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1.  Methodology for the analysis of rare genetic variation in genome-wide association and re-sequencing studies of complex human traits 
Briefings in Functional Genomics  2014;13(5):362-370.
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’. Consequently, there has been an exciting period of research and development into the methodology for the analysis of rare genetic variants, typically by considering their joint effects on complex traits within the same functional unit or genomic region. In this review, we describe a general framework for modelling the joint effects of rare genetic variants on complex traits in association studies of unrelated individuals. We summarise a range of widely used association tests that have been developed from this model and provide an overview of the relative performance of these approaches from published simulation studies.
doi:10.1093/bfgp/elu012
PMCID: PMC4168660  PMID: 24916163
rare variant; burden test; dispersion test; statistical methodology; genome-wide association; whole-genome and whole-exome re-sequencing
2.  Structural variations in plant genomes 
Briefings in Functional Genomics  2014;13(4):296-307.
Differences between plant genomes range from single nucleotide polymorphisms to large-scale duplications, deletions and rearrangements. The large polymorphisms are termed structural variants (SVs). SVs have received significant attention in human genetics and were found to be responsible for various chronic diseases. However, little effort has been directed towards understanding the role of SVs in plants. Many recent advances in plant genetics have resulted from improvements in high-resolution technologies for measuring SVs, including microarray-based techniques, and more recently, high-throughput DNA sequencing. In this review we describe recent reports of SV in plants and describe the genomic technologies currently used to measure these SVs.
doi:10.1093/bfgp/elu016
PMCID: PMC4110416  PMID: 24907366
structural variations (SVs); next-generation sequencing (NGS); copy number variations (CNVs); presence and absence variations (PAVs); inversions; translocations
3.  TAL effectors: tools for DNA Targeting 
Briefings in Functional Genomics  2014;13(5):409-419.
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 the cognate nucleotide sequence of the sense DNA strand. Artificially designed TALE-DNA-binding domains fused to nuclease or activation and repressor domains provide an outstanding toolbox for targeted gene editing and gene regulation in research, biotechnology and gene therapy. Gene editing with custom-designed TALE nucleases (TALENs) extends the repertoire of targeted genome modifications across a broad spectrum of organisms ranging from plants and insect to mammals.
doi:10.1093/bfgp/elu013
PMCID: PMC4168661  PMID: 24907364
TALE; TALEN; ZFN; FokI; DNA editing
4.  RNAi screens to identify components of gene networks that modulate aging in Caenorhabditis elegans 
Our understanding of the genetic mechanisms of organismal aging has advanced dramatically during the past two decades. With the development of large-scale RNAi screens, the last few years saw the remarkable identifications of hundreds of new longevity genes in the roundworm Caenorhabditis elegans. The various RNAi screens revealed many biological pathways previously unknown to be related to aging. In this review, we focus on findings from the recent large-scale RNAi longevity screens, and discuss insights they have provided into the complex biological process of aging and considerations of the RNAi technology will continue to have on the future development of the aging field.
doi:10.1093/bfgp/elp051
PMCID: PMC3096447  PMID: 20053814
aging; RNAi screen; gene networks; C. elegans; lifespan
5.  Lineage-specific transcription factors and the evolution of gene regulatory networks 
Nature is replete with examples of diverse cell types, tissues and body plans, forming very different creatures from genomes with similar gene complements. However, while the genes and the structures of proteins they encode can be highly conserved, the production of those proteins in specific cell types and at specific developmental time points might differ considerably between species. A full understanding of the factors that orchestrate gene expression will be essential to fully understand evolutionary variety. Transcription factor (TF) proteins, which form gene regulatory networks (GRNs) to act in cooperative or competitive partnerships to regulate gene expression, are key components of these unique regulatory programs. Although many TFs are conserved in structure and function, certain classes of TFs display extensive levels of species diversity. In this review, we highlight families of TFs that have expanded through gene duplication events to create species-unique repertoires in different evolutionary lineages. We discuss how the hierarchical structures of GRNs allow for flexible small to large-scale phenotypic changes. We survey evidence that explains how newly evolved TFs may be integrated into an existing GRN and how molecular changes in TFs might impact the GRNs. Finally, we review examples of traits that evolved due to lineage-specific TFs and species differences in GRNs.
doi:10.1093/bfgp/elp056
PMCID: PMC3096533  PMID: 20081217
transcription factors; gene regulatory network; evolution; lineage-specific genes

Results 1-5 (5)