Discovering candidate imprinted genes and Imprinting Control Regions in the human genome

Abstract

ABSTRACTGenomic imprinting is a process thereby a subset of genes is expressed in a parent-of-origin specific manner. This evolutionary novelty is restricted to mammals and controlled by genomic DNA segments known as Imprinting Control Regions (ICRs). The known imprinted genes function in many important developmental and postnatal processes including organogenesis, neurogenesis, and fertility. Furthermore, defects in imprinted genes could cause severe diseases and abnormalities. Because of the importance of the ICRs to the regulation of parent-of-origin specific gene expression, I developed a genome-wide strategy for their localization. This strategy located clusters of the ZFBS-Morph overlaps along the entire human genome. Previously, I showed that in the mouse genome, clusters of 2 or more of these overlaps correctly located ∼ 90% of the fully characterized ICRs and germline Differentially Methylated Regions (gDMRs). The ZFBS-Morph overlaps are composite-DNA-elements comprised of the ZFP57 binding site (ZFBS) overlapping a subset of the MLL1 morphemes. My strategy consists of creating plots to display the density of ZFBS-Morph overlaps along genomic DNA. Peaks in these plots pinpointed several of the known ICRs/gDMRs within relatively long genomic DNA sections and even along entire chromosomal DNA. Therefore, peaks in the density-plots are likely to reflect the positions of known or candidate ICRs. I also found that by locating the genes in the vicinity of candidate ICRs, I could discover potential and novel human imprinting genes. Additionally, my exploratory assessments revealed a connection between several of the potential imprinted genes and human developmental anomalies including syndromes.