本文经授权转载自微信公众号“BioMedCentral开放获取出版”（ID: BMC2000）
文章一（特邀综述）
罕见基因突变在常见疾病中的作用
The impact of rare and low-frequency genetic variants in common disease
Lorenzo Bomba,Klaudia Walter and Nicole Soranzo
【导读】基因型在多大程度上能决定表型？这是疾病基因组学一直致力探讨的问题。然而无法回避的困难来自于人群样本大小、突变基因频率所限定的统计学检验效能，故而低频突变在疾病基因组的浩瀚大数据中如同宇宙暗物质一般神秘。来自英国Sanger研究所的Nicole Soranzo和她的同事们应邀为我们综述罕见致病基因突变研究在方法学上的进展，包括全球几大基因组数据库建成后各个研究组在开放数据基础上再演算而获得的研究成果。毫无疑问，对基因相关性研究，研究人群越大越有利、功能验证越细越有说服力，但是如何有效设计实验得到最大效果，也许你能从这篇综述中获得灵感。
Abstract
Despite thousands of genetic loci identified to date, alarge proportion of genetic variation predisposing to complex disease and traits remains unaccounted for. Advances in sequencing technology enable focused explorations on the contribution of low-frequency and rare variants to human traits. Here we review experimental approaches and current knowledge on the contribution of these genetic variants in complex disease and discuss challenges and opportunities for personalised medicine.
文章二（特邀综述）
疾病的多组学研究方法
Multi-omics approaches to disease
Yehudit Hasin,Marcus Seldin and Aldons Lusis
【导读】后基因组时代的疾病基因研究给多组学合作提供一个舞台：基因组学、表观基因组学、转录组学、代谢组学以及微生物组学都是疾病基因组研究不可忽视的组成部分。来自美国加州大学洛杉矶分校的Aldons Lusis研究组应邀为我们综述搭建多组学研究的三种构架：从基因组出发、从表型出发以及从环境出发，希望能为尝试多组学研究的学者们提供一些提示。
Abstract
High-throughput technologies have revolutionized medical research. The advent of geno typing arrays enabled large-scale genome-wide association studies and methods for examining global transcript levels, which gave rise to the field of “integrative genetics”. Other omics technologies,such as proteomics and metabolomics, are now often incorporated into the everyday methodology of biological researchers. In this review, we provide an overview of such omics technologies and focus on methods for their integration across multiple omics layers. As compared to studies of a single omics type,multi-omics offers the opportunity to understand the flow of information that underlies disease
文章三（植物表观遗传特刊）
拟南芥核糖体RNA基因簇上位效应与等位效应的相互作用
Epistatic and allelic interactions control expression of ribosomal RNA gene clusters in Arabidopsis thaliana
Fernando A. Rabanal Terezie Mandáková, Luz M. Soto-Jiménez,Robert Greenhalgh, David L. Parrott, Stefan Lutzmayer, Joshua G. Steffen,Viktoria Nizhynska, Richard Mott, Martin A. Lysak, Richard M. Clark andMagnus Nordborg
【导读】虽然核糖体RNA是主要的总RNA成分，但是大部分核糖体RNA基因在大部分时间被染色质修饰所抑制而呈静息状态。拟南芥的核糖体RNA基因簇主要位于2号染色体和4号染色体，因此被称为rDNA-2和rDNA-4。本文作者利用1001Genomes Consortium的开放数据平台以及拟南芥多亲本杂交群（MAGIC）取得两个基因簇的表达特征，再利用拟南芥个体研究便捷的优势，在多个拟南芥亚种中选择性抑制一簇基因，来观察这两个基因簇表达的上位效应与等位效应的相互作用，并发现亚种之间的表现并非一成不变的。虽然未能挖掘到这些现象背后的分子机制，本文为核糖体RNA单倍体型表达调控提供了证据。
Abstract
Background: Ribosomal RNA (rRNA) accounts for the majority of the RNA in eukaryotic cells, and is encoded by hundreds to thousands of nearly identical gene copies, only a subset of which are active at any given time. In Arabidopsis thaliana, 45S rRNA genes are found in two large ribosomal DNA (rDNA) clusters and little is known about the contribution of each to the overall transcription pattern in the species.
Results: By taking advantage of genome sequencing data from the 1001 Genomes Consortium, we characterize rRNA gene sequence variation within and among accessions. Notably, variation is not restricted to thepre-rRNA sequences removed during processing, but it is also present within the highly conserved ribosomal subunits. Through linkage mapping we assign the sevariants to a particular rDNA cluster unambiguously and use them as reporters of rDNA cluster-specific expression. We demonstrate that rDNA cluster-usagevaries greatly among accessions and that rDNA cluster-specific expression and silencing is controlled via genetic interactions between entire rDNA clusterhaplotypes (alleles).
Conclusions: We show that rRNA gene cluster expression is controlled via complex epistatic and allelic interactions between rDNA haplotypes that apparently regulate the entire rRNA gene cluster. Furthermore,the sequence polymorphism we discovered implies that the pool of rRNA in a cell may be heterogeneous, which could have functional consequences.
文章四（植物表观遗传特刊）
植物CMT的进化和基因体DNA甲基化
The evolution of CHROMOMETHYLASES and gene body DNA methylation in plants
Adam J. Bewick, Chad E. Niederhuth, Lexiang Ji, Nicholas A. Rohr,Patrick T. Griffin, Jim Leebens-Mack and Robert J. Schmitz
【导读】CMT是一组在多物种间相对保守的胞嘧啶甲基转移酶，广泛存在于陆地植物和藻类。由共有的染色质组织修饰蛋白域（CHRromatinOrganisation MOdifier）而得名。本文作者利用1KP Consortium (www.onekp.com)的多组学数据，包括一千多个转录组和77个甲基化组学数据，分析CMT在植物届的进化，并阐述基因体的DNA甲基化是如何受CMT进化的影响。
Abstract
Background:The evolution of gene body methylation (gbM), its origins, and its functional consequences are poorly understood. By pairing the largest collection of transcriptomes (>1000) and methylomes (77) across Viridiplantae, we provide novel insights into the evolution of gbM and its relationship to CHROMOMETHYLASE (CMT) proteins.
Results:CMTs are evolutionary conserved DNA methyltransferases in Viridiplantae. Duplication events gave rise to what are now referred to as CMT1, 2 and 3. Independent losses of CMT1, 2, and 3 ineudicots, CMT2 and ZMET in monocots and monocots/commelinids, variation in copy number, and non-neutral evolution suggests overlapping or fluid functional evolution of this gene family. DNA methylation within genes is widespread and is found in all major taxonomic groups of Viridiplantae investigated. Genes enriched with methylated CGs (mCG) were also identified in species sister to angiosperms. The proportion of genes and DNA methylation patterns associated with gbM are restricted to angiosperms with a functional CMT3 or ortholog.However, mCG-enriched genes in the gymnosperm Pinus taeda sharedsome similarities with gbM genes in Amborella trichopoda.Additionally, gymnosperms and ferns share a CMT homolog closely related to CMT2and 3. Hence, the dependency of gbM on a CMT most likely extends to all angiosperms and possibly gymnosperms and ferns.
Conclusions:The resulting gene family phylogeny of CMT transcripts from the most diverse sampling of plants to date redefines our understanding of CMT evolution and its evolutionary consequences on DNA methylation. Future, functional tests of homologous and paralogous CMTs willuncover novel roles and consequences to the epigenome.
Genome Biology 创刊于2000年，致力于从基因组及后基因组视角涵盖生物学和医学生物学的所有领域。文献类型包括 Research,Method, Software, Review, Opinion 和 Commentary。部分经常覆盖的领域有基因序列分析，生物信息学，分子细胞生物学，功能基因组学，表观基因组学，群体基因组学，蛋白质组学，比较生物学与进化，系统生物学，疾病基因组学和临床基因组学。所有发表内容皆为开放获取内容。
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