疾病基因組特刊以及植物表觀遺傳學

文章一（特邀綜述）

罕見基因突變在常見疾病中的作用

Lorenzo Bomba,Klaudia Walter and Nicole Soranzo

【導讀】基因型在多大程度上能決定表型？這是疾病基因組學一直致力探討的問題。然而無法迴避的困難來自於人群樣本大小、突變基因頻率所限定的統計學檢驗效能，故而低頻突變在疾病基因組的浩瀚大數據中如同宇宙暗物質一般神秘。來自英國Sanger研究所的Nicole Soranzo和她的同事們應邀為我們綜述罕見致病基因突變研究在方法學上的進展，包括全球幾大基因組資料庫建成後各個研究組在開放數據基礎上再演算而獲得的研究成果。毫無疑問，對基因相關性研究，研究人群越大越有利、功能驗證越細越有說服力，但是如何有效設計實驗得到最大效果，也許你能從這篇綜述中獲得靈感。

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（特邀綜述）

疾病的多組學研究方法

Yehudit Hasin,Marcus Seldin and Aldons Lusis

【導讀】後基因組時代的疾病基因研究給多組學合作提供一個舞台：基因組學、表觀基因組學、轉錄組學、代謝組學以及微生物組學都是疾病基因組研究不可忽視的組成部分。來自美國加州大學洛杉磯分校的Aldons Lusis研究組應邀為我們綜述搭建多組學研究的三種構架：從基因組出發、從表型出發以及從環境出發，希望能為嘗試多組學研究的學者們提供一些提示。

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（植物表觀遺傳特刊）

擬南芥核糖體RNA基因簇上位效應與等位效應的相互作用

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

【導讀】雖然核糖體RNA是主要的總RNA成分，但是大部分核糖體RNA基因在大部分時間被染色質修飾所抑制而呈靜息狀態。擬南芥的核糖體RNA基因簇主要位於2號染色體和4號染色體，因此被稱為rDNA-2和rDNA-4。本文作者利用1001Genomes Consortium的開放數據平台以及擬南芥多親本雜交群（MAGIC）取得兩個基因簇的表達特徵，再利用擬南芥個體研究便捷的優勢，在多個擬南芥亞種中選擇性抑制一簇基因，來觀察這兩個基因簇表達的上位效應與等位效應的相互作用，並發現亞種之間的表現並非一成不變的。雖然未能挖掘到這些現象背後的分子機制，本文為核糖體RNA單倍體型表達調控提供了證據。

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. InArabidopsis 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（植物表觀遺傳特刊）

植物CMT的進化和基因體DNA甲基化

Adam J. Bewick, Chad E. Niederhuth, Lexiang Ji, Nicholas A. Rohr,Patrick T. Griffin, Jim Leebens-Mack and Robert J. Schmitz

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創刊於2000年，致力於從基因組及後基因組視角涵蓋生物學和醫學生物學的所有領域。文獻類型包括 Research,Method, Software, Review, Opinion 和 Commentary。部分經常覆蓋的領域有基因序列分析，生物信息學，分子細胞生物學，功能基因組學，表觀基因組學，群體基因組學，蛋白質組學，比較生物學與進化，系統生物學，疾病基因組學和臨床基因組學。所有發表內容皆為開放獲取內容。

喜歡這篇文章嗎？立刻分享出去讓更多人知道吧！