Discovering candidate imprinted genes and imprinting control regions in the human genome

Background: Genomic 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) and germline Differentially Methylated Regions (gDMRs). Previously, I showed that in the mouse genome, the fully characterized ICRs/gDMRs often includes clusters of 2 or more of a set of composite-DNA-elements known as ZFBS-morph overlaps.

Results: Because of the importance of the ICRs to regulating parent-of-origin specific gene expression, I developed a genome-wide strategy for predicting their positions in the human genome. My strategy consists of creating plots to display the density of ZFBS-morph overlaps along the entire chromosomal DNA sequences. In initial evaluations, I found that peaks in these plots pinpointed several of the known ICRs/gDMRs along the DNA in chromosomal bands. I deduced that in density-plots, robust peaks corresponded to actual or candidate ICRs in the DNA. By locating the genes in the vicinity of candidate ICRs, I could discover potential imprinting genes. Additionally, my assessments revealed a connection between several of the potential imprinted genes and human developmental anomalies. Examples include Leber congenital amaurosis 11, Coffin-Siris syndrome, progressive myoclonic epilepsy-10, microcephalic osteodysplastic primordial dwarfism type II, and microphthalmia, cleft lip and palate, and agenesis of the corpus callosum.

Conclusion: With plots displaying the density of ZFBS-morph overlaps, researchers could locate candidate ICRs and imprinted genes. Since the datafiles are available for download and display at the UCSC genome browser, it is possible to examine the plots in the context of Single nucleotide polymorphisms (SNPs) to design experiments to discover novel ICRs and imprinted genes in the human genome.