Runs of Homozygosity and Epigenetic Deregulation of Genomic Imprinting

Abstract

Runs of homozygosity (ROH) are uninterrupted continuous regions within the genome exhibiting allelic homozygosity (identical alleles are inherited from each parent). Genome-wide analyses consistently evidence that megabase-scale ROH are ubiquitous in humans reflecting individual demographic history. The number and length of ROH increasingly correlate with degree of consanguinity and are likely to be associated with genetic diseases both in inbred and outbred individuals. It is noteworthy that there are two other phenomena dependent on parental-origin-specific inheritance. These are genomic imprinting and uniparental disomy. Here, we propose ROH (functional analogues of segmental uniparental disomy or a uniparental disomies partially affecting chromosomes) spanning imprinted loci to be able to deregulate genomic imprinting resulting in a phenotype of an imprinting disorder. Interestingly, it has been recently shown that ROH at genomic/chromosomal regions, harbouring imprinted disease genes, are likely to be associated with brain diseases phenotypically resembling imprinting disorders (Angelman, Beckwith–Wiedemann and Prader–Willi syndromes). Therefore, ROH spanning the imprinted genes seem to be a feasible focus of basic and diagnostic research in epigenomics. Understanding the interplay between ROH and genomic imprinting is likely to illuminate a new epigenetic disease mechanism.