Low-mass pre--main-sequence stars in the Magellanic Clouds

[Abridged] The stellar Initial Mass Function (IMF) suggests that sub-solar stars form in very large numbers. Most attractive places for catching low-mass star formation in the act are young stellar clusters and associations, still (half-)embedded in star-forming regions. The low-mass stars in such regions are still in their pre--main-sequence (PMS) evolutionary phase. The peculiar nature of these objects and the contamination of their samples by the evolved populations of the Galactic disk impose demanding observational techniques for the detection of complete numbers of PMS stars in the Milky Way. The Magellanic Clouds, the companion galaxies to our own, demonstrate an exceptional star formation activity. The low extinction and stellar field contamination in star-forming regions of these galaxies imply a more efficient detection of low-mass PMS stars than in the Milky Way, but their distance from us make the application of special detection techniques unfeasible. Nonetheless, imaging with the Hubble Space Telescope yield the discovery of solar and sub-solar PMS stars in the Magellanic Clouds from photometry alone. Unprecedented numbers of such objects are identified as the low-mass stellar content of their star-forming regions, changing completely our picture of young stellar systems outside the Milky Way, and extending the extragalactic stellar IMF below the persisting threshold of a few solar masses. This review presents the recent developments in the investigation of PMS stars in the Magellanic Clouds, with special focus on the limitations by single-epoch photometry that can only be circumvented by the detailed study of the observable behavior of these stars in the color-magnitude diagram. The achieved characterization of the low-mass PMS stars in the Magellanic Clouds allowed thus a more comprehensive understanding of the star formation process in our neighboring galaxies.Comment: Review paper, 26 pages (in LaTeX style for Springer journals), 4 figures. Accepted for publication in Space Science Review

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

Skewed X-inactivation is common in the general female population

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants