Reading projects

"By reading only six hours a day", says Marianne Dashwood, outlining her plan of future application to her sister Elinor in Sense and Sensibility, "I shall gain in the course of a twelve-month a great deal of instruction which I now feel myself to want." She adds: "Our own library is too well known to me, to be resorted to for any thing beyond mere amusement. But there are many works well worth reading at the Park; and there are others of more modern production which I know I can borrow of Colonel Brandon" (301). We know, to some extent, what was in the Dashwoods' own library – volumes of Cowper, Scott and Thomson are mentioned. But what might Marianne have borrowed at Barton Park and Delaford? Which publications would Colonel Brandon have considered most appropriate for her project of self-improvement? Elinor considers Marianne's plan excessive, but what would have been a more realistic amount of time for her to spend reading each day, and where might she have done it

Additional file 2: Figure S2. of Methylome analysis for spina bifida shows SOX18 hypomethylation as a risk factor with evidence for a complex (epi)genetic interplay to affect neural tube development

Heatmap showing methylation of genes involved in the folate and one carbon metabolism in MMC patients. Methylation values of the genes are extracted from data obtained with the HM450k. Green and red represent 0 and 1 methylation, respectively. MMC: myelomeningocele. (TIF 12951 kb

Additional file 3: Figure S3. of Methylome analysis for spina bifida shows SOX18 hypomethylation as a risk factor with evidence for a complex (epi)genetic interplay to affect neural tube development

Mean methylation of SOX18 for MMC patients and controls according to MTHFR 677 C>T genotype by Sequenom EpiTYPER. Boxplot representing the methylation pattern of MMC patients and controls divided according to MTHFR 677 C>T genotype with box = 25th and 75th percentiles; bars = min and max values. The mean methylation level of each group is shown above the plot. (TIFF 337 kb

DNA methylation analysis of Homeobox genes implicates <i>HOXB7</i> hypomethylation as risk factor for neural tube defects

<div><p>Neural tube defects (NTDs) are common birth defects of complex etiology. Though family- and population-based studies have confirmed a genetic component, the responsible genes for NTDs are still largely unknown. Based on the hypothesis that folic acid prevents NTDs by stimulating methylation reactions, epigenetic factors, such as DNA methylation, are predicted to be involved in NTDs. Homeobox (<i>HOX</i>) genes play a role in spinal cord development and are tightly regulated in a spatiotemporal and collinear manner, partly by epigenetic modifications. We have quantified DNA methylation for the different <i>HOX</i> genes by subtracting values from a genome-wide methylation analysis using leukocyte DNA from 10 myelomeningocele (MMC) patients and 6 healthy controls. From the 1575 CpGs profiled for the 4 <i>HOX</i> clusters, 26 CpGs were differentially methylated (<i>P</i>-value < 0.05; β-difference > 0.05) between MMC patients and controls. Seventy-seven percent of these CpGs were located in the <i>HOXA</i> and <i>HOXB</i> clusters, with the most profound difference for 3 CpGs within the <i>HOXB7</i> gene body. A validation case-control study including 83 MMC patients and 30 unrelated healthy controls confirmed a significant association between MMC and <i>HOXB7</i> hypomethylation (-14.4%; 95% CI: 11.9–16.9%; <i>P</i>-value < 0.0001) independent of the <i>MTHFR 667C</i>><i>T</i> genotype. Significant <i>HOXB7</i> hypomethylation was also present in 12 unaffected siblings, each related to a MMC patient, suggestive of an epigenetic change induced by the mother. The inclusion of a neural tube formation model using zebrafish showed that Hoxb7a overexpression but not depletion resulted in deformed body axes with dysmorphic neural tube formation. Our results implicate <i>HOXB7</i> hypomethylation as risk factor for NTDs and highlight the importance for future genome-wide DNA methylation analyses without preselecting candidate pathways.</p></div