Grant: Operating Grant

The purpose of this research program is to understand how genes involved in the development of male and female germ cells are regulated. A better understanding of the normal development of sperm and eggs, in particular, could permit the development of specific means to interfere with the process, including contraception, and provide a better understanding of infertililty. The chemical modification of genes, by DNA methylation, provides a way in which genes can be turned on or off at specific times. Major differences in DNA methylation have been found between the testis and the ovary and provide a way of marking the mothers and fathers genes differently. Differential marking of genes in the sperm and egg is being used to explain why genes responsible for human disease, such as growth disorders in children and cancer, may exert different effects depending on whether they come from an individuals mother or father. The objective of our research is to determine the regulation and role of DNA methylation in programming gene expression in the germline and the resulting embryo. The causes of approximately 70 percent of birth defects are unknown. It is anticipated that our studies will help explain and prevent some of the as yet unknown causes of birth defects in children.