Unknown,Transcriptomics,Genomics,Proteomics

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Molecular markers of predictive value associated with low birth weight

ABSTRACT: Sub-optimal fetal development is associated with an increased risk of developing cardiovascular disease, type 2 diabetes (T2D) and adiposity later in life. However, definitions of intrauterine growth restriction (IUGR) and small for gestational age (SGA) are based on simple statistical approaches that may misclassify infants with a normal developmental profile and vice versa. We used an unbiased global profiling approach to identify gene expression patterns in umbilical cord tissue from 38 infants and identified a set of 466 genes which separated the subjects into 2 distinct groups – one biased towards lower birth weight and one biased towards normal birth weight. The data suggest that approximately 30% of children of normal size have a molecular profile more typical of impaired fetal development and who may be on a programmed trajectory. Differences in expression between the two groups encompassed 384 upregulated and 82 downregulated genes. Molecular profiling at birth may have utility in identifying markers that potentially reflect antenatal developmental and may be predictive of future phenotypic development after birth. Importantly, it may provide an alternative to the current classification of infants using birth weights. RNA from umbilical cord tissue from full term neonates was extracted and hybridized. Separation into 2 distinct groups, independent of birth weight, but based solely on gene expression levels was analysed by Genespring. After appropriate statistical analysis, one group was keenly associated with a higher birth weight (22 samples) while the other was associated with a lower birth-weight (18 samples). Technical replicates were included for all 40 samples.

ORGANISM(S): Homo sapiens

SUBMITTER: Emilia Tng

PROVIDER: E-GEOD-24818 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:BACKGROUND: Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA. METHODS: The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (BW, 1698-4151g) and gestational ages (GA, 35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity. RESULTS: We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome. CONCLUSIONS: We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk. 8 umbilical cords form low birth weight babies, 8 umbilical cords from high birth weight babies, 14 umbilical cords from normal birth weigth babies, 7 matching the gestational ages of the low birth weigth group (norm1) and 7 matching the getsational ages of the high birth weight group (norm2). Replicates for array, cRNA and slide spotting REPLICATES: biological replicate: LBW_1, LBW_2, LBW_3A, LBW_3B, LBW_3C, LBW_4, LBW_5, LBW_6, LBW_7, LBW_8A, LBW_8B biological replicate: HBW_1, HBW_2A, HBW_2B, HBW_2C, HBW3, HBW4, HBW5, HBW6, HBW7, HBW8 biological replicate: norm1_1, norm1_2, norm1_3, norm1_4, norm1_5, norm1_7A, norm1_7B, norm1_7C, norm1_7D biological replicate: norm2_1, norm2_2, norm2_3, norm2_4, norm2_5, norm2_6A, norm2_6B, norm2_7 technical replicate: HBW_2A, HBW_2B, HBW_2C technical replicate: LBW_3A, LBW_3B, LBW_3C technical replicate: LBW_8A, LBW_8B techical replicate: norm1_7A, norm1_7B, norm1_7C, norm1_7D technical repliacte: norm2_6A, norm2_6B

Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu. Umbilical cord blood was drawn into Tempus Blood RNA tubes (Applied Biosystems) from children born between January and May 2010 at the maternity unit of Jorvi hospital (Espoo, Finland; n=48), maternity units of Tartu and PM-CM-5lva (Estonia; n=25), or two maternity departments in Petrozavodsk (capital of the Republic of Karelia, Russian Federation; n=40) according to the manufacturerM-BM-4s protocol and then stored in M-bM-^HM-^R70 M-BM-0C until analyzed. All newborn infants were full-term (>36 gestational weeks) and born vaginally. 113 cord blood RNA samples were analyzed with Affymetrix U219 gene array. Gender, pregnancy week, month of birth and HLA risk class were included as confounding factors in the analysis model.

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Molecular markers of predictive value associated with low birth weight

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