Random monoallelic expression in mouse olfactory sensory neurons

Using allele-specific single-cell multi-omics sequencing, we systematically analyzed aRME in mouse olfactory sensory neurons (mOSNs), integrating allelic transcription and chromatin accessibility to mitigate data sparsity. We identified 42 aRME genes, many essential for neuronal function, and demonstrated that aRME influences gene dosage variation, exemplified by Epha7.

Notably, aRME genes overlap with dosage-sensitive genes linked to neurological disorders, suggesting their role in disease pathology.Additionally, even a single nucleotide variant between two alleles of ORs can drive significant molecular differences of OSN, supporting the hypothesis that aRME contributes to cellular and functional diversity.Our findings highlight aRME’s genome-wide distribution, its impact on gene dosage and genotype variation, and the need for caution in gene-editing therapies to avoid unintended consequences.