8. Aneuploidy and non-disjunction Flashcards

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1
Q

What causes random segregation of homologous chromosomes in meiosis?

A

Homologous chromosomes can randomly segregate if:
1) If chromosomes didn’t recombine - no chiasmata
2) If chiasmata are lost after recombination before segregation

In random segregation: 50% chance that segregate normally, 50% chance of mis-segregation

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2
Q

What causes random segregation of sister chromatids in meiosis?

A

Sister chromatids segregate randomly if:
all cohesin is degraded prematurely - no cohesin left at centromeres after meiosis I

In random segregation: 50% chance will segregate normally, 50% chance will mis-segregate

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3
Q

Define aneuploidy

A

Aneuploidy: abnormality in number of chromosomes due to loss/duplication

In gametes n -> 2n/0 is aneuploidy

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4
Q

What are the different types of aneuploidies in humans?

A

Normal chromosome number 2n, so common aneuploidies:
- n - monosomy (-n chromosome loss)
- 3n - trisomy (+n chromosome gain)

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5
Q

What are the most common aneuploidy syndromes in humans?

A

Most common aneuploidy syndromes:

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6
Q

Why is aneuploidy is badly tolerated?

A

Aneuploidy is badly tolerated due to gene dosage:
- some genes sensitive to quantity - aneuploidies of big chromosomes lethal (spontaneous abortion) - higher chance to get sensitive genes on large chromosome where many genes are held

  • majority genes not sensitive to dosage - aneuploidies in small chromosomes more viable - 21st/Y chromosomes small -> aneuploidy can be tolerated but with abnormal development
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7
Q

Is the natural rate of aneuploidy in gametes higher in men or women?

A

In women eggs rate of aneuploidy is higher than men’s sperm

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8
Q

Is natural rate of aneuploidy in gametes high in humans compared to other organisms?

A

Yes, in humans relatively very high rate of aneuploidy

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9
Q

What is an important factor affecting aneuploidy in women’s eggs?

A

Maternal age - biggest aneuploidy factor

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10
Q

Why is maternal age a factor in aneuploidy?

A

Due to female gametogenesis:
- all oocyte meiosis I occurs before birth - arrested in diplotene phase of prophase - further meiosis I + meiosis II after puberty - chromosomes don’t segregate until ovulation (that specific period)
- arrest = maternal age - long arrest - segregation only after arrest => cause not known yet but Cohesin ‘fatigue’ hypothesis

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11
Q

Why is paternal age not a factor of aneuploidy?

A

Because male gametogenesis is different:
- no meiotic arrest as in women - mitotic arrest
- mitosis + meiosis (chromosome segregation) constant throughout life until olf age - no arrest of specific sperm that would influence segregation quality

=> maternal arrest in oogenesis - the cause of aneuploidy in offspring

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12
Q

Explain what is the Cohesin ‘fatigue’ hypothesis

A

Cohesin ‘fatigue’ hypothesis - hypothesis to explain why maternal age has an inlfuence on chromosome missegregation - why long oocyte arrest leads to chromosome mis-segregation:

cohesin between sister chromatids established in S phase (established before birth) - majority of cohesin destroyed only left at centromeres - chromosome segregation only occurs at ovulation - arrest for x (maternal age) years => same cohesin molecule has ot remain stable for decades - cohesin might be unstable after many years of existing

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13
Q

How can the source (mother/father) of aneuploidy be studied in laboratory?

A

Edited chromosomes - molecular markers for maternal and paternal chromosomes - see which missing/extra chromosome copy in offspring responsible for aneuploidy

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14
Q

On a diagram how to figure out in which round of meiosis chromosome mis-segregation occurred?

A

Compare centromeres:
- if same -> homologous mis-segregated -> meiosis I failure
- if different -> sister chromatids mis-segregated -> meiosis II failure

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15
Q

In statistics, which meiosis is more common cause in which aneuploidies in humans?

A

Trisomy 16: maternal MI
Trisomy 18: maternal MII
Trisomy 21: maternal MI
Trisomy XXY: maternal MI / paternal MI

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16
Q

What biological processes can cause human aneuploidy?

A

Processes which can cause human aneuploidy:
- Maternal / paternal MI
- Maternal / paternal MII
- Post-zygotic mitosis in development

17
Q

What events in recombination can lead to aneuploidy?

A

Recombination events that can lead to aneuploidy:
- no recombination / chiasmata lost - no chiasmata - random homologous segregation => MI mis-segregation
- single recombination at telomeres - weak chiasmata - radom homologous segregation => MI mis-segregation
- recombination near centromere - chiasmata where kinetochores should form => MII mis-segregation