banding can be used to differentiate b/w chromosomes and to compare them. It’s generally done at metaphase when the chromosomes are highly condensed.
Looks for aneuploidies, translocations and large deletions
Take several days at least
Bands because:
- 2 types of chromatin - Euchromatin and heterochromatin
- Euchromatin - GC rich, loosely packed, activate genes
- Heterochromatin - AT-rich, tightly packed, genes inactive
- Stain differently
What is FISH?
- Fluorescent in situ hybridisation
- Hydbridisation - Single stranded nucleic acid strand binds to a new single stranded nucleic acid strand (DNA/DNA or DNA/RNA)
- Uses metaphase chromosomes
- Looks for aneuploidies, translocations and large deletions
- Take several days at least
- Cultured cells, metapase spread:
- Fluorescent probe
- Denature probe and target DNA
- Mix probe and target DNA
- Probe binds to target
- Probes:
- Single stranded DNA or RNA molecule
- Typically 20-1000 bases in length
- Labelled with fluorescent or luminescent molecule (less commonly a radioactive isotope)
Describe QF-PCR
- Quantitative fluorescence polymerase chain reaction
- Uses microsatellites
- Trisomies 13 (Patau syndrome), 18 (Edwards syndrome) and 21 (Down’s syndrome)
- This method of analysis looks for how many copies of a chromosome patients have
