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Title: Developmental epigenetics in humans : can maternal nutritional status mediate DNA methylation in their offspring?
Author: Dominguez-Salas, Paula
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2013
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Animal studies show that periconceptional maternal supplementation with nutrients involved in the provision of methyl-groups can alter DNA methylation patterns in the offspring. This thesis examines possible associations between maternal nutrition and offspring DNA methylation patterns in humans in the context of seasonal influences. Two complementary studies were conducted in rural Gambia. The 'indicator' group enrolled 30 non-pregnant women and followed them monthly for one year, to measure dietary intakes and blood biomarker levels of choline, betaine, folate, methionine and vitamins B2, B6 and B12, as well as plasma homocysteine, S-adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH), cysteine and dimethylglycine (DMG). The 'main' group enrolled 136 mother-infant pairs, with infants conceived at the peak of the rainy (July to September) or dry (February to April) season. The same panel of blood biomarkers were measured on maternal samples collected early in pregnancy. In the infants, DNA methylation at seven metastable epialleles (MEs) was assessed. Significant seasonal variation was observed within the indicator group for dietary intakes of choline, betaine, folate and B2 and all metabolic biomarkers. A possible change in dependence between the betaine and folate pathways between seasons was identified. Within the main group, a seasonal variation was observed in both maternal biomarker levels and infant DNA methylation. The rainy season was associated with a higher maternal SAM:SAH ratio, higher concentrations of most methyl-donors (folate, betaine and methionine) and cofactors (B2 and B6) and higher infant DNA methylation. DNA methylation at the MEs studied was associated with B2, cysteine and the SAM:SAH and DMG:betaine ratios, but not with the other biomarkers. These data suggest that Gambian seasonality influences maternal methyl-group supply, which may be linked to DNA methylation patterns in offspring. Future work is required to confirm this observation, and understand precise mechanisms, so optimal nutrition at critical phases can be determined.
Supervisor: Hennig, B. J. ; Moore, S. Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral