| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Lindgren, Cecilia M, et al.
(författare)
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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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| 3. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 4. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 5. |
- Liti, Gianni, et al.
(författare)
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Population genomics of domestic and wild yeasts.
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 458:7236, s. 337-41
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Tidskriftsartikel (refereegranskat)abstract
- Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of studies looking at ecological and geographic distributions, population structure and sexual versus asexual reproduction. Less well understood at the whole genome level are the evolutionary processes acting within populations and species that lead to adaptation to different environments, phenotypic differences and reproductive isolation. Here we present one- to fourfold or more coverage of the genome sequences of over seventy isolates of the baker's yeast S. cerevisiae and its closest relative, Saccharomyces paradoxus. We examine variation in gene content, single nucleotide polymorphisms, nucleotide insertions and deletions, copy numbers and transposable elements. We find that phenotypic variation broadly correlates with global genome-wide phylogenetic relationships. S. paradoxus populations are well delineated along geographic boundaries, whereas the variation among worldwide S. cerevisiae isolates shows less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.
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| 6. |
- Greenhalgh, Christopher J, et al.
(författare)
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SOCS2 negatively regulates growth hormone action in vitro and in vivo.
- 2005
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 115:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30-50% increase in mature body size. Here we show that the SOCS2-/- phenotype is dependent upon the presence of endogenous growth hormone (GH) and that treatment with exogenous GH induced excessive growth in mice lacking both endogenous GH and SOCS2. This was reflected in terms of overall body weight, body and bone lengths, and the weight of internal organs and tissues. A heightened response to GH was also measured by examining GH-responsive genes expressed in the liver after exogenous GH administration. To further understand the link between SOCS2 and the GH-signaling cascade, we investigated the nature of these interactions using structure/function and biochemical interaction studies. Analysis of the 3 structural motifs of the SOCS2 molecule revealed that each plays a crucial role in SOCS2 function, with the conserved SOCS-box motif being essential for all inhibitory function. SOCS2 was found to bind 2 phosphorylated tyrosines on the GH receptor, and mutational analysis of these amino acids showed that both were essential for SOCS2 function. Together, the data provide clear evidence that SOCS2 is a negative regulator of GH signaling.
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| 7. |
- Izumi, Hironari, et al.
(författare)
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Bacteria associated with ectomycorrhizas of slash pine (Pinus elliottii) in south-eastern Queensland, Australia
- 2008
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Ingår i: Fems Microbiology Letters. - : Oxford University Press (OUP). - 0378-1097 .- 1574-6968. ; 282:2, s. 196-204
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial communities associated with ectomycorrhizal and uncolonized roots of Pinus elliottii (slash pine) collected from a plantation in south-east Queensland, Australia, were investigated, using cultivation-dependent and -independent methods. Denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene PCR products obtained using a cultivation-independent approach revealed that bacterial communities associated with ectomycorrhizal root tips differed significantly from those associated with roots uncolonized by ectomycorrhizal fungi. DGGE analysis of cultivable bacterial communities revealed no significant difference between ectomycorrhizal and uncolonized roots. Neither analytical approach revealed significant differences between the bacterial communities associated with ectomycorrhizal roots colonized by a Suillus sp. or an Atheliaceae taxon. Cloned bacterial 16S rRNA genes revealed sequence types closely related with that of Burkholderia phenazinium, common in both ectomycorrhizal-colonized and -uncolonized roots, while sequence types most similar to the potentially phyopathogenic bacteria Burkholderia andropogonis and Pantoea ananatis were only detected in ectomycorrhizal roots. These results highlight the possibility of global movement of microorganisms, including putative pathogens, as a result of the introduction of exotic pine plantations.
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| 8. |
- Izumi, Hironari, et al.
(författare)
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Diversity and expression of nitrogenase genes (nifH) from ectomycorrhizas of Corsican pine (Pinus nigra).
- 2006
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Ingår i: Environmental microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 8:12, s. 2224-30
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Tidskriftsartikel (refereegranskat)abstract
- The diversity of bacterial nitrogenase genes (nifH) and their mRNA transcription in ectomycorrhizas of Corsican pine (Pinus nigra) were examined. DNA and RNA were extracted from surface-sterilized and non-sterilized Corsican pine roots colonized by the ectomycorrhizal (ECM) fungi, Suillus variegatus and Tomentellopsis submollis. DNA-derived nifH polymerase chain reaction (PCR) products were obtained from all samples, but only a few reverse transcription PCRs for nifH mRNA were successful, suggesting that nitrogenase genes were not always transcribed. Several different nifH sequences were detected and the bacteria actively transcribing nifH were different from those whose genes were detected through DNA-based PCR. Putative nitrogenase amino acid sequences revealed that more than half of the nifH products were derived from methylotrophic bacteria, such as Methylocella spp. The next most frequent sequence types were similar to those from Burkholderia.
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