18.01.15 Origin of anueploidy Flashcards
What is anueploidy?
Presence or absence of chromosome(s) on a diploid background -> unbalanced chromosome complement, monosomy, trisomy. Not triploidy (extra set of chromosomes)
What is synapsis?
Synapsis: Pairing of chromosome homologues during prophase I (zygotene) and the formation of the synaptonemal complex, which is a protein assembly that holds together homologous chromosomes during prophase of the first meiotic division
What is recombination/crossing over?
DNA exchange between non-sister chromatids generating genetic variation
What is the function of chiasmata?
Join bivalents together.
What is the function of cohensin?
Join bivalents together.
What is segregation?
How the chromosomes are distributed in the cell/which pole they go to.
What is non-disjunction?
How the chromosomes are distributed in the cell/which pole they go to.
What is pachytene?
Third stage of prophase of meiosis I during which recombination (crossover) occurs
What errors at meiosis I can lead to aneuploidy?
MI error during gametogenesis (Meiosis) – affects entire chromosomes
a) Recombination failure b) Premature homologue separation c) True non-disjunction d) Premature sister chromatid separation
What errors at meiosis II can lead to aneuploidy?
MII error during gametogenesis (Meiosis) – affects sister chromatids
a) non-disjunction b) premature sister chromatid separation
How does recombination failure lead to aneuploidy? Give an example.
Recombination failure / Achiasmatic non-disjunction.
Achiamastic: the failure to establish recombination points (chiasmata) between homolog pairs.
Failure to form chiasmata, or premature resolution of chiasmata can result in homologs segregating to the same pole at MI, leading to non-disjunction.
Examples:
paternal X-Y non-disjunction (50% of XXY cases).
maternal T21 (40% of cases)
maternal UPD 15 (20% of cases)
How does premature homologue separation lead to aneuploidy? -
Premature homologue separation
Loss of cohesion between homologous chromosomes.
Bivalents segregate in MI largely under the influence of the Spindle Assembly Checkpoint (SAC).
What is true non-disjunction?
Failure of chiasmata between homologous chromosomes to resolve at anaphase I, both homologues therefore segregate to the same pole. In males this would produce 2 nullisomic and 2 disomic sperm.
What is PCS?
Premature sister chromatid separation (PSCS)
Deterioration of sister chromatid cohesion.
MI: Cohesion along chromosome arms keeps bivalents intact. MII: Cohesion along centromeres holds sister chromatids together.
Advancing maternal age may cause decreased cohesion of sister chromatids ⇨Sister chromatids separate early and travel to separate poles during MI
For segregation of chromosomes 16, 18, 21 and the X chromosome both non-disjunctional (75%) and PSCS errors (25%) have been observed. The presence of a pericentromeric exchange might increase the likelihood of chromosome ‘entanglement’ or PSCS at MI. Subsequent segregation at MII would result in a disomic gamete having identical centromeres — so the case would be scored as originating at MII even though the precipitating event occurred at MI. Therefore, MII non-disjunction may actually originate from an event in MI.
What is anaphase lag?
A chromosome fails to attach to the spindle apparatus, or is slowly pulled to its pole, and therefore fails to be included in the reforming nuclear membrane. In the cytoplasm it will form its own micronucleus and eventually be lost.