Briefings in Functional Genomics

http://bfg.oxfordjournals.org

List of Papers (Total 498)

Chromatin organization in pluripotent cells: emerging approaches to study and disrupt function

Translating the vast amounts of genomic and epigenomic information accumulated on the linear genome into three-dimensional models of nuclear organization is a current major challenge. In response to this challenge, recent technological innovations based on chromosome conformation capture methods in combination with increasingly powerful functional approaches have revealed...

Extracellular vesicle long noncoding RNA as potential biomarkers of liver cancer

Analysis of extracellular vesicles (EV) and their contents may be useful as disease biomarkers if they reflect the contents of cells of origin, differ between normal and diseased tissue and can be reliably detected. An increasing number of long noncoding RNA (lncRNA) are being reported to be aberrantly expressed in human cancers. These tumor-associated lncRNA may have potential...

Hypoxic regulation of the noncoding genome and NEAT1

Activation of hypoxia pathways is both associated with and contributes to an aggressive phenotype across multiple types of solid cancers. The regulation of gene transcription by hypoxia-inducible factor (HIF) is a key element in this response. HIF directly upregulates the expression of many hundreds of protein-coding genes, which act to both improve oxygen delivery and to reduce...

Efforts to make and apply humanized yeast

Despite a billion years of divergent evolution, the baker’s yeast Saccharomyces cerevisiae has long proven to be an invaluable model organism for studying human biology. Given its tractability and ease of genetic manipulation, along with extensive genetic conservation with humans, it is perhaps no surprise that researchers have been able to expand its utility by expressing human...

Building a KATalogue of acetyllysine targeting and function

Acetylation is a dynamic post-translational modification that is attached to protein substrates by lysine acetyltransferases (KATs) and removed by lysine deacetylases (KDACs). While these enzymes are best characterized as histone modifiers and regulators of gene transcription, work in a number of systems highlights that acetylation is a pervasive modification and suggests a broad...

The past, present and future of mitochondrial genomics: have we sequenced enough mtDNAs?

The year 2014 saw more than a thousand new mitochondrial genome sequences deposited in GenBank—an almost 15% increase from the previous year. Hundreds of peer-reviewed articles accompanied these genomes, making mitochondrial DNAs (mtDNAs) the most sequenced and reported type of eukaryotic chromosome. These mtDNA data have advanced a wide range of scientific fields, from forensics...

Advances in long noncoding RNAs: identification, structure prediction and function annotation

Long noncoding RNAs (lncRNAs), generally longer than 200 nucleotides and with poor protein coding potential, are usually considered collectively as a heterogeneous class of RNAs. Recently, an increasing number of studies have shown that lncRNAs can involve in various critical biological processes and a number of complex human diseases. Not only the primary sequences of many...

Evolutionary genetics of insect innate immunity

Patterns of evolution in immune defense genes help to understand the evolutionary dynamics between hosts and pathogens. Multiple insect genomes have been sequenced, with many of them having annotated immune genes, which paves the way for a comparative genomic analysis of insect immunity. In this review, I summarize the current state of comparative and evolutionary genomics of...

Double nexus—Doublesex is the connecting element in sex determination

In recent years, our knowledge of the conserved master-switch gene doublesex (dsx) and its function in regulating the development of dimorphic traits in insects has deepened considerably. Here, a comprehensive overview is given on the properties of the male- and female-specific dsx transcripts yielding DSXF and DSXM proteins in Drosophila melanogaster, and the many downstream...

Integrating evo-devo with ecology for a better understanding of phenotypic evolution

Evolutionary developmental biology (evo-devo) has provided invaluable contributions to our understanding of the mechanistic relationship between genotypic and phenotypic change. Similarly, evolutionary ecology has greatly advanced our understanding of the relationship between the phenotype and the environment. To fully understand the evolution of organismal diversity, a thorough...

Human inversions and their functional consequences

Polymorphic inversions are a type of structural variants that are difficult to analyze owing to their balanced nature and the location of breakpoints within complex repeated regions. So far, only a handful of inversions have been studied in detail in humans and current knowledge about their possible functional effects is still limited. However, inversions have been related to...

Complex and multi-allelic copy number variation in human disease

Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels—alleles...

Nuclear processes associated with plant immunity and pathogen susceptibility

Plants are sessile organisms that have evolved exquisite and sophisticated mechanisms to adapt to their biotic and abiotic environment. Plants deploy receptors and vast signalling networks to detect, transmit and respond to a given biotic threat by inducing properly dosed defence responses. Genetic analyses and, more recently, next-generation -omics approaches have allowed...

Event-based text mining for biology and functional genomics

The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information...

In vivo formaldehyde cross-linking: it is time for black box analysis

Formaldehyde cross-linking is an important component of many technologies, including chromatin immunoprecipitation and chromosome conformation capture. The procedure remains empirical and poorly characterized, however, despite a long history of its use in research. Little is known about the specificity of in vivo cross-linking, its efficiency and chemical adducts induced by the...

Measuring differential gene expression with RNA-seq: challenges and strategies for data analysis

RNA-seq is a methodology for RNA profiling based on next-generation sequencing that enables to measure and compare gene expression patterns at unprecedented resolution. Although the appealing features of this technique have promoted its application to a wide panel of transcriptomics studies, the fast-evolving nature of experimental protocols and computational tools challenges the...

Biochemical and bioinformatic methods for elucidating the role of RNA–protein interactions in posttranscriptional regulation

Our understanding of transcriptional gene regulation has dramatically increased over the past decades, and many regulators of gene expression, such as transcription factors, have been analyzed extensively. Additionally, in recent years, deeper insights into the physiological roles of RNA have been obtained. More precisely, splicing, polyadenylation, various modifications...

High-throughput characterization of protein–RNA interactions

RNA-binding proteins (RBPs) are important regulators of eukaryotic gene expression. Genomes typically encode dozens to hundreds of proteins containing RNA-binding domains, which collectively recognize diverse RNA sequences and structures. Recent advances in high-throughput methods for assaying the targets of RBPs in vitro and in vivo allow large-scale derivation of RNA-binding...

Evolving insights on how cytosine methylation affects protein–DNA binding

Many anecdotal observations exist of a regulatory effect of DNA methylation on gene expression. However, in general, the underlying mechanisms of this effect are poorly understood. In this review, we summarize what is currently known about how this important, but mysterious, epigenetic mark impacts cellular functions. Cytosine methylation can abrogate or enhance interactions with...

Fungal cellulose degradation by oxidative enzymes: from dysfunctional GH61 family to powerful lytic polysaccharide monooxygenase family

Our understanding of fungal cellulose degradation has shifted dramatically in the past few years with the characterization of a new class of secreted enzymes, the lytic polysaccharide monooxygenases (LPMO). After a period of intense research covering structural, biochemical, theoretical and evolutionary aspects, we have a picture of them as wedge-like copper-dependent...

Elucidation of primary metabolic pathways in Aspergillus species: Orphaned research in characterizing orphan genes

Primary metabolism affects all phenotypical traits of filamentous fungi. Particular examples include reacting to extracellular stimuli, producing precursor molecules required for cell division and morphological changes as well as providing monomer building blocks for production of secondary metabolites and extracellular enzymes. In this review, all annotated genes from four...

TAL effectors: tools for DNA Targeting

Xanthomonas phytopathogenic bacteria produce unique transcription activator-like effector (TALE) proteins that recognize and activate specific plant promoters through a set of tandem repeats. A unique TALE-DNA-binding code uses two polymorphic amino acids in each repeat to mediate recognition of specific nucleotides. The order of repeats determines effector’s specificity toward...

Using population isolates in genetic association studies

The use of genetically isolated populations can empower next-generation association studies. In this review, we discuss the advantages of this approach and review study design and analytical considerations of genetic association studies focusing on isolates. We cite successful examples of using population isolates in association studies and outline potential ways forward.

Methodology for the analysis of rare genetic variation in genome-wide association and re-sequencing studies of complex human traits

Genome-wide association studies have been successful in identifying common variants that impact complex human traits and diseases. However, despite this success, the joint effects of these variants explain only a small proportion of the genetic variance in these phenotypes, leading to speculation that rare genetic variation might account for much of the ‘missing heritability...

How important are rare variants in common disease?

Genome-wide association studies have uncovered hundreds of common genetic variants involved in complex diseases. However, for most complex diseases, these common genetic variants only marginally contribute to disease susceptibility. It is now argued that rare variants located in different genes could in fact play a more important role in disease susceptibility than common...