Runs of Homozygosity and Epigenetic Deregulation of Genomic Imprinting

Abstract

Runs of homozygosity (ROH) are uninterrupted contiguous regions within the genome exhibiting allelic homozygosity (alleles are inherited from the same parent). Genome-wide analyses consistently demonstrate that megabase-scale ROH are ubiquitous in humans, reflecting individual demographic history. The number and length of ROH correlate increasingly with the degree of consanguinity and can be associated with genetic diseases in both inbred and outbred individuals. Genomic imprinting and uniparental disomy (UPD) are two additional phenomena dependent on parental-origin-specific inheritance that should be noted. Here, we propose genomic imprinting is dysregulated by ROH (functional analogs of segmental UPD or those partially affecting chromosomes) spanning imprinted loci resulting in a phenotype of an imprinting disorder. Interestingly, it has recently been shown that ROH in genomic/chromosomal regions harboring 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