Loss-of-function genetic diseases and the concept of pharmaceutical targets-0

<p><b>Copyright information:</b></p><p>Taken from "Loss-of-function genetic diseases and the concept of pharmaceutical targets"</p><p>http://www.OJRD.com/content/2/1/30</p><p>Orphanet Journal of Rare Diseases 2007;2():30-30.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936415.</p><p></p>ls of biological information. Once treatments are available for a few diseases, taking advantage of the connections will facilitate the identification of treatments for other diseases

Loss-of-function genetic diseases and the concept of pharmaceutical targets-1

<p><b>Copyright information:</b></p><p>Taken from "Loss-of-function genetic diseases and the concept of pharmaceutical targets"</p><p>http://www.OJRD.com/content/2/1/30</p><p>Orphanet Journal of Rare Diseases 2007;2():30-30.</p><p>Published online 2 Jul 2007</p><p>PMCID:PMC1936415.</p><p></p>ls of biological information. Once treatments are available for a few diseases, taking advantage of the connections will facilitate the identification of treatments for other diseases

Genomic coverage of <i>Mos1</i>.

<p>Graphical representation of each <i>C. elegans</i> chromosome showing the regions of the genome that are potentially amenable to genome engineering using the publicly-available <i>Mos1</i> alleles; it is assumed that any point up to 1.5 kb away from a transposon-insertion site can be targeted. The bottom line is a magnified view of the boxed region on chromosome X.</p

Distribution of <i>Mos1</i> alleles.

<p>(A) Graph showing the relationship between chromosome length (as a percentage of the whole nuclear genome) and the proportion of <i>Mos1</i> alleles per chromosome reported in a previous study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030482#pone.0030482-Granger1" target="_blank">[5]</a>, and the 10,858 alleles obtained in the current project (black and red circles, respectively). The outliers, concerning chromosomes I and V, from the previous study are highlighted with lines. (B) Distribution of distances from one <i>Mos1</i> allele to the next, in a 5′ to 3′ direction along each chromosome. The graph shows the cumulative percentage of alleles that are separated by less than the indicated distance. (C) Concentration of <i>Mos1</i> alleles at the extreme right end of chromosome I (length 15,072,423 bp). The separation of the allele numbers indicates that almost all the alleles were generated independently, except in two cases (ttTi2276 and ttTi2284; ttTi13453 and ttTi13460), highlighted by an asterisk. This region was also preferentially targeted during the previous study as reflected by the presence of several cxTi alleles.</p

Finding <i>Mos1</i> alleles with MosLocator.

<p>(A) MosLocator (<a href="http://www.ciml.univ-mrs.fr/applications/MosLocator" target="_blank">www.ciml.univ-mrs.fr/applications/MosLocator</a>) finds <i>Mos1</i> alleles using gene sequence or transcript names. For large lists of genetic gene names, the gene sequence or transcript names can be obtained using WormMart, or here, using WormBase Converter (<a href="http://www.ciml.univ-mrs.fr/applications/WB_converter" target="_blank">www.ciml.univ-mrs.fr/applications/WB_converter</a>) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030482#pone.0030482-Engelmann1" target="_blank">[15]</a>. In the example shown, the 23 <i>ptr</i> genes were used as input. (B) Screen grabs were captured to illustrate the use of MosLocator. Left panel: a list of sequence names was entered, and the search parameters were defined. Upper right panel: a display of the output for this search. Clicking on a non-zero number displayed in either of the last two columns, for example the “2” associated with the gene T21H3.2 (<i>ptr-16</i>), generates the display shown in the inset. This is a list of the 2 <i>Mos1</i> mutant alleles that are found within the gene T21H3.2. Each allele name is hyperlinked to Wormbase. (C) A partial view of the Variation report for the <i>Mos1</i> allele <i>ttTi21065</i> found on chromosome V at Wormbase (version WS225). (D) The genomic environment of the <i>ttTi21065</i> allele is displayed. The figure is a screen-grab from Wormbase.</p

Genome-wide distribution of <i>Mos1</i> mutant alleles.

<p>Chr: chromosome.</p

Summary of <i>Mos1</i> mutant production and characterization.

<p>Summary of <i>Mos1</i> mutant production and characterization.</p