Screening for human epigenetic variation at CpG islands

Mutations that alter the base sequence of DNA underlie many human characteristics, including susceptibility to disease. An alternative, but poorly characterised, potential source of human variation is ?epigenetic? in nature and involves stable changes in the marks and signals that influence local gene activity. Epigenetic phenomena are increasingly invoked as critical factors that affect health. With the exception of cancer, however, the data supporting a role for epigenetics in disease is limited and inconclusive. We have chosen a specific epigenetic phenomenon, CpG island methylation, and will screen human DNA samples from a variety of tissues to look for differences that correlate with age, sex or disease state.

Mutations that alter the base sequence of DNA underlie many human characteristics, including susceptibility to disease. An alternative, but poorly characterised, potential source of human variation is ?epigenetic? in nature and involves stable changes in the marks and signals that influence local gene activity. DNA methylation is known to inhibit gene expression, especially when the promoter concerned lies within a CpG island. CpG islands are predominantly unmethylated, but recent data shows that thousands become methylated in normal tissues and there is some evidence for variation between individuals. The present proposal seeks to characterise the extent of inter-individual variation in methylation of the complete human complement of 25,000 CpG islands. We will look for correlations of CpG island methylation with age, sex, and disease status in an attempt to assess the potential impact of epigenetic variability on health.