| 1. |
- 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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| 2. |
- Baker, Naomi L., et al.
(författare)
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Molecular consequences of dominant Bethlem myopathy collagen VI mutations
- 2007
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 62:4, s. 390-405
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of the fingers, wrists, and ankles. Although more than 20 different dominant mutations have been identified in Bethlem myopathy patients, the biosynthetic consequences of only a subset of these have been studied, and in many cases, the pathogenic mechanisms remain unknown. Methods: We have screened fourteen Bethlem myopathy patients for collagen VI mutations and performed detailed analyses of collagen VI biosynthesis and intracellular and extracellular assembly. Results: Collagen VI abnormalities were identified in eight patients. One patient produced around half the normal amount of alpha 1(VI) messenger RNA and reduced amounts of collagen VI protein. Two patients had a previously reported mutation causing skipping of COL6A1 exon 14, and three patients had novel mutations leading to in-frame deletions toward the N-terminal end of the triple-helical domain. These mutations have different and complex effects on collagen VI intracellular and extracellular assembly. Two patients had single amino acid substitutions in the A-domains of COL6A2 and COL6A3. Collagen VI intracellular and extracellular assembly was normal in one of these patients. Interpretation: The key to dissecting the pathogenic mechanisms of collagen VI mutations lies in detailed analysis of collagen VI biosynthesis and assembly. The majority of mutations result in secretion and deposition of structurally abnormal collagen VI. However, one A-domain mutation had no detectable effect on assembly, suggesting that it acts by compromising collagen VI interactions in the extracellular matrix of muscle.
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| 3. |
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| 4. |
- Field, Dawn, et al.
(författare)
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The minimum information about a genome sequence (MIGS) specification.
- 2008
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 26:5, s. 541-7
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Tidskriftsartikel (refereegranskat)abstract
- With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.
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| 5. |
- Jhavar, Sameer, et al.
(författare)
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Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer
- 2009
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Ingår i: BJU International. - 1464-4096. ; 103:9, s. 1256-1269
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To integrate the mapping of ERG alterations with the collection of expression microarray (EMA) data, as previous EMA analyses have failed to consider the genetic heterogeneity and complex patterns of ERG alteration frequently found in cancerous prostates. MATERIALS AND METHODS We determined genome-wide expression levels with GeneChip Human Exon 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 35 specimens of prostate cancer from 28 prostates. RESULTS The expression profiles showed clustering, in unsupervised hierarchical analyses, into two distinct prostate cancer categories, with one group strongly associated with indicators of poor clinical outcome. The two categories are not tightly linked to ERG status. By analysis of the data we identified a subgroup of cancers lacking ERG rearrangements that showed an outlier pattern of SPINK1 mRNA expression. There was a major distinction between ERG rearranged and non-rearranged cancers that involves the levels of expression of genes linked to exposure to beta-oestradiol, and to retinoic acid. CONCLUSIONS Expression profiling of prostate cancer samples containing single patterns of ERG alterations can provide novel insights into the mechanism of prostate cancer development, and support the view that factors other than ERG status are the major determinants of poor clinical outcome.
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