Post-implantation analysis of genomic variations in the progeny from developing fetus to birth

TL;DR

This study examines de novo mutations in human offspring from the fetal stage to birth, finding significant differences in indels between multifetal reduction and newborn groups.

Contribution

The study provides new insights into the decrease of de novo indels during embryonic development and their impact on genetic selection.

Findings

Newborns had significantly fewer de novo indels compared to the multifetal reduction group.

De novo indels decreased significantly from embryonic tissues to birth, affecting all genomic regions.

Adjusting for parental age and BMI revealed significant differences in de novo mutations between groups.

Abstract

The analysis of genomic variations in offspring after implantation has been infrequently studied. In this study, we aim to investigate the extent of de novo mutations in humans from developing fetus to birth. Using high-depth whole-genome sequencing, 443 parent-offspring trios were studied to compare the results of de novo mutations (DNMs) between different groups. The focus was on fetuses and newborns, with DNA samples obtained from the families’ blood and the aspirated embryonic tissues subjected to deep sequencing. It was observed that the average number of total DNMs in the newborns group was 56.26 (54.17–58.35), which appeared to be lower than that the multifetal reduction group, which was 76.05 (69.70–82.40) (F = 2.42, P = 0.12). However, after adjusting for parental age and maternal pre-pregnancy body mass index (BMI), significant differences were found between the two groups. The analysis was further divided into single nucleotide variants (SNVs) and insertion/deletion of a small number of bases (indels), and it was discovered that the average number of de novo SNVs associated with the multifetal reduction group and the newborn group was 49.89 (45.59–54.20) and 51.09 (49.22–52.96), respectively. No significant differences were noted between the groups (F = 1.01, P = 0.32). However, a significant difference was observed for de novo indels, with a higher average number found in the multifetal reduction group compared to the newborn group (F = 194.17, P < 0.001). The average number of de novo indels among the multifetal reduction group and the newborn group was 26.26 (23.27–29.05) and 5.17 (4.82–5.52), respectively. To conclude, it has been observed that the quantity of de novo indels in the newborns experiences a significant decrease when compared to that in the aspirated embryonic tissues (7–9 weeks). This phenomenon is evident across all genomic regions, highlighting the adverse effects of de novo indels on the fetus and emphasizing the significance of embryonic implantation and intrauterine growth in human genetic selection mechanisms.

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