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

Austenite nucleation and growth observed on the level of individual grains by three-dimensional X-ray diffraction microscopy

Austenite nucleation and growth is studied during continuous heating using three-dimensional X-ray diffraction (3-D XRD) microscopy at the European Synchrotron Radiation Facility (ESRF) (Grenoble, France). Unique in-situ observations of austenite nucleation and growth kinetics were made for two commercial medium-carbon low-alloy steels (0.21 and 0.35 wt pct carbon with an initial microstructure of ferrite and pearlite). The measured austenite volume fraction as a function of temperature shows a two-step behavior for both steel grades: it starts with a rather fast pearlite-to-austenite transformation, which is followed by a more gradual ferrite-to-austenite transformation. The austenite nucleus density exhibits similar behavior, with a sharp increase during the first stage of the transformation and a more gradual increase in the nucleus density in the second stage for the 0.21 wt pct carbon alloy. For the 0.35 wt pct carbon alloy, no new nuclei form during the second stage. Three different types of growth of austenite grains in the ferrite/pearlite matrix were observed. The combination of detailed separate observations of both nucleation and growth provides unique quantitative information on the phase transformation kinetics during heating, i.e., austenite formation from ferrite and pearlite.Materials Science and EngineeringMechanical, Maritime and Materials Engineerin