Pluto Bioinformatics

GSE54016: The developmental dynamics and disease potential of random monoallelic gene expression

Bulk RNA sequencing

X-chromosome inactivation (XCI) in females and allelic exclusion of olfactory receptor or immunoglobulin loci, represent classic examples of random monoallelic expression (RME). RME of some single copy genes has also been reported, but the in vivo relevance of this remains unclear. Here we identify several hundred RME genes in clonal neural progenitor cell lines derived from embryonic stem cells. RME occurs during differentiation and once established, the monoallelic state can be highly stable. We show that monoallelic expression also occurs in vivo, in the absence of DNA sequence polymorphism, similarly to XCI. Several of the genes identified play important roles in development and have also been implicated in human autosomal dominant disorders. We propose that monoallelic expression of such genes contributes to the fine-tuning of the developmental regulatory pathways they control and in the context of a mutation, RME can predispose to loss of function in a proportion of cells and thus contribute to disease. SOURCE: Nicolas Servant (Nicolas.Servant@curie.fr) - Institut Curie