Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. 1,2 Here we describe methods for large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short term culture. Analysis of 86,158 exonic SNPs that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.
This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library “MaStar”). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).
We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10 −7 to P = 4 × 10 −14 , with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.The malaria parasite Plasmodium falciparum kills on the order of a million African children each year 1 , and this is a small fraction of the number of infected individuals in the population [1][2][3] . In communities where everyone is repeatedly infected with P. falciparum, host genetic factors account for ~25% of the risk of severe malaria, that is, life-threatening forms of the disease 3 . The strongest known determinant of risk, hemoglobin S (HbS), accounts for 2% of the total variation, implying that only a small fraction of genetic resistance factors have so far been discovered 3 . Identifying the genetic basis of protective immunity against severe malaria may provide important insights for vaccine development.Here we examine the possibility of approaching this problem by genome-wide association (GWA) analysis. There are many unsolved methodological questions about how to conduct an effective GWA study in Africa 4 . High levels of ethnic diversity may result in false-positive associations owing to population structure. Variations in haplotype structure between different ethnic groups may reduce power to detect GWA signals, particularly when data are amalgamated across multiple study sites. Low LD implies the need for denser genotyping arrays than are currently available: a crude estimate is that an African GWA study with 1.5 million SNPs would have approximately the same statistical power as a European study with Jallow et al.Page 2Nat Genet. Author manuscript; available in PMC 2010 September 21. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 0.6 million SNPs5, but this is based on HapMap data from a single ethnic group and a larger number of SNPs may be needed to achieve adequate power across different ethnic groups.We carried out an initial GWA study in Gambian children that explores these methodological questions. Genotyping of ~500,000 SNPs was conducted on 1,060 cases of severe malaria and 1...
We present the first direct and unbiased measurement of the evolution of the dust mass function of galaxies over the past 5 billion years of cosmic history using data from the Science Demonstration Phase of the Herschel‐Astrophysical Terahertz Large Area Survey (Herschel‐ATLAS). The sample consists of galaxies selected at 250 m which have reliable counterparts from the Sloan Digital Sky Survey (SDSS) at z < 0.5, and contains 1867 sources. Dust masses are calculated using both a single‐temperature grey‐body model for the spectral energy distribution and also a model with multiple temperature components. The dust temperature for either model shows no trend with redshift. Splitting the sample into bins of redshift reveals a strong evolution in the dust properties of the most massive galaxies. At z= 0.4–0.5, massive galaxies had dust masses about five times larger than in the local Universe. At the same time, the dust‐to‐stellar mass ratio was about three to four times larger, and the optical depth derived from fitting the UV‐sub‐mm data with an energy balance model was also higher. This increase in the dust content of massive galaxies at high redshift is difficult to explain using standard dust evolution models and requires a rapid gas consumption time‐scale together with either a more top‐heavy initial mass function (IMF), efficient mantle growth, less dust destruction or combinations of all three. This evolution in dust mass is likely to be associated with a change in overall interstellar medium mass, and points to an enhanced supply of fuel for star formation at earlier cosmic epochs.
The sustainability of malaria control in Africa is threatened by the rise of insecticide resistance in Anopheles mosquitoes that transmit the disease1. To gain a deeper understanding of how mosquito populations are evolving, we sequenced the genomes of 765 specimens of Anopheles gambiae and Anopheles coluzzii sampled from 15 locations across Africa, identifying over 50 million single nucleotide polymorphisms within the accessible genome. These data revealed complex population structure and patterns of gene flow, with evidence of ancient expansions, recent bottlenecks, and local variation in effective population size. Strong signals of recent selection were observed in insecticide resistance genes, with multiple sweeps spreading over large geographical distances and between species. The design of novel tools for mosquito control using gene drive will need to take account of high levels of genetic diversity in natural mosquito populations.
We present the evolution in the number density and stellar mass functions of photometrically selected post-starburst galaxies in the UKIDSS Deep Survey (UDS), with redshifts of 0.5 < z < 2 and stellar masses log(M/M ⊙ )> 10. We find that this transitionary species of galaxy is rare at all redshifts, contributing ∼5% of the total population at z ∼ 2, to <1% by z ∼ 0.5. By comparing the mass functions of quiescent galaxies to post-starburst galaxies at three cosmic epochs, we show that rapid quenching of star formation can account for 100% of quiescent galaxy formation, if the post-starburst spectral features are visible for ∼250 Myr. The flattening of the low mass end of the quiescent galaxy stellar mass function seen at z ∼ 1 can be entirely explained by the addition of rapidly quenched galaxies. Only if a significant fraction of post-starburst galaxies have features that are visible for longer than 250 Myr, or they acquire new gas and return to the star-forming sequence, can there be significant growth of the red sequence from a slower quenching route. The shape of the mass function of these transitory post-starburst galaxies resembles that of quiescent galaxies at z ∼ 2, with a preferred stellar mass of log(M/M ⊙ )∼ 10.6, but evolves steadily to resemble that of star-forming galaxies at z < 1. This leads us to propose a dual origin for post-starburst galaxies: (1) at z > ∼ 2 they are exclusively massive galaxies that have formed the bulk of their stars during a rapid assembly period, followed by complete quenching of further star formation; (2) at z < ∼ 1 they are caused by the rapid quenching of gas-rich star-forming galaxies, independent of stellar mass, possibly due to environment and/or gas-rich major mergers.
The malaria parasite Plasmodium falciparum invades human red blood cells via interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB. We find that a nearby association with severe malaria is explained by a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes, which encode a serologically distinct blood group antigen known as Dantu. This variant reduces the risk of severe malaria by 40% and has recently risen in frequency in parts of Kenya, yet it appears to be absent from west Africa. These findings link structural variation of red blood cell invasion receptors with natural resistance to severe malaria.
We use the energy-balance code MAGPHYS to determine stellar and dust masses, and dust corrected star-formation rates for over 200,000 GAMA galaxies, 170,000 G10-COSMOS galaxies and 200,000 3D-HST galaxies. Our values agree well with previously reported measurements and constitute a representative and homogeneous dataset spanning a broad range in stellar mass (10 8 -10 12 M ), dust mass (10 6 -10 9 M ), and star-formation rates (0.01-100M yr −1 ), and over a broad redshift range (0.0 < z < 5.0). We combine these data to measure the cosmic star-formation history (CSFH), the stellar-mass density (SMD), and the dust-mass density (DMD) over a 12 Gyr timeline. The data mostly agree with previous estimates, where they exist, and provide a quasi-homogeneous dataset using consistent mass and star-formation estimators with consistent underlying assumptions over the full time range. As a consequence our formal errors are significantly reduced when compared to the historic literature. Integrating our cosmic star-formation history we precisely reproduce the stellar-mass density with an ISM replenishment factor of 0.50 ± 0.07, consistent with our choice of Chabrier IMF plus some modest amount of stripped stellar mass. Exploring the cosmic dust density evolution, we find a gradual increase in dust density with lookback time. We build a simple phenomenological model from the CSFH to account for the dust mass evolution, and infer two key conclusions: (1) For every unit of stellar mass which is formed 0.0065-0.004 units of dust mass is also formed; (2) Over the history of the Universe approximately 90 to 95 per cent of all dust formed has been destroyed and/or ejected.
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