API

Relationship: 723

Title

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Altered, Chromosome number leads to Increase, Aneuploid offspring

Upstream event

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Altered, Chromosome number

Downstream event

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Increase, Aneuploid offspring

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Directness Weight of Evidence Quantitative Understanding
Chemical binding to tubulin in oocytes leading to aneuploid offspring directly leads to Strong

Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens Strong NCBI
mouse Mus musculus Strong NCBI

Sex Applicability

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Sex Evidence
Female Strong

Life Stage Applicability

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How Does This Key Event Relationship Work

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Development of a conceptus from a gamete containing an abnormal number of chromosomes results in an aneuploid offspring. Whether the aneuploid conceptus results in a viable offspring is dependent on the chromosome involved in the aneuploidy. Viable aneuploidies in humans include chromosomes 13, 18 and 21, and the sex chromosomes.

Weight of Evidence

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Strong.

Biological Plausibility

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It is well established that in the majority of cases of human offspring with an aneuploid condition, the extra chromosome is inherited from one of the parents. In humans, it is known that aneuploidy occurs more frequently in female germ cells. It has been known for a long time that there is a strong association between increasing maternal age and increasing risk of aneuploid offspring.

Empirical Support for Linkage

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Include consideration of temporal concordance here

Aneuploidy arising during meiosis in germ cells represents the most common chromosomal abnormality at birth and is the leading cause of pregnancy loss in humans. The presence of aneuploid eggs in humans ranges (depending on age), but is approximately 20%. In parallel, approximately 10–30% of human zygotes are aneuploid. 50% of human pregnancies are spontaneously aborted; of these, 50% are due to aneuploidly. Finally, approximately 0.3% of human newborns are aneuploid. These data are summarized in Hassold et al. (2007) and Nagaoka et al. (2012). It is widely accepted that human oocytes are particularly susceptible to induction of aneuploidy [Hassold et al., 2007; Hunt and Hassold, 2002; Nagaoka et al., 2012]. Trisomy 21 or Down syndrome, with an occurrence of ~1/720 births, is the most common genetic abnormality in newborns [Hassold et al., 2007]. The etiology of human aneuploidy is still not well understood, although there is strong evidence supporting a preferential occurrence during female meiosis I and a positive correlation with maternal age [Hunt and Hassold, 2002; Nagaoka et al., 2012].

Uncertainties or Inconsistencies

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None.

Quantitative Understanding of the Linkage

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Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

There is a direct relationship between the proportion of aneuploid eggs and the proportion of aneuploid offspring. Survival of the offspring depends on the affected chromosome.

Evidence Supporting Taxonomic Applicability

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This is based on evidence in humans and mice, but is broadly applicable to all eukaryotic species.

References

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