Replication Timing Predicts Underreplicated Domains in Polyploid Trophoblast Giant Cells

Abstract

s / Placenta 34 (2013) A1–A99 A8 migrants to high altitude. Our global hypothesis is that evolution has favored genes that may permit greater fetal growth even in the presence of hypoxia. Methods: Using microarrays, we compared placental RNA from 45 Native Americans versus Europeans. Our criteria for differentially expressed genes (DEGs) were a fold change > 1.25 with an adjusted p-value < 0.01. Results: There were only 10 DEGs in Andeans versus Europeans at 400 m. The most pronounced was localized to chromosome 19, is a member of the pregnancy specific glycoprotein family, and its expression is increased in Andeans. In contrast, there were 54 altitude-induced DEGs in the Europeans and 40 in the Andeans. These are ancestry dependent DEGs because there were only two shared between ancestry groups (Figure 1). There were 103 DEGs between the high and low altitude individuals irrespective of ancestry, including NOS3, a nitric oxide synthase, associated with the regulation of oxygen in hypoxic environments. Conclusion: These findings support the concept that the ancestry-environment interaction differs between Native American and European groups. Andeans at 3600 m showed enrichment of genes related to the HIF1 pathway, while there is over-representation of DEGs related to inflammation and coagulation in Europeans. Our current analyses target differences in placental morphometrics in relation to the DEGs reported here. Support: 1R211HD068954-01, NIHHD042737, NSFBCS0309142