The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a ...genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting.
High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments ...have focused on specific biological processes and perturbations. Here, we have generated and analyzed gene expression from a set of samples spanning a broad range of biological conditions. Specifically, we profiled gene expression from 91 human and mouse samples across a diverse array of tissues, organs, and cell lines. Because these samples predominantly come from the normal physiological state in the human and mouse, this dataset represents a preliminary, but substantial, description of the normal mammalian transcriptome. We have used this dataset to illustrate methods of mining these data, and to reveal insights into molecular and physiological gene function, mechanisms of transcriptional regulation, disease etiology, and comparative genomics. Finally, to allow the scientific community to use this resource, we have built a free and publicly accessible website (http://expression.gnf.org) that integrates data visualization and curation of current gene annotations.
Genome-wide gene expression profiling has been extensively used to generate biological hypotheses based on differential expression. Recently, many studies have used microarrays to measure gene ...expression levels across genetic mapping populations. These gene expression phenotypes have been used for genome-wide association analyses, an analysis referred to as expression QTL (eQTL) mapping. Here, eQTL analysis was performed in adipose tissue from 28 inbred strains of mice. We focused our analysis on "trans-eQTL bands", defined as instances in which the expression patterns of many genes were all associated to a common genetic locus. Genes comprising trans-eQTL bands were screened for enrichments in functional gene sets representing known biological pathways, and genes located at associated trans-eQTL band loci were considered candidate transcriptional modulators. We demonstrate that these patterns were enriched for previously characterized relationships between known upstream transcriptional regulators and their downstream target genes. Moreover, we used this strategy to identify both novel regulators and novel members of known pathways. Finally, based on a putative regulatory relationship identified in our analysis, we identified and validated a previously uncharacterized role for cyclin H in the regulation of oxidative phosphorylation. We believe that the specific molecular hypotheses generated in this study will reveal many additional pathway members and regulators, and that the analysis approaches described herein will be broadly applicable to other eQTL data sets.
We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs ...isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.
Two conservation strategies have been put in place in Europe to address precipitous population declines of wading birds that breed on lowland wet grasslands. These are site protection and ...agri‐environment schemes (AESs) and the two are rarely compared, or their synergy assessed. Increasingly, efforts to recover populations of previously widespread species follow a landscape‐scale approach whereby habitat improvement takes place at key sites through partially overlapping protected area management and AESs. To investigate whether site protection and AESs improve the conservation status of breeding waders and how these interact, we partially repeated a 2002 survey of breeding waders on protected areas (nature reserves and Sites of Special Scientific Interest) and sites with wader‐specific AES options in England in 2009 and 2010. We then assessed the individual and combined effects of these delivery mechanisms on field occupancy, breeding density and population change of four species of declining wader (Northern Lapwing Vanellus vanellus, Common Snipe Gallinago gallinago, Eurasian Curlew Arquata numenius and Common Redshank Tringa totanus). Although results for Curlew differed from the other species, in general field occupancy was positively influenced by conservation delivery mechanisms, with the highest occupancy and breeding densities on land where site protection was combined with wader‐specific AES options. Field occupancy varied between different types of AES, with higher occupancy associated with higher‐level options in fields, particularly those on nature reserves. Outside nature reserves, the history of AES management did not influence wader populations, but within nature reserves and on fields that gained AES management between 2002 and 2009–2010, populations of Curlew and Snipe were more likely to have persisted and population change in Snipe and Lapwing was more positive. We conclude that the conservation of breeding waders will be most effective when site protection and AES management are combined on the same land. Using limited AES money to support management for breeding waders on, around and between the existing network of protected sites will protect remaining populations while presenting opportunities for population expansion in future.
The recent description of the human genome and the subsequent annotation of putative novel genes has ushered in a new era in biology. One of the revelations of the human genome project was the ...remarkably consistent prediction that the genome harbors around 30,000 genes. This observation was based on independent analyses done by a public genome consortium (29,691 transcripts, Ensembl v0.8), by work done at Celera Genomics (39,114 transcripts), and by Green and colleagues using expressed sequence tag (EST) clustering incorporating quality scores (35,000 genes). This conclusion was surprising for two reasons. First, less complex organisms like Arabidopsis (25,000) and C. elegans (19,000) have approximately the same number of genes (C. elegans Sequencing Consortium, 1998; Arabidopsis Genome Initiative, 2000). Second, earlier estimates of gene number based on EST clustering and detailed chromosomal analysis were much higher, ranging from 45,000 to 140,000. While the Celera and Ensembl annotation efforts predicted approximately the same number of genes, a direct comparison of the predicted transcript sets has not been made. If the predictions are accurate and complete, then one would expect them to be largely overlapping. To address this point, we compared the predicted transcript sequences from the two genome efforts with each other and with a well-curated set of 11,015 reference transcripts from Refseq using BLAST. Given the difficulty of precisely predicting genes, we chose a permissive clustering method that requires only a short (>100 bp) region with at least 98% identity to combine transcripts into a single cluster. Using this method, transcripts that share only a single average size exon cluster together.
Capsule Bird and seed abundances decreased in both standard and enhanced Agri-Environment Scheme seed mixtures (plots of seed-bearing crops) between November and February. Aims We analysed effects of ...Agri-Environment seed mixture type (‘standard’ or ‘enhanced’), plot age and non-target species on seed and bird abundance. Methods Surveys were conducted in November/December and January/February on 36 standard and 19 enhanced seed mixtures to test effect of plot type and age on abundance of buntings, finches and seeds. Results Bunting and finch densities decreased between January/February and November/December. Seed decreased by approximately 70% between surveys, plot type did not affect depletion. Second-year plots contained nearly 90% less seed, and non-significantly lower bunting and finch densities. Bunting densities were positively related to cereal seed abundance, and finch densities to non-cereal seed; these relationships did not differ between plot types. There was no evidence that non-target species affected use of seed mixtures by target species. Conclusion There was no evidence that plot type affected seed or bird abundances. Increased quality and uptake of Agri-Environment Scheme seed-rich habitats (seed mixtures and over-winter stubbles, possibly alongside well-implemented supplementary feeding) is needed to provide late-winter seed, especially cereals for species of conservation concern.
Conserving farmland birds is a key objective for agri-environment schemes (AES) across Europe, with a number of management options aimed at providing invertebrate food and nesting habitats. We ...analysed territory settlement by two widespread but declining farmland buntings with contrasting nesting requirements: the Yellowhammer Emberiza citrinella, a boundary-nesting species, and the Corn Bunting Emberiza calandra, a ground-nesting species. The study was conducted on farms participating in the English Higher Level Stewardship scheme to test whether territory settlement is influenced by the provision of key arable AES options. Both species settled preferentially in localities containing sown arable field margins, while Corn Bunting also settled in localities containing nectar flower mixtures. These preferences are likely to reflect foraging rather than nesting habitat requirements. Yellowhammer selected territories containing hedgerows under AES management, which are nesting rather than foraging habitat but may also provide food. Uptake by land owners of several AES options likely to provide limiting resources for farmland birds was very low, and because uptake at the landscape scale is also low, wider-scale population level benefits are likely to be constrained. However, this is one of few studies demonstrating selection of widely applied arable AES options by breeding farmland birds.
Capsule Bunting densities decreased in winter wheat stubbles between November/December and January/February, but not in spring barley stubbles. Aims We investigated bird use and vegetation in ...relation to Agri-Environment Scheme over-winter stubble type and preceding crop. Methods We surveyed 15–17 fields each of: ‘standard’ Agri-Environment Scheme stubble on Entry Level Stewardship farms (EF6); ‘standard’ Agri-Environment Scheme stubble on Higher Level Stewardship farms (HF6); stubble preceded by low-input cereal (HF15); extended over-winter stubble (EF22) and non-Agri-Environment Scheme stubble in November/December 2011 and January/February 2012. Stubbles were preceded by spring barley or winter wheat crops. Results Previous cropping and time of year were the main factors influencing bird densities: bunting densities declined in winter wheat stubbles between surveys, but not in spring barley stubbles. Conclusion The main factor limiting the ability of over-winter stubbles to reverse national population trends of farmland birds is likely to be scale of provision. However, this study suggests that selecting spring barley crops to leave as over-winter stubbles may benefit granivorous farmland birds.
1. Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives ...from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2. During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3. The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4. The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5. Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible.
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