Recombination and linkage disequilibrium in Arabidopsis thaliana

Linkage disequilibrium (LD) is a major aspect of the organization of genetic variation in natural populations. Here we describe the genome-wide pattern of LD in a sample of 19 Arabidopsis thaliana accessions using 341,602 non-singleton SNPs. LD decays within 10 kb on average, considerably faster than previously estimated. Tag SNP selection algorithms and 'hide-the-SNP' simulations suggest that genome-wide association mapping will require only 40%-50% of the observed SNPs, a reduction similar to estimates in a sample of African Americans. An Affymetrix genotyping array containing 250,000 SNPs has been designed based on these results; we demonstrate that it should have more than adequate coverage for genome-wide association mapping. The extent of LD is highly variable, and we find clear evidence of recombination hotspots, which seem to occur preferentially in intergenic regions. LD also reflects the action of selection, and it is more extensive between nonsynonymous polymorphisms than between synonymous polymorphisms.     

A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.     

Pharmacodynamic profile of CQP 201-403, a novel 8α-amino-ergoline

Summary The profile of action in animals of CQP 201-403, a novel 8-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and to be more potent than bromocriptine (Parlodel^®).In memory of Dr Annemarie Closse, who died 14 June 1987.     

A new semisynthetic ergot peptide alkaloid: DCN 203-922

Summary We report the synthesis, stereochemistry and preliminary pharmacological evaluation of DCN 203-922, a novel ergot alkaloid of the cyclol type, which contains in its peptide moiety the uncommon amino acid L-allo-isoleucine.Part of this paper was reported by this author at the Herbstversammlung der Schweizerischen Chemischen Gesellschaft, Bern, in October 1986.     

The significance of nitrification for oceanic new production

The flux of organic material sinking to depth is a major control on the inventory of carbon in the ocean. To first order, the oceanic system is at equilibrium such that what goes down must come up. Because the export flux is difficult to measure directly, it is routinely estimated indirectly by quantifying the amount of phytoplankton growth, or primary production, fuelled by the upward flux of nitrate. To do so it is necessary to take into account other sources of biologically available nitrogen. However, the generation of nitrate by nitrification in surface waters has only recently received attention. Here we perform the first synthesis of open-ocean measurements of the specific rate of surface nitrification and use these to configure a global biogeochemical model to quantify the global role of nitrification. We show that for much of the world ocean a substantial fraction of the nitrate taken up is generated through recent nitrification near the surface. At the global scale, nitrification accounts for about half of the nitrate consumed by growing phytoplankton. A consequence is that many previous attempts to quantify marine carbon export, particularly those based on inappropriate use of the f-ratio (a measure of the efficiency of the 'biological pump'), are significant overestimates.     

An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

A new combination in Penstemon (Scrophulariaceae)

Field and herbarium studies of Penstemon cyananthus Hook. ssp. longiflorus Pennell suggest that this taxon be elevated to species rank.       

Suppression of in vitro haematopoiesis following human immunodeficiency virus infection

Viral infections are frequently associated with haematological disorders. Abnormalities including leukopenia, anaemia and thrombocytopenia are commonly observed in patients with the acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The underlying cause of these haematological abnormalities is poorly understood. We report here that bone marrow progenitors isolated from AIDS or ARC patients are responsive to recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) and recombinant erythropoietin. Antibodies present in the serum of patients infected with the human immunodeficiency virus (HIV), however, could suppress the growth of these progenitors, but not the growth of progenitors from HIV seronegative controls. A component of this immune-mediated suppression appears to be antibodies directed towards the envelope glycoprotein (gp120) of HIV.     

The PHYTOCHROME C photoreceptor gene mediates natural variation in flowering and growth responses of Arabidopsis thaliana

Light has an important role in modulating seedling growth and flowering time. We show that allelic variation at the PHYTOCHROME C (PHYC) photoreceptor locus affects both traits in natural populations of A. thaliana. Two functionally distinct PHYC haplotype groups are distributed in a latitudinal cline dependent on FRIGIDA, a locus that together with FLOWERING LOCUS C explains a large portion of the variation in A. thaliana flowering time. In a genome-wide scan for association of 65 loci with latitude, there was an excess of significant P values, indicative of population structure. Nevertheless, PHYC was the most strongly associated locus across 163 strains, suggesting that PHYC alleles are under diversifying selection in A. thaliana. Our work, together with previous findings, suggests that photoreceptor genes are major agents of natural variation in plant flowering and growth response.