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 hot spots 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 beb iased 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.基因的某一等位基因可通过表观遗传调控，呈现出亲本起源偏好性的表达模式，这一现象被称为基因组印记（genomic imprinting）。 基因组印记具有高度的组织特异性，而哺乳动物大脑正是该效应的活跃热点区域。 人类的社交行为缺陷与小鼠的多种行为改变均已被证实与印记异常相关，但目前学界对这类效应的发生机制与原因仍知之甚少。 大脑的嗅觉系统是介导啮齿类动物先天行为的核心感觉环路。 单等位基因表达（monoallelic expression）作为相关过程，广泛存在于化学感觉神经元中，用于调控嗅觉受体与犁鼻器受体的选择。 我们的研究数据显示，受体基因的选择并非随机过程，这意味着等位基因的选择同样可能存在偏好性。 因此，通过高分辨率RNA测序（RNA-sequencing）结合等位基因特异性转录组图谱分析，嗅觉系统是检测等位基因失衡乃至全新印记基因的理想研究靶点。 本项目旨在检测啮齿类动物关键嗅觉组织——犁鼻器（vomeronasal organ, VNO）——神经元中的亲本起源与品系起源等位基因表达偏好性。 研究人员分别从两个近交品系（C57BL/6J与CAST）的正反交F1杂交小鼠（S杂交组与M杂交组）中提取了RNA。 测序完成后，将通过比对品系特异性参考基因组中的单核苷酸多态性（SNP）与插入缺失（indel）差异，区分每个等位基因的表达水平。 本分析将与杰克逊实验室（Jackson Laboratory）的Gary Churchill团队合作开展，该团队已开发出针对CAST × C57BL/6J F1小鼠RNA-seq数据的分析方法。 后续将对存在显著且可重复等位基因失衡的基因展开研究，以评估其功能影响。