Maternal influences on the transmission of leukocyte gene expression profiles in population samples from Brisbane, Australia.

Abstract

Two gene expression profiling studies designed to identify maternal influences on development of the neonate immune system and to address the population structure of the leukocyte transcriptome were carried out in Brisbane, Australia. In the first study, a comparison of 19 leukocyte samples obtained from mothers in the last three weeks of pregnancy with 37 umbilical cord blood samples documented differential expression of 7,382 probes at a false discovery rate of 1%, representing approximately half of the expressed transcriptome. An even larger component of the variation involving 8,432 probes, notably enriched for Vitamin E and methotrexate-responsive genes, distinguished two sets of individuals, with perfect transmission of the two profile types between each of 16 mother-child pairs in the study. A minor profile of variation was found to distinguish the gene expression profiles of obese mothers and children of gestational diabetic mothers from those of children born to obese mothers. The second study was of adult leukocyte profiles from a cross-section of Red Cross blood donors sampled throughout Brisbane. The first two axes in this study are related to the third and fourth axes of variation in the first study and also reflect variation in the abundance of CD4 and CD8 transcripts. One of the profiles associated with the third axis is largely excluded from samples from the central portion of the city. Despite enrichment of insulin signaling and aspects of central metabolism among the differentially expressed genes, there was little correlation between leukocyte expression profiles and body mass index overall. Our data is consistent with the notion that maternal health and cytokine milieu directly impact gene expression in fetal tissues, but that there is likely to be a complex interplay between cultural, genetic, and other environmental factors in the programming of gene expression in leukocytes of newborn children.