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Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers.  Nondisjunction is common during anaphase I or anaphase II of meiosis.  Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold...
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Updated: May 23, 2025

Semiconductor Sequencing for Preimplantation Genetic Testing for Aneuploidy
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Sequence diversity lost in early pregnancy.

Gudny A Arnadottir1, Hakon Jonsson2, Tanja Schlaikjær Hartwig3

  • 1deCODE genetics/Amgen, Reykjavik, Iceland.

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|May 21, 2025
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Summary
This summary is machine-generated.

Genetic factors contribute to early pregnancy loss. This study found that pathogenic small sequence variants in the fetus cause approximately 1 in 136 pregnancy losses, highlighting lost genetic diversity.

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Area of Science:

  • Genetics
  • Reproductive Biology
  • Genomic Medicine

Background:

  • Meiotic errors cause chromosomal abnormalities and pregnancy loss.
  • Genetic causes of euploid (normal chromosome number) pregnancy loss are largely unknown.
  • Understanding genetic factors in early pregnancy loss is crucial.

Purpose of the Study:

  • To characterize sequence diversity in early pregnancy loss.
  • To investigate the genetic origins of chromosomal abnormalities and de novo mutations in pregnancy loss cases.
  • To determine the contribution of pathogenic small sequence variants to pregnancy loss.

Main Methods:

  • Whole-genome sequencing of 1,007 fetal samples and 934 parental samples from 467 trios.
  • Analysis of parental and meiotic origins of chromosomal abnormalities.
  • Assessment and dating of de novo mutations and small sequence variants.

Main Results:

  • Chromosomal abnormalities were detected in half of the studied pregnancy loss cases.
  • Approximately 6.6% of maternal de novo mutations occurred before sister chromatid formation.
  • Pregnancy loss cases showed three times more pathogenic small sequence variant genotypes than adult controls.
  • Around 1 in 136 pregnancies are lost due to pathogenic small sequence variants in the fetus.

Conclusions:

  • Pathogenic small sequence variants are a significant cause of early pregnancy loss.
  • This study reveals substantial genetic diversity lost during early pregnancy.
  • Further research into genetic etiologies of pregnancy loss is warranted.