Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called ‘HapMap 3’, includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of ≤5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

We present full-sky microwave maps in five frequency bands (23-94 GHz) from the Wilkinson Microwave Anisotropy Probe (WMAP) first-year sky survey. Calibration errors are less than 0.5%, and the low systematic error level is well specified. The cosmic microwave background (CMB) is separated from the foregrounds using multifrequency data. The sky maps are consistent with the 7 FWHM Cosmic Background Explorer (COBE) maps. We report more precise, but consistent, dipole and quadrupole values. The CMB anisotropy obeys Gaussian statistics with À58 < f NL < 134 (95% confidence level [CL]). The 2 ' 900 anisotropy power spectrum is cosmic-variance-limited for ' < 354, with a signal-to-noise ratio greater than 1 per mode to ' ¼ 658. The temperature-polarization cross-power spectrum reveals both acoustic features and a largeangle correlation from reionization. The optical depth of reionization is ¼ 0:17 AE 0:04, which implies a reionization epoch of t r ¼ 180 þ220 À80 Myr (95% CL) after the big bang at a redshift of z r ¼ 20 þ10 À9 (95% CL) for a range of ionization scenarios. This early reionization is incompatible with the presence of a significant warm dark matter density.A best-fit cosmological model to the CMB and other measures of large-scale structure works remarkably well with only a few parameters. The age of the best-fit universe is t 0 ¼ 13:7 AE 0:2 Gyr. Decoupling was t dec ¼ 379 þ8 À7 kyr after the big bang at a redshift of z dec ¼ 1089 AE 1. The thickness of the decoupling surface was Dz dec ¼ 195 AE 2. The matter density of the universe is m h 2 ¼ 0:135 þ0:008 À0:009 , the baryon density is b h 2 ¼ 0:0224 AE 0:0009, and the total mass-energy of the universe is tot ¼ 1:02 AE 0:02. It appears that there may be progressively less fluctuation power on smaller scales, from WMAP to fine-scale CMB measurements to galaxies and finally to the Ly forest. This may be accounted for with a running spectral index of scalar fluctuations, fitted as n s ¼ 0:93 AE 0:03 at wavenumber k 0 ¼ 0:05 Mpc À1 (' eff % 700), with a slope of dn s =d ln k ¼ À0:031 þ0:016 À0:018 in the best-fit model. (For WMAP data alone, n s ¼ 0:99 AE 0:04.) This flat universe model is composed of 4.4% baryons, 22% dark matter, and 73% dark energy. The dark energy equation of state is limited to w < À0:78 (95% CL). Inflation theory is supported with n s % 1, tot % 1, Gaussian random phases of the CMB anisotropy, and superhorizon fluctuations implied by the temperature-polarization anticorrelations at decoupling. An admixture of isocurvature modes does not improve the fit. The tensorto-scalar ratio is rðk 0 ¼ 0:002 Mpc À1 Þ < 0:90 (95% CL). The lack of CMB fluctuation power on the largest angular scales reported by COBE and confirmed by WMAP is intriguing. WMAP continues to operate, so results will improve.

Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a power-law distribution of the mutant allele frequencies reported by next-generation sequencing of tumor bulk samples. We find that the neutral power-law fits with high precision 323 of 904 cancers from 14 types, selected from different cohorts. In malignancies identified as neutral, all clonal selection occurred prior to the onset of cancer growth and not in later-arising subclones, resulting in numerous passenger mutations that are responsible for intra-tumor heterogeneity. Reanalyzing cancer sequencing data within the neutral framework allowed the measurement, in each patient, of both the in vivo mutation rate and the order and timing of mutations. This result provides a new way to interpret existing cancer genomic data and to discriminate between functional and non-functional intra-tumor heterogeneity.

The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems, as established by test beam measurements and simulation studies, is described.