Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Recent advances in molecular genetic linkage maps of cultivated peanut

The competitiveness of peanuts in domestic and global markets has been threatened by losses in productivity and quality that are attributed to diseases, pests, environmental stresses and allergy or food safety issues. Narrow genetic diversity and a deficiency of polymorphic DNA markers severely hindered construction of dense genetic maps and quantitative trait loci (QTL) mapping in order to deploy linked markers in marker-assisted peanut improvement. The U.S. Peanut Genome Initiative (PGI) was launched in 2004, and expanded to a global effort in 2006 to address these issues through coordination of international efforts in genome research beginning with molecular marker development and improvement of map resolution and coverage. Ultimately, a peanut genome sequencing project was launched in 2012 by the Peanut Genome Consortium (PGC). We reviewed the progress for accelerated development of peanut genomic resources in peanut, such as generation of expressed sequenced tags (ESTs) (252,832 ESTs as December 2012 in the public NCBI EST database), development of molecular markers (over 15,518 SSRs), and construction of peanut genetic linkage maps, in particular for cultivated peanut. Several consensus genetic maps have been constructed, and there are examples of recent international efforts to develop high density maps. An international reference consensus genetic map was developed recently with 897 marker loci based on 11 published mapping populations. Furthermore, a high-density integrated consensus map of cultivated peanut and wild diploid relatives also has been developed, which was enriched further with 3693 marker loci on a single map by adding information from five new genetic mapping populations to the published reference consensus map

Mise au point: cancer du sein et grossesse. Revue de la littérature.

The pregnancy-associated breast cancer seems to have become increasingly common with a high frequency of advanced breast cancer with axillary node metastases and so associated with poor prognosis.English AbstractJournal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Shock tunnel and numerical studies of a large inlet-fuelled inward turning axisymmetric scramjet

A large axisymmetric inward turning inlet-fuelled scramjet flowpath has been tested at flight Mach 8 enthalpy in the High Enthalpy Shock Tunnel Göttingen (HEG) of the German Aerospace Center (Martinez Schramm et al (2012), as part of the international SCRAMSPACE program. Experiments have been conducted that explore the fuel-off flow structure and the effects of fuel injection, mixing and combustion over a range of Reynolds numbers (1.3×106 to 3.9×106 m-1) and fuelling rates (φ = 0.0 to 0.98). The test flows have been reconstructed with RANS CFD, employing the SST turbulence model and the Jachimowski (1992) hydrogen/air combustion model. The experimental results indicate a highly axisymmetric fuel-off flow, mild three-dimensional effects due to fuel injection, and a variety of effects of combustion heat release. CFD modeling produces excellent agreement with the experimental data, except at high pressure and high fuelling rates

The Trouble with Diffusion

The phenomenological formalism, which yields Fick's Laws for diffusion in single phase multicomponent systems, is widely accepted as the basis for the mathematical description of diffusion. This paper focuses on problems associated with this formalism. This mode of description of the process is cumbersome, defining as it does matrices of interdiffusion coefficients (the central material properties) that require a large experimental investment for their evaluation in three component systems, and, indeed cannot be evaluated for systems with more than three components. It is also argued that the physical meaning of the numerical values of these properties with respect to the atom motions in the system remains unknown. The attempt to understand the physical content of the diffusion coefficients in the phenomenological formalism has been the central fundamental problem in the theory of diffusion in crystalline alloys. The observation by Kirkendall that the crystal lattice moves during diffusion led Darken to develop the concept of intrinsic diffusion, i.e., atom motion relative to the crystal lattice. Darken and his successors sought to relate the diffusion coefficients computed for intrinsic fluxes to those obtained from the motion of radioactive tracers in chemically homogeneous samples which directly report the jump frequencies of the atoms as a function of composition and temperature. This theoretical connection between tracer, intrinsic and interdiffusion behavior would provide the basis for understanding the physical content of interdiffusion coefficients. Definitive tests of the resulting theoretical connection have been carried out for a number of binary systems for which all three kinds of observations are available. In a number of systems predictions of intrinsic coefficients from tracer data do not agree with measured values although predictions of interdiffusion coefficients appear to give reasonable agreement. Thus, the complete connection has not been made, even for binary systems. The theory has never been tested in multicomponent systems. An alternative path to understanding diffusion behavior in multicomponent systems is presented which is based upon a kinetically derived version of the flux equations. While this approach has problems of its own, it has the potential for providing a new range of insights into the process, and for devising simple models for predicting composition evolution in multicomponent systems

A map of human genome variation from population-scale sequencing

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research