Sequence variation and DNA methylation patterning

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DNA can be modified by the addition or removal of small chemical tags which can have profound repercussions on the organism; why is a skin cell a skin cell and not a brain cell? Why is a blood cell a blood cell and not a heart cell? The addition and removal of chemical tags to DNA is thought to be responsible for these different cell fates, which explains why cells with identical genomes can have completely different identities (eg heart cell vs a blood cell). The long term objectives of this research program are to understand how and why this particular chemical tag gets added to DNA. What factors contribute to the addition of these tags? At what point are they added or removed from DNA to influence cell fate decisions? Is there cellular architecture required for the maintenance of these chemical tags? Given that there are a number of factors that can influence the addition of these chemical tags to DNA, the current research program will investigate how one of these factors, flanking DNA regions, influence these chemical tags. Specifically, it will address the relationship between, normal non-pathogenic deletions in the genome to theses chemical tags. To do this, we will select sites of common DNA sequence variation that are near well known sites of DNA chemical tags (called methyl groups). We will study people with DNA alterations at each of these sites and people without DNA alterations at these sites, and assess the local methylation pattern of the DNA in these healthy individuals. We hypothesize that DNA sequence variation will influence the patterning of the chemical tags in these local regions. ********************