March 4, 2010
Publication Date: 2010 Mar PMID: 20051985
Authors: Presgraves, D. C.
Journal: Nat Rev Genet
All plant and animal species arise by speciation - the evolutionary splitting of one species into two reproductively incompatible species. But until recently our understanding of the molecular genetic details of speciation was slow in coming and largely limited to Drosophila species. Here, I review progress in determining the molecular identities and evolutionary histories of several new 'speciation genes' that cause hybrid dysfunction between species of yeast, flies, mice and plants. The new work suggests that, surprisingly, the first steps in the evolution of hybrid dysfunction are not necessarily adaptive.
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Authors: Presgraves, D. C.
Journal: Nat Rev Genet
All plant and animal species arise by speciation - the evolutionary splitting of one species into two reproductively incompatible species. But until recently our understanding of the molecular genetic details of speciation was slow in coming and largely limited to Drosophila species. Here, I review progress in determining the molecular identities and evolutionary histories of several new 'speciation genes' that cause hybrid dysfunction between species of yeast, flies, mice and plants. The new work suggests that, surprisingly, the first steps in the evolution of hybrid dysfunction are not necessarily adaptive.
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February 28, 2010
Publication Date: 2010 Feb 23 PMID: 20177425
Authors: Hyduke, D. R. - Palsson, B. O.
Journal: Nat Rev Genet
Biological signalling networks allow living organisms to issue an integrated response to current conditions and make limited predictions about future environmental changes. Small-scale dynamic models of signalling cascades, including mitogen-activated protein kinase cascades, have been developed to generate hypotheses about signal transduction. Owing to technical limitations, these models and the hypotheses they generate have focused on a limited subset of signalling molecules. Now that we can simultaneously measure a substantial portion of the molecular components of a cell, we can begin to develop and test systems-level models of cellular signalling and regulatory processes, therefore gaining insights into the 'thought' processes of a cell.
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Authors: Hyduke, D. R. - Palsson, B. O.
Journal: Nat Rev Genet
Biological signalling networks allow living organisms to issue an integrated response to current conditions and make limited predictions about future environmental changes. Small-scale dynamic models of signalling cascades, including mitogen-activated protein kinase cascades, have been developed to generate hypotheses about signal transduction. Owing to technical limitations, these models and the hypotheses they generate have focused on a limited subset of signalling molecules. Now that we can simultaneously measure a substantial portion of the molecular components of a cell, we can begin to develop and test systems-level models of cellular signalling and regulatory processes, therefore gaining insights into the 'thought' processes of a cell.
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February 25, 2010
Publication Date: 2010 Feb 23 PMID: 20177426
Authors: La Spada, A. R. - Taylor, J. P.
Journal: Nat Rev Genet
Repeat expansion mutations cause at least 22 inherited neurological diseases. The complexity of repeat disease genetics and pathobiology has revealed unexpected shared themes and mechanistic pathways among the diseases, such as RNA toxicity. Also, investigation of the polyglutamine diseases has identified post-translational modification as a key step in the pathogenic cascade and has shown that the autophagy pathway has an important role in the degradation of misfolded proteins - two themes that are likely to be relevant to the entire neurodegeneration field. Insights from repeat disease research are catalysing new lines of study that should not only elucidate molecular mechanisms of disease but also highlight opportunities for therapeutic intervention for these currently untreatable disorders.
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Authors: La Spada, A. R. - Taylor, J. P.
Journal: Nat Rev Genet
Repeat expansion mutations cause at least 22 inherited neurological diseases. The complexity of repeat disease genetics and pathobiology has revealed unexpected shared themes and mechanistic pathways among the diseases, such as RNA toxicity. Also, investigation of the polyglutamine diseases has identified post-translational modification as a key step in the pathogenic cascade and has shown that the autophagy pathway has an important role in the degradation of misfolded proteins - two themes that are likely to be relevant to the entire neurodegeneration field. Insights from repeat disease research are catalysing new lines of study that should not only elucidate molecular mechanisms of disease but also highlight opportunities for therapeutic intervention for these currently untreatable disorders.
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February 21, 2010
Publication Date: 2010 Mar PMID: 20168297
Authors: Paigen, K. - Petkov, P.
Journal: Nat Rev Genet
Recombination, together with mutation, generates the raw material of evolution, is essential for reproduction and lies at the heart of all genetic analysis. Recent advances in our ability to construct genome-scale, high-resolution recombination maps and new molecular techniques for analysing recombination products have substantially furthered our understanding of this important biological phenomenon in humans and mice: from describing the properties of recombination hot spots in male and female meiosis to the recombination landscape along chromosomes. This progress has been accompanied by the identification of trans-acting systems that regulate the location and relative activity of individual hot spots.
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Authors: Paigen, K. - Petkov, P.
Journal: Nat Rev Genet
Recombination, together with mutation, generates the raw material of evolution, is essential for reproduction and lies at the heart of all genetic analysis. Recent advances in our ability to construct genome-scale, high-resolution recombination maps and new molecular techniques for analysing recombination products have substantially furthered our understanding of this important biological phenomenon in humans and mice: from describing the properties of recombination hot spots in male and female meiosis to the recombination landscape along chromosomes. This progress has been accompanied by the identification of trans-acting systems that regulate the location and relative activity of individual hot spots.
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February 20, 2010
Publication Date: 2010 Feb PMID: 20084087
Authors: Teo, Y. Y. - Small, K. S. - Kwiatkowski, D. P.
Journal: Nat Rev Genet
Medical research in Africa has yet to benefit from the advent of genome-wide association (GWA) analysis, partly because the genotyping tools and statistical methods that have been developed for European and Asian populations struggle to deal with the high levels of genome diversity and population structure in Africa. However, the haplotypic diversity of African populations might help to overcome one of the major roadblocks in GWA research, the fine mapping of causal variants. We review the methodological challenges and consider how GWA studies in Africa will be transformed by new approaches in statistical imputation and large-scale genome sequencing.
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Authors: Teo, Y. Y. - Small, K. S. - Kwiatkowski, D. P.
Journal: Nat Rev Genet
Medical research in Africa has yet to benefit from the advent of genome-wide association (GWA) analysis, partly because the genotyping tools and statistical methods that have been developed for European and Asian populations struggle to deal with the high levels of genome diversity and population structure in Africa. However, the haplotypic diversity of African populations might help to overcome one of the major roadblocks in GWA research, the fine mapping of causal variants. We review the methodological challenges and consider how GWA studies in Africa will be transformed by new approaches in statistical imputation and large-scale genome sequencing.
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February 16, 2010
Publication Date: 2010 Feb 2 PMID: 20125085
Authors: Marraffini, L. A. - Sontheimer, E. J.
Journal: Nat Rev Genet
Sequence-directed genetic interference pathways control gene expression and preserve genome integrity in all kingdoms of life. The importance of such pathways is highlighted by the extensive study of RNA interference (RNAi) and related processes in eukaryotes. In many bacteria and most archaea, clustered, regularly interspaced short palindromic repeats (CRISPRs) are involved in a more recently discovered interference pathway that protects cells from bacteriophages and conjugative plasmids. CRISPR sequences provide an adaptive, heritable record of past infections and express CRISPR RNAs - small RNAs that target invasive nucleic acids. Here, we review the mechanisms of CRISPR interference and its roles in microbial physiology and evolution. We also discuss potential applications of this novel interference pathway.
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Authors: Marraffini, L. A. - Sontheimer, E. J.
Journal: Nat Rev Genet
Sequence-directed genetic interference pathways control gene expression and preserve genome integrity in all kingdoms of life. The importance of such pathways is highlighted by the extensive study of RNA interference (RNAi) and related processes in eukaryotes. In many bacteria and most archaea, clustered, regularly interspaced short palindromic repeats (CRISPRs) are involved in a more recently discovered interference pathway that protects cells from bacteriophages and conjugative plasmids. CRISPR sequences provide an adaptive, heritable record of past infections and express CRISPR RNAs - small RNAs that target invasive nucleic acids. Here, we review the mechanisms of CRISPR interference and its roles in microbial physiology and evolution. We also discuss potential applications of this novel interference pathway.
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February 15, 2010
Publication Date: 2010 Feb 2 PMID: 20125086
Authors: Laird, P. W.
Journal: Nat Rev Genet
Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. Therefore, profiling DNA methylation across the genome is vital to understanding the influence of epigenetics. There has been a revolution in DNA methylation analysis technology over the past decade: analyses that previously were restricted to specific loci can now be performed on a genome-scale and entire methylomes can be characterized at single-base-pair resolution. However, there is such a diversity of DNA methylation profiling techniques that it can be challenging to select one. This Review discusses the different approaches and their relative merits and introduces considerations for data analysis.
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Authors: Laird, P. W.
Journal: Nat Rev Genet
Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. Therefore, profiling DNA methylation across the genome is vital to understanding the influence of epigenetics. There has been a revolution in DNA methylation analysis technology over the past decade: analyses that previously were restricted to specific loci can now be performed on a genome-scale and entire methylomes can be characterized at single-base-pair resolution. However, there is such a diversity of DNA methylation profiling techniques that it can be challenging to select one. This Review discusses the different approaches and their relative merits and introduces considerations for data analysis.
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February 14, 2010
Publication Date: 2010 Feb 9 PMID: 20142834
Authors: Law, J. A. - Jacobsen, S. E.
Journal: Nat Rev Genet
Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse biological processes, including gene and transposon silencing, imprinting and X chromosome inactivation. Recent findings in plants and animals have greatly increased our understanding of the pathways used to accurately target, maintain and modify patterns of DNA methylation and have revealed unanticipated mechanistic similarities between these organisms. Key roles have emerged for small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases in these processes. Drawing on insights from both plants and animals should deepen our understanding of the regulation and biological significance of DNA methylation.
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Authors: Law, J. A. - Jacobsen, S. E.
Journal: Nat Rev Genet
Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse biological processes, including gene and transposon silencing, imprinting and X chromosome inactivation. Recent findings in plants and animals have greatly increased our understanding of the pathways used to accurately target, maintain and modify patterns of DNA methylation and have revealed unanticipated mechanistic similarities between these organisms. Key roles have emerged for small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases in these processes. Drawing on insights from both plants and animals should deepen our understanding of the regulation and biological significance of DNA methylation.
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