A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms

We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.     

Anaerobic benzene oxidation coupled to nitrate reduction in pure culture by two strains of Dechloromonas.

Benzene contamination is a significant problem. It is used in a wide range of manufacturing processes and is a primary component of petroleum-based fuels. Benzene is a hydrocarbon that is soluble, mobile, toxic and stable, especially in ground and surface waters. It is poorly biodegraded in the absence of oxygen. However, anaerobic benzene biodegradation has been documented under various conditions. Although benzene biomineralization has been demonstrated with nitrate, Fe(III), sulphate or CO2 as alternative electron acceptors, these studies were based on sediments or microbial enrichments. Until now there were no organisms in pure culture that degraded benzene anaerobically. Here we report two Dechloromonas strains, RCB and JJ, that can completely mineralize various mono-aromatic compounds including benzene to CO2 in the absence of O2 with nitrate as the electron acceptor. This is the first example, to our knowledge, of an organism of any type that can oxidize benzene anaerobically, and we demonstrate the potential applicability of these organisms to the treatment of contaminated environments.     

A conserved sequence at c-myc oncogene chromosomal translocation breakpoints in plasmacytomas

Many recent studies have shown that chromosomal translocation breakpoints frequently occur near cellular proto-oncogenes (reviewed in ref. 1). In both mouse plasmacytomas and Burkitt lymphomas, the c-myc oncogene becomes joined to an immunoglobulin heavy-chain gene in a head-to-head configuration. Within c-myc, the breaks frequently occur near the first exon-intron boundary, while within the immunoglobulin gene the breaks usually involve sequences directing heavy-chain switching. It has been assumed that the translocations represent abortive immunoglobulin switching events which have activated the c-myc gene for a role in tumour formation. However, sequence analysis of the c-myc gene does not reveal any apparent similarity to the immunoglobulin switch signals. With these results in mind, we have determined the precise breakpoints within c-myc for two plasmacytoma lines in order to search for any common features that may shed some light on the mechanism of chromosomal translocation. We report here that the tetranucleotide sequence GAGG occurs close to the breakpoint in five out of six translocations, and so may be a sequence recognized by either the enzymes that catalyse immunoglobulin heavy-chain switching, or some other DNA-cleaving activity.     

One or more bound planets per Milky Way star from microlensing observations

Most known extrasolar planets (exoplanets) have been discovered using the radial velocity or transit methods. Both are biased towards planets that are relatively close to their parent stars, and studies find that around 17-30% (refs 4, 5) of solar-like stars host a planet. Gravitational microlensing, on the other hand, probes planets that are further away from their stars. Recently, a population of planets that are unbound or very far from their stars was discovered by microlensing. These planets are at least as numerous as the stars in the Milky Way. Here we report a statistical analysis of microlensing data (gathered in 2002-07) that reveals the fraction of bound planets 0.5-10?AU (Sun-Earth distance) from their stars. We find that 17(+6)(-9)% of stars host Jupiter-mass planets (0.3-10?M(J), where M(J) = 318?M(⊕) and M(⊕) is Earth's mass). Cool Neptunes (10-30?M(⊕)) and super-Earths (5-10?M(⊕)) are even more common: their respective abundances per star are 52(+22)(-29)% and 62(+35)(-37)%. We conclude that stars are orbited by planets as a rule, rather than the exception.     

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.