Bertrand Jordan

Maladie de Crohn et GWAS, d’analyses en méta-analyses - Chroniques génomiques

Les études d’association génétique à grande échelle (genome-wide association studies , GWAS) se poursuivent de plus belle : il s’en est pratiqué aujourd’hui plus d’un millier et, à lire les sommaires de Nature Genetics, on pourrait être tenté de rebaptiser cette revue Nature GWAS... Compte tenu du nombre de travaux publiés, mais aussi d’une méthodologie maintenant bien établie et de critères statistiques précis et homogènes, il s’avère possible de combiner plusieurs études portant sur la même affection afin d’en accroître la puissance statistique et de mettre ainsi en évidence des locus qui ne pouvaient être identifiés de manière concluante dans les analyses originelles. Je vais commenter ici les enseignements d’une méta-analyse très récente portant sur la maladie de Crohn qui montre la puissance mais aussi les limites de cette approche. Rappelons tout d’abord que la maladie de Crohn est une affection inflammatoire chronique touchant différents segments du tube digestif, maladie grave entraînant toutes sortes de troubles, sans traitement autre que symptomatique et pouvant déboucher sur une chirurgie mutilante. Elle est relativement fréquente, avec une prévalence de deux à quatre pour mille, et présente une composante génétique importante : son héritabilité au sens strict a été évaluée à 50 % [1]. C’est donc, à l’évidence, une cible intéressante pour des études génétiques susceptibles d’éclairer son étiologie, d’améliorer le diagnostic et, à terme, de favoriser la mise au point de traitements efficaces. Les premiers travaux, « pré-GWAS », ont permis d’identifier de manière concluante le gène NOD21,

L’ADN comme mémoire informatique ?: Chroniques génomiques

The very high information density of DNA has prompted speculations on its use for information storage. The high costs of DNA synthesis and sequencing made this highly unpractical; however recent progress (notably array oligonucleotide synthesis) is changing the situation. A recent paper shows encoding and decoding of significant amounts of data (200 MB) with random access to individual files and faithful retrieval of content, at a cost that is still high but not extreme. Much progress remains to be achieved, but this use of DNA in now technically achievable and may eventually become practical.

Bases alternatives et organismes synthétiques: Chroniques Génomiques

Alternative bases that can fit into the DNA double helix have now been used in vivo to direct the synthesis of proteins incorporating unnatural amino acids. This bioengineering feat is significant at both the conceptual and the practical levels.

Espérance de vie et traces des cataclysmes - Chroniques génomiques

Life expectancy curves for several nations provide an astonishingly precise image of the major events that occurred during the last century, highlight similarities between France and Great Britain, and reflect the tremendous economic hardship associated with the end of the Soviet Union.

Modification ciblée du génome : une nouvelle approche prometteuse - Chroniques génomiques

A new approach, based on the use of peptide nucleic acid molecules to form triple helices and promote locus-specific recombination, demonstrates potential for in vivo gene correction at clinically significant levels and may provide a promising avenue for gene therapy.A new approach, based on the use of peptide nucleic acid molecules to form triple helices and promote locus-specific recombination, demonstrates potential for in vivo gene correction at clinically significant levels and may provide a promising avenue for gene therapy.

Variants rares et explosion démographique - Chroniques génomiques

The abundance of rare variants in human DNA is the consequence of tremendous recent expansion of our population. Careful measurement of neutral variants in a European population points to more recent and more rapid expansion than previously believed.

Les leçons inattendues d’Hiroshima - Chroniques génomiques

One of the initial motivations for the Genome project was to improve the detection of possible mutations in children of atomic bomb survivors. In fact it has proved very difficult to find any genetic effect in these descendants in spite of the strong irradiation suffered by their parents: this factual evidence is largely ignored in the current debates about the effects of radiation and the future of nuclear energy. Sequencing studies on this population would be very desirable.

Chroniques génomiques - Un chapeau pour mon repas ?

After clearing many hurdles, gene therapy is now reaching the commercialization stage and can be expected to make a modest but real contribution to treatment in the near future.

Les survivants d’Hiroshima/Nagasaki et leur descendance - Les enseignements d’une étude épidémiologique à long terme

After the atomic bombing of Hiroshima and Nagasaki, long-term epidemiological studies were undertaken on the irradiated survivors and their offspring, and are still underway. These thorough studies involving tens of thousands of persons and published in hundreds of papers have shown a moderate increase in cancer incidence for irradiated survivors, with limited impact on their life span (loss of one year at most). In studies on the offspring of these survivors, no statistically significant deleterious effect on malformation frequency, incidence of mutations or mortality from cancer and other diseases has been seen so far. These data are actually the basis for current radiation safety levels; they show that health risks from radiation are limited, but they are not applicable to complex situations such as nuclear power station accidents that involve diverse types of radiation as well as contamination by radioactive materials.

CRISPR sur embryons humains : une nouvelle étape - Chroniques génomiques

Viable human embryos carrying a disease mutation have now been corrected by CRISPR-Cas9 editing. Although the correction is not perfect, and the embryos have not been implanted, this brings us closer to human germline editing and to the associated ethical questions.