Latest Articles Include:
- From the editors
- Nat Rev Genet 11(7):451 (2010)
'Omics' is in the eye of the beholder 'Omics' technologies are transforming many subfields of genetics, but their success depends on interesting hypotheses and good scientific judgement. - Functional genomics: One gene or two?
Casci T - Nat Rev Genet 11(7):453 (2010)
Variation in gene copy number is seen among species, individuals and cell types and makes an important contribution to cell and organismal fitness. Three studies have shed some light on the complicated relationship between gene dosage and protein expression levels, function and disease. - Technology: DNA methylation while you sequence
Muers M - Nat Rev Genet 11(7):454 (2010)
Genome-wide maps of DNA methylation are likely to lead to a better understanding of the functions of this epigenetic modification, but the current nucleotide-resolution method of sequencing bisulphite-treated DNA has several technical limitations. Now, a high-throughput technique that detects methylation and the primary DNA sequence at the same time offers the exciting possibility of mapping different types of methylation without the need for complex sample preparation and alignment to a reference genome. - Transcription: Shadow enhancers confer robustness
Swami M - Nat Rev Genet 11(7):454 (2010)
Many developmental genes contain multiple enhancers that drive apparently redundant patterns of transcription, but what are the functions of these various regulatory elements? A new study in Drosophila species indicates that secondary, 'shadow' enhancers, which are distant from promoter regions, confer phenotypic robustness to environmental and genetic perturbations. Frankel, Stern and colleagues identified two secondary enhancers (Z and DG2) that lie upstream of three known enhancers in the shavenbaby (svb) gene, which encodes a transcription factor. - In brief: Mutagenesis, Evolution, Genetic variation, Development
- Nat Rev Genet 11(7):454 (2010)
Mutagenesis Generating knockout rats by transposon mutagenesis in spermatogonial stem cells Izsvák, Z. et al. Nature Methods 7, 443â€"445 (2010) A high-throughput method for generating targeted mutations in rats is an important advance for using these organisms for functional genomics. The Sleeping Beauty transposon system was used to knock out genes in rat spermatogonial stem cells. - Transcriptomics: Throwing light on dark matter
- Nat Rev Genet 11(7):455 (2010)
Reports over the past few years of extensive transcription throughout eukaryotic genomes have led to considerable excitement. But doubts have been raised about the methods that have detected this pervasive transcription and about how much of it is functional. - Mutation: It's the CpG content that counts
Swami M - Nat Rev Genet 11(7):456 (2010)
The rate of neutral mutations â€" those that are not subject to natural selection â€" shows substantial variation, but the factors contributing to mutational rate have remained elusive. Now, new evidence indicates that the CpG content of DNA can even influence the mutation rate of non-CpG-containing sequences, suggesting that intrinsic properties of DNA sequences may be more important than the chromosomal environment in determining mutation rates and genome integrity. - Genomics: Technical feat gives clues to human origins
Casci T - Nat Rev Genet 11(7):456 (2010)
The long-awaited genome sequence of our closest evolutionary relative has now been completed. The Neanderthal genome, which was sequenced at 1.3-fold coverage by stitching together 4 billion nucleotides of shotgun fragments, paints a revised picture of the evolutionary relationship with our ancient cousins. - In brief: Stem cells, Plant genetics, Genome evolution, Population genomics
- Nat Rev Genet 11(7):456 (2010)
Stem cells Functional heterogeneity of embryonic stem cells revealed through translational amplification of an early endodermal transcript Canham, M. A. et al. PLoS Biol. 8, e1000379 (2010) Mouse embryonic stem (ES) cells are generally thought not to contribute to extra-embryonic lineages in chimaera experiments. - Epigenomics: Catching nucleosomes in action
Muers M - Nat Rev Genet 11(7):457 (2010)
Techniques such as chromatin immunoprecipitation have enabled great advances through providing 'snapshots' of the epigenome, but it remains technically difficult to study the dynamics of nucleosome turnover. A new method that directly assays native histone turnover shows great promise and has already challenged models of epigenetic maintenance. - New approaches to population stratification in genome-wide association studies
Price AL Zaitlen NA Reich D Patterson N - Nat Rev Genet 11(7):459 (2010)
Genome-wide association (GWA) studies are an effective approach for identifying genetic variants associated with disease risk. GWA studies can be confounded by population stratification — systematic ancestry differences between cases and controls — which has previously been addressed by methods that infer genetic ancestry. Those methods perform well in data sets in which population structure is the only kind of structure present but are inadequate in data sets that also contain family structure or cryptic relatedness. Here, we review recent progress on methods that correct for stratification while accounting for these additional complexities. systematic ancestry differences between cases and controls — which has previously been addressed by methods that infer genetic ancestry. Those methods perform well in data sets in which population structure is the only kind of structure present but are inadequate in data sets that also contain family structure or cryptic rel! atedness. Here, we review recent progress on methods that correct for stratification while accounting for these additional complexities. - Evolutionary microbial genomics: insights into bacterial host adaptation
Toft C Andersson SG - Nat Rev Genet 11(7):465 (2010)
Host-adapted bacteria include mutualists and pathogens of animals, plants and insects. Their study is therefore important for biotechnology, biodiversity and human health. The recent rapid expansion in bacterial genome data has provided insights into the adaptive, diversifying and reductive evolutionary processes that occur during host adaptation. The results have challenged many pre-existing concepts built from studies of laboratory bacterial strains. Furthermore, recent studies have revealed genetic changes associated with transitions from parasitism to mutualism and opened new research avenues to understand the functional reshaping of bacteria as they adapt to growth in the cytoplasm of a eukaryotic host. - Next-generation genomics: an integrative approach
Hawkins RD Hon GC Ren B - Nat Rev Genet 11(7):476 (2010)
Integrating results from diverse experiments is an essential process in our effort to understand the logic of complex systems, such as development, homeostasis and responses to the environment. With the advent of high-throughput methods — including genome-wide association (GWA) studies, chromatin immunoprecipitation followed by sequencing (ChIP–seq) and RNA sequencing (RNA–seq) — acquisition of genome-scale data has never been easier. Epigenomics, transcriptomics, proteomics and genomics each provide an insightful, and yet one-dimensional, view of genome function; integrative analysis promises a unified, global view. However, the large amount of information and diverse technology platforms pose multiple challenges for data access and processing. This Review discusses emerging issues and strategies related to data integration in the era of next-generation genomics. - Constraints and plasticity in genome and molecular-phenome evolution
Koonin EV Wolf YI - Nat Rev Genet 11(7):487 (2010)
Multiple constraints variously affect different parts of the genomes of diverse life forms. The selective pressures that shape the evolution of viral, archaeal, bacterial and eukaryotic genomes differ markedly, even among relatively closely related animal and bacterial lineages; by contrast, constraints affecting protein evolution seem to be more universal. The constraints that shape the evolution of genomes and phenomes are complemented by the plasticity and robustness of genome architecture, expression and regulation. Taken together, these findings are starting to reveal complex networks of evolutionary processes that must be integrated to attain a new synthesis of evolutionary biology. - Genotype imputation for genome-wide association studies
Marchini J Howie B - Nat Rev Genet 11(7):499 (2010)
In the past few years genome-wide association (GWA) studies have uncovered a large number of convincingly replicated associations for many complex human diseases. Genotype imputation has been used widely in the analysis of GWA studies to boost power, fine-map associations and facilitate the combination of results across studies using meta-analysis. This Review describes the details of several different statistical methods for imputing genotypes, illustrates and discusses the factors that influence imputation performance, and reviews methods that can be used to assess imputation performance and test association at imputed SNPs. - Yeast evolutionary genomics
- Nat Rev Genet 11(7):512 (2010)
Over the past few years, genome sequences have become available from an increasing range of yeast species, which has led to notable advances in our understanding of evolutionary mechanisms in eukaryotes. Yeasts offer us a unique opportunity to examine how molecular and reproductive mechanisms combine to affect genome architectures and drive evolutionary changes over a broad range of species. This Review summarizes recent progress in understanding the molecular mechanisms — such as gene duplication, mutation and acquisition of novel genetic material — that underlie yeast evolutionary genomics. I also discuss how results from yeasts can be extended to other eukaryotes.
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