Numerical Chromosomal Abnormalities Flashcards
What are the 3 main stages of cell cycle?
Interphase - cell growth and DNA replication
Mitosis - duplicated genetic information is separated
Cytokinesis - division into 2 cells
What are the stages within interphase? and what happens in each
G1 - growth - cellular content not genetic info is duplication
S - synthesis - duplication of dna
G2 - checks duplicated chromosomes and repairs
G0 before g1 - cell cycle arrest
How do the sister chromatids and homologues interact?
They don’t. Sister chromatids (one duplicated and one original) attached to eachother until separation in mitosis whereas homologous (original maternal and paternal) do not interact.
What is a bivalent and when does it happen?
Bivalent structure is when homologous chromosomes align (after duplication of chromatids) to exchange genetic material in genetic recombination.
What happens in genetic recomination? and when does it happen?
Chromosomes crossover forming chiasma and reciprocal breaking and re-joining of homologous chromosomes in meiosis forms one set of recombinant chromosomes and a set of non-recombinant chromosomes.
What is the result/leftover after genetic recombination?
New allele combinations. On maternal set of sister chromatids, one chromosome is a recombinant chromosome, one if original and same goes for paternal set of sister chromatids
What are the phases in meiosis?
Meiosis 1 and 2
What happens in meiosis 1?
Bivalent alignment !!!
Chiasma form for recombination.
Homologues are pulled apart
2 daughter cells with 23 chromosomes in each cell but as sister chromatids
What happens in meiosis 2?
Independent chromosomes align!!
Sister chromatids are pulled apart
Daughter cell has 23 chromsomes but now 1 chromatid in each cell
How is natural variation introduced?
Indpependent assortment of chromosomes
Recombination
= unique daughter cells
What is independent assortment?
23 pairs of chromosome in beginning (1 of each pair from a parent, only 1 of each of the 23 chromosomes goes onto gametes, this random selection of maternal and paternal homologs is independent assortment) - some chromosomes will be maternal and some paternal AFTER MEISOSIS 1 DIVISION
Compare the cell cycle in mitosis vs meisosis
Both replicate DNA during interphase
Separation of HOMOLOGS only happens in meiosis 1
Separation of chromatids happen in meiosis 2 and mitosis
What is segregation?
Process of chromatid separation (in mitosis and meiosis 2)
Give examples of error in segregation
NON DISJUNCTION - Both pairs of sister chromatids go to one pole so daughter cells have too many or too little chromosomes
What happens if non disjunction occurs in gametes?
Chromosome imbalance so foetus ends up with too many or too little chromosomes
What is aneuploidy?
Having extra chromosomes or missing chromsomes e.g. trisomy
How many sets of chromosomes in haploid, diploid, triploid and tetraploid cels?
Haploid - 1 sister chromatid (N)
Diploid - 2 chromosomes (2N)
Triploid - 3 chromosomes (3N)
Tetraploid - 4 chromosomes (4N)
What increases the chance of non disjunction caused aneuploidy?
Increased maternal age
What are the 3 types of chromosome structures depending on p and q arms viewed on karyotypes?
Metacentric
Submetacentric
Acrocentric
What determines whether a chromosome is metacentric, submetacentric or acrocentric
Where the centromere is
Metacentric - p and q arms are even length
Sub metacentric - p arms are shorter than q
Acrocentric - long q arms and small p arms (no unique DNA on p arms)
How are numerical chromosomal changed identified?
Karyotyping, FISH, QF-PCR, NGS
How are structural chromosomal changed identified?
Karyotyping
FISH
arrayCGH
What is haploid and where is it found?
One set of chromosomes - in gametes
What is diploid and where is it found?
Cell contains 2 sets of chromosomes - in somatic cells (body cells apart from sperm and egg)
What is polyploid?
Multiple of haploid number e.g. triploid(3N) or tetraploid (4N)
What is aneuploid different to polyploid?
Chromosome is not exact multiple of haploid number(N) due to extra or missing chromosome
e.g. 2N + 1 examples are trisomy, monosomy
What causes aneuploidy?
Meiotic non disjunction - error in segregation of either chromosomes are segregation of chromatids - visualise this
WHEN does monosomy occur?
Fertilisation - Empty gamete from non disjunction is fertilised with normal gamete (N) so only one set of chromosomes (N) in zygote = monosomy
WHEN does trisomy occur?
After fertilisation. One gamete has 2 chromosomes and fertilisation adds another - 3 pairs in zygote = trisomy
Do all cells from one non disjunction end up in either trisomy or monosomy?
No, during division, though 1/2 of the 4 gametes will have too many or too little chromosomes, some gametes end up having one set of chromosomes (N) and when joined by another gametes (N) becomes 2N and is normal
Does errors in chromosomes segregation or chromatid segregation have more impact on the 4 games formed?
Chromosome segregation since all gametes end up having either 1 extra or no chromosomes at all since 2 daughter cells after meiosis 1 already cannot become normal after meiosis 2 but in chromatid segregation, mistake isn’t made until meiosis 2
What is an autosome?
Chromosomes that are sex chromosomes
Give examples of autosomal aneuploidy conditions which chromosome is affected?
Trisomy 21 = Down’s syndrome
Trisomy 13 = Patau’s syndrome
Trisomy 18 = Edward’s syndrome
Give examples of sex chromosome aneuploidies conditions? + number of chromosomes in end
Turners in females (one X is missing) - only 45 chromosomes in total
Triple X syndrome in females - 47 chromosomes in total
Klinefelters in males - an extra X or an extra Y (XXY or XYY) - 47 chromosomes in total
Where does aneuploidy happen in mitotic non-disjunction?
Post zygotic - only affects a proportion of cells unlike in meiotic non disjunction where all cells have anueploidy
Define mosaicism
Presence of 2 or more genetically different cell lines derived from a single zygote e.g. a proportion of cells may be trisomic
What are the 2 causes of mosaicism?
- Cell starts of with normal amount of some changes into aneuploidy after mitotic non disjunction
- Cell starts of aneuploidic from meiotic non disjunction then mitotic non disjunction also happens returning a cell line back into normal cells
What causes mitotic non disjunction to reverse meiotic non disjunction? + an example of this
Cells recongise wrong number of chromosomes and randomly gets rid of one (random) to become disomic e.g. trisomy rescue. Some cells don’t recognise and continue as usual - mosaicism
What is the clinical relevance of mosaicism?
Cause of varying severity e.g in down’s syndrome varies, mosaicism = less severe
- but despite mosaicism being less severe, more difficult to asses not knowing which cells/tissues/organs are affected e.g. which cells are disomic vs trisomic
What causes full trisomy/monosomy?
Non disjunction (meiotic and mitotic)
