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- 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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| 3. |
- Taha, Muhamed-Kheir, et al.
(författare)
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Defining the breakpoint for resistance to rifampicin in Neisseria meningitidis by rpoB sequencing
- 2009
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Clinical isolates of Neisseria meningitidis resistant to rifampicin are important to identify asthey lead to failure of chemoprophylaxis of meningococcal disease. However, theidentification of these isolates is hindered by the absence of a harmonized breakpoint despiteefforts of standardization. In the present study, a large number (n=352) of clinical N.meningitidis isolates from 12 mainly European countries and spanning over 25 years (1984 to2009) were examined. The collection comprised all clinical isolates with MIC 0.25 mg/lreceived by the national reference laboratories for meningococci in the participating countries(n=161). In addition, representative isolates displaying MIC of rifampicin <0.25 mg/l wereexamined (n=191). Phenotyping and genotyping of isolates were performed and a 660 bpDNA fragment of the rpoB gene was sequenced in all the included isolates. Sequencesdiffering by at least one nucleotide were defined as a unique rpoB allele (n=55). Geometricmeans of MIC were calculated for isolates displaying the same allele. All the clinical isolatesdisplaying MIC >1 mg/l of rifampicin possessed rpoB alleles with critical mutations (in total21 alleles), resulting in substitutions at the codon H552 and less frequently at nearby codons(S548 and S557). These alterations were absent in the alleles (n=34) found in all isolates withMIC 1 mg/l. Based on these findings, rifampicin susceptible isolates could be defined asthose with MIC 1 mg/l. A new web site was created based on the data from this work (http://neisseria.org/nm/typing/rpoB). The rifampicin resistant isolates belonged to diversegenetic lineages and provoked lower bacteremia levels in mice. This biological cost mayexplain the non-expansion of the rifampicin resistant isolates.
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