Changes in the allelic methylation patterns of c-H-ras-1, insulin and retinoblastoma genes in human development

The methylation status of the c-H-ras-1, insulin and retinoblastoma genes was determined in human sperm, hydatidiform mole, fetal tissues, adult lymphocytes and adult kidney. Individual alleles of c-H-ras-1 and insulin were distinguishable due to presence of endogenous variable number of tandem repeat (VNTR) polymorphisms. Both alleles of the latter two genes were extensively methylated in sperm compared to the other tissues. Several sites within these genes were less methylated in fetal tissues and the two alleles were differentially methylated in some cases. The retinoblastoma gene was highly methylated in all tissues examined, with the exception of a single site that was under-methylated in sperm only. The sperm-specific methylation patterns in all three genes could represent imprinting of the parental chromosomes. Since 5-methylcytosine is inherently mutagenic, it is possible that methylation imprinting could alter the susceptibilities of human genes to point mutations.