Chromosomal abnormalities Flashcards
Homologous chromosomes
What can be different between homologous chromosomes?
Chromosomes that have the same sequence of genes, that have the same structure, and that pair during meiosis
While they contain the same genes on them, the allelic forms may vary
Cell cycle phases
Interphase (G1, S, G2), mitosis, cytokinesis
G1 phase
Cell growth
-cells increase in size and synthesise new proteins and organelles needed for DNA replication
S phase
Synthesis
-chromosomes are replicated to that each chromosome now consists of two sister, identical chromatids
G2 phase
Cell Growth
- synthesis of protein, especially microtubules
- cell also double-checks the duplicated chromosome for any errors, making any needed repairs
Karyotype
A display of the chromosome pairs of a cell arranged by size and shape.
Types of chromosomes
Metacentric
Submetacentric
Acrocentric
Metacentric chromosome
- centromere is in the middle
- p and q arms even length
- chromosomes 1-3, 16-18
Submetacentric chromosome
- centromere is displaced toward one end
- p arm shorter than q arm
- chromosomes 4-12, 19-20, X
Acrocentric chromosome
- centromere located very close to one end
- small p arm, long q arm
- p arms contains no unique DNA
- chromosomes 13-15, 21-22, Y
Chromosomal changes can either be…
Numerical
OR
Structural
Haploid
Diploid
a cell that has one set of chromosomes (n=23)
-gametes
a cell that contains two sets of chromosomes (2n=46)
-autosomes
Polyploidy (numerical abnormality)
Aneuploidy (numerical abnormality)
A chromosomal alteration in which the organism possesses more than two complete chromosome sets
-multiple of the haploid number (e.g. 4n=96)
A chromosome number that is not an exact multiple of the haploid set
-due to extra or missing chromosomes (e.g. 2n+1=47)
Effect of numerical abnormalities on zygote
- Trisomy
- Monosomy
- Mosaicism
Describe bivalents and recombination
- Homologous chromosomes align and form om a bivalent structure
- They are stuck together by a synaptonemal complex
- This enables to exchange of genetic material at the chiasma (crossing over/recombination)
- forms recombinant chromosomes (new allele combinations)
Meiosis Summary
Two Meiotic Divisions
Meiosis I:
- homologous chromosomes ALIGN as bivalents
- allows for chiasma formation
- pulls apart homologues from one another (anaphase I)
- daughter cells have 23 chromosmes
Meiosis II:
- align as independent chromosomes
- sister chromatides pulled apart (anaphase II)
- 4 haploid daughter cells produced genetically different to parent cells due to genetic variation via allelic recombination
How does mitosis differ from meiosis?
- only a single round of cell division
- NO ALIGNMENT from homologous chromosomes, they just line up at the equator and pulled apart at anaphase (disjunction)
- diploid daughter cells produced which are genetically identical to parent cells
How does aneuploidy occur?
Autosomal aneuploidies
Non-disjunction in meiosis (I and II) and mitosis
- Trisomy 14 (Patau’s)
- Trisomy 18 (Edward’s)
- Trisomy 21 (Downs)
Sex Chromosome aneuploidies examples
Turners (45,X)
Triple X syndrome (47, XXX)
Kinefelter’s (47, XXY)
47, XYY
Meiotic non-disjunction
Non-disjunction occurring where there is impaired separation of either the homologous chromosomes in meiosis I or the chromatids in meiosis II
What does non-disjunction in meiosis cause after fertilisation with a normal gamete?
Whenever non-disjunction occurs, there is a mixture of trisomy and monosomy zygotes.
What is mosaicism?
the presence of two or more genetically different cell lines derived from a single zygote (should be identical)
What causes mosaicism?
Mosaicism is caused by 2 mechanisms:
· Post-zygotic (mitotic) nondisjunction= all 2n to mixture of 2n and 2n+1
· Anaphase lag, i.e. trisomic rescue= all 2n+1 to mixture of 2n+1 and 2n
Post-zygotic (mitotic) non-disjunction
Failure of sister chromatids to separate during anaphase of mitosis
-leads to mosaicism
Anaphase lag
one homologous chromosome in meiosis or one chromatid in mitosis fails to be included in the reforming nucleus
Instead, the lagging chromosome forms a micronucleus and is lost from the cell, resulting in one normal daughter cell and one with monosomy.
Trisomy rescue
Anaphase lag can also cause a rescue of the daughter cell if the cell was originally trisomy.
Clinical relevance of mosaicism
Mosaic phenotype is thought to be less severe
Difficult to assess
How does Turner’s syndrome occur?
Non-disjunction of the X chromosomes in meiosis I or II
Therefore at fertilisation, when either of the nullisomic daughter cells fertilise with a normal gamete (+X), results in Turner’s syndrome (XO).
