Novel gene function revealed by mouse mutagenesis screens for models of age-related disease

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Does Job Testing Harm Minority Workers? Evidence from Retail Establishments

Because minorities typically fare poorly on standardized tests, job testing is thought to pose an equality-efficiency trade-off: testing improves selection but reduces minority hiring. We develop a conceptual framework to assess when this trade-off is likely to apply and evaluate the evidence for such a trade-off using hiring and productivity data from a national retail firm whose 1,363 stores switched from informal to test-based worker screening over the course of one year. We document that testing yielded more productive hires at this firm-raising mean and median tenure by 10% or more. Consistent with prior research, minorities performed worse on the test. Yet, testing had no measurable impact on minority hiring, and productivity gains were uniformly large among minority and nonminority hires. These results suggest that job testing raised the precision of screening without introducing additional negative information about minority applicants, most plausibly because both the job test and the informal screen that preceded it were unbiased. (c) 2008 by the President and Fellows of Harvard College and the Massachusetts Institute of Technology..

L’animation comme industrie culturelle ? Concevoir et produire le dessin animé

L’animation, entendue ici dans toute la diversité de ses formats (longs et courts métrages de fiction, documentaires, publicités, etc.) et de ses techniques (celluloïd, images de synthèse, stop-motion, etc.), a longtemps été une niche scientifique, surtout en comparaison de l’intérêt exprimé pour d’autres médias ou industries culturelles. Certes, l’état de l’art s’est considérablement étoffé avec l’affirmation des « animation studies » dans le contexte anglo-saxon (Crafton, 1982 ; Pilling, 1997 ; Lamarre, 2008 ; Wells, 2012). De simple dénomination employée pour désigner certaines formations, départements d’universités ou encore cours au sein des écoles d’animation, l’expression est aujourd’hui devenue un label commode pour rassembler toutes les discussions et analyses engagées par des universitaires (et/ou certains praticiens) autour de l’animation… En savoir