Parent_of_origin_allelic_expression_bias_in_mouse_vomernasal_organ-sc-3262
Parent_of_origin_allelic_expression_bias_in_mouse_vomernasal_organ
An allele of a gene can be epigenetically regulated to show a parent-of-origin biased expression pattern, a phenomenon referring to as genomic imprinting. Genomic imprinting is highly tissue-specific, and mammalian brains are hotspots for this effect. Social behaviour defects in human and various behavioural changes in mouse, had been linked to inappropriate imprinting, but little is known about how and why such effects occur.  The olfactory system in the brain is the essential sensory circuitry that mediates rodent innate behaviour. Meanwhile, monoallelic expression, a related process, is used extensively in chemosensory neurons to regulate olfactory and vomeronasal receptor choice. We have data showing receptor gene choice is not a random process, which implies allele choice may be biased also. The olfactory system is therefore a promising target for detecting allelic imbalance, or even novel imprinting genes, by high-resolution RNA-sequencing followed by allelic-specific transcriptomic mapping.  This project is designed to detect parent-of-origin and strain-of-origin allelic expression bias in neurons from a key olfactory tissues in rodents: vomernasal organ (VNO) . RNA from reciprocally crossed F1 hybrid mice (S-cross and M-cross) from two distinct inbred strains (C57BL/6J and CAST) have been extracted respectively. After sequencing, expression levels from each allele will be distinguished by incorporating SNP and indel differences to the strain-specific reference genomes. Analysis will be carried out in collaboration with Gary Churchill's team at the Jackson Laboratory (who have developed a method of analysing RNAseq data from CAST x C57BL/6J F1s).Genes with strong, reproducible allelic imbalances will be followed up to assess the functional consequences.
Genomic imprinting is the significant expression bias between paternally- and maternallyderived alleles. It happens more often in the brain and is known to influence behaviour in mouse and human. Sensory neurons in the olfactory system are promising and unexplored targets of this effect and may lead to detectable functional changes in behaviour. We have isolated RNAs from a key olfaction tissue in rodents: vomernasal organ (VNO), in the female mice of two reciprocally crossed F1 hybrids: CAST/EiJ x C57BL/6J and C57BL/6J x CAST/EiJ. We expect to detect expression differences between paternally and maternally inherited alleles in these tissues by RNA sequencing followed by allelicspecially transcriptomic mapping using SNPs and indels differences in strain-specific genomes.