Identification of imprinted genes, demonstrating a consistent preference towards the paternal or maternal allelic expression, is important for the understanding of gene expression regulation during embryonic development and of the molecular basis of developmental disorders with a parent-of-origin effect. Combining allelic analysis of RNA-Seq data with phased genotypes in family trios provides a powerful method to detect parent-of-origin biases in gene expression. We report findings in 296 family trios from two large studies: 165 lymphoblastoid cell lines from the 1000 Genomes Project and 131 blood samples from the Genome of the Netherlands (GoNL) participants. Based on parental haplotypes, we identified > 2.8 million transcribed heterozygous SNVs phased for parental origin and developed a robust statistical framework for measuring allelic expression. We identified a total of 45 imprinted genes and one imprinted unannotated transcript, including multiple imprinted transcripts showing incomplete parental expression bias that was located adjacent to strongly imprinted genes. For example, PXDC1, a gene which lies adjacent to the paternally expressed gene FAM50B, shows a 2:1 paternal expression bias. Other imprinted genes had promoter regions that coincide with sites of parentally biased DNA methylation identified in the blood from uniparental disomy (UPD) samples, thus providing independent validation of our results. Using the stranded nature of the RNA-Seq data in lymphoblastoid cell lines, we identified multiple loci with overlapping sense/antisense transcripts, of which one is expressed paternally and the other maternally. Using a sliding window approach, we searched for imprinted expression across the entire genome, identifying a novel imprinted putative lncRNA in 13q21.2. Overall, we identified 7 transcripts showing parental bias in gene expression which were not reported in 4 other recent RNA-Seq studies of imprinting. Our methods and data provide a robust and high-resolution map of imprinted gene expression in the human genome.

中文翻译：

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296 个定相三重奏中的 RNA-Seq 提供了基因组印记的高分辨率图谱。


印记基因的鉴定，证明对父本或母本等位基因表达的一致偏好，对于理解胚胎发育过程中的基因表达调控以及具有亲本效应的发育障碍的分子基础非常重要。将 RNA-Seq 数据的等位基因分析与家族三重奏中的阶段性基因型相结合，提供了一种检测基因表达中亲本偏差的强大方法。我们报告了两项大型研究中 296 个家庭三人组的结果：来自 1000 个基因组计划的 165 个类淋巴母细胞系和来自荷兰基因组 (GoNL) 参与者的 131 个血液样本。基于亲本单倍型，我们鉴定了 > 280 万个转录杂合 SNV，这些 SNV 分相为亲本起源，并开发了一个用于测量等位基因表达的强大统计框架。我们总共鉴定了 45 个印记基因和一个印记未注释转录本，其中包括位于强印记基因附近的多个显示不完全亲本表达偏差的印记转录本。例如，PXDC1（与父本表达基因 FAM50B 相邻的基因）显示出 2:1 的父本表达偏向。其他印记基因的启动子区域与单亲二倍体 (UPD) 样本血液中发现的亲本偏向 DNA 甲基化位点一致，从而为我们的结果提供了独立验证。利用类淋巴母细胞系中RNA-Seq数据的搁浅性质，我们鉴定了具有重叠有义/反义转录本的多个位点，其中一个在父系表达，另一个在母系表达。 使用滑动窗口方法，我们在整个基因组中搜索印记表达，在 13q21.2 中识别出一种新的印记推定 lncRNA。总体而言，我们鉴定了 7 个转录本，这些转录本在基因表达方面显示出亲代偏见，而这些转录本在最近的其他 4 项印迹 RNA-Seq 研究中并未报告。我们的方法和数据提供了人类基因组中印记基因表达的可靠且高分辨率的图谱。