In some organisms, including mammals, there is an inverse relationship between the presence of 5-methylcytosine (m5C) in CpG sequences and gene activity. In addition, m5C may be involved in the recruitment of proteins that convert chromatin regions from transcriptionally active to inactive states. Overall, genomic DNA is relatively poor in CpG sequences due to the conversion of m5C to thymine; however, unmethylated CpG islands are often associated with active genes. Researchers have determined that patterns of DNA methylation in spermatozoa vary with age in rats and suggest that such age-related alterations in DNA methylation may be one mechanism underlying age-related abnormalities in mammals (Oakes et al., 2003. Proc. Natl. Acad. Sci. 100: 1775–1780). In light of the above information, provide an explanation that relates paternal age-related alterations in DNA methylation to birth abnormalities.
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