X-linked inheritance of Fanconi anemia complementation group B

Fanconi anemia is an autosomal recessive syndrome characterized by diverse clinical symptoms, hypersensitivity to DNA crosslinking agents, chromosomal instability and susceptibility to cancer. Fanconi anemia has at least 11 complementation groups (A, B, C, D1, D2, E, F, G, I, J, L); the genes mutated in 8 of these have been identified. The gene BRCA2 was suggested to underlie complementation group B, but the evidence is inconclusive. Here we show that the protein defective in individuals with Fanconi anemia belonging to complementation group B is an essential component of the nuclear protein 'core complex' responsible for monoubiquitination of FANCD2, a key event in the DNA-damage response pathway associated with Fanconi anemia and BRCA. Unexpectedly, the gene encoding this protein, FANCB, is localized at Xp22.31 and subject to X-chromosome inactivation. X-linked inheritance has important consequences for genetic counseling of families with Fanconi anemia belonging to complementation group B. Its presence as a single active copy and essentiality for a functional Fanconi anemia-BRCA pathway make FANCB a potentially vulnerable component of the cellular machinery that maintains genomic integrity.     

Perennial water ice identified in the south polar cap of Mars

The inventory of water and carbon dioxide reservoirs on Mars are important clues for understanding the geological, climatic and potentially exobiological evolution of the planet. From the early mapping observation of the permanent ice caps on the martian poles, the northern cap was believed to be mainly composed of water ice, whereas the southern cap was thought to be constituted of carbon dioxide ice. However, recent missions (NASA missions Mars Global Surveyor and Odyssey) have revealed surface structures, altimetry profiles, underlying buried hydrogen, and temperatures of the south polar regions that are thermodynamically consistent with a mixture of surface water ice and carbon dioxide. Here we present the first direct identification and mapping of both carbon dioxide and water ice in the martian high southern latitudes, at a resolution of 2 km, during the local summer, when the extent of the polar ice is at its minimum. We observe that this south polar cap contains perennial water ice in extended areas: as a small admixture to carbon dioxide in the bright regions; associated with dust, without carbon dioxide, at the edges of this bright cap; and, unexpectedly, in large areas tens of kilometres away from the bright cap.     

Developmental control of heat shock and chaperone gene expression Hsp70 genes and heat shock factors during preimplantation phase of mouse development

Heat shock genes are found in all organisms, and synthesis of heat shock proteins is induced by various stressors in nearly all the cells forming these organisms. However, a particular situation is noticed for hsp70 genes in mouse embryos at the beginning of their development. First, spontaneous expression of hsp70 is observed at the onset of zygotic genome activity. Second, inducible expression is delayed until morula or early blastocyst stages. A better understanding of both these points depends on a more careful analysis of hsp70 expression in relation to their major regulators, the heat shock factors. In this review, we will see how the development of the preimplanta tion embryo highlights the complexity of heat shock gene regulation involving trans-cis interactions and the cellular and nuclear environment.     

European Science Foundation: Report on the Scientific Networks 1985–1990 Excerpts from the ESF Communications

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European Science Foundation: Report on the Scientific Networks 1985–1990Excerpts from the ESF Communications     

Varignon ou la théorie du mouvement des projectiles ‘comprise en une Proposition générale

Cet article a pour objet de montrer la nouveauté du traitement varignonien du mouvement des projectiles dans les milieux résistants par rapport au traitement de ce problème présenté entre autres par Newton dans les Principia. Aussi, après avoir analysé cursivement différentes Propositions du Livre II des Principia, nous étudierons plus spécialement, dans les Mémoires présentés par Varignon à l'Académie Royale des Sciences entre 1707 et 1711, la mise en place de l'expression d'une ‘Proposition générale’. Nous montrerons ensuite sur quelques cas particuliers en quel sens on peut dire que l'étude du mouvement des projectiles dans les milieux résistants se réduit alors, pour l'essentiel, à de simples questions d'intégration et de différentiation.     

A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.     

Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease

Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ～20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.