Sequence diversity lost in early pregnancy

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.