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Mendizabal, Isabel et al. ; The Romani, the largest European minority group with approximately 11 million people [1], constitute a mosaic of languages, religions, and lifestyles while sharing a distinct social heritage. Linguistic [2] and genetic [3-8] studies have located the Romani origins in the Indian subcontinent. However, a genome-wide perspective on Romani origins and population substructure, as well as a detailed reconstruction of their demographic history, has yet to be provided. Our analyses based on genome-wide data from 13 Romani groups collected across Europe suggest that the Romani diaspora constitutes a single initial founder population that originated in north/northwestern India ∿1.5 thousand years ago (kya). Our results further indicate that after a rapid migration with moderate gene flow from the Near or Middle East, the European spread of the Romani people was via the Balkans starting ∿0.9 kya. The strong population substructure and high levels of homozygosity we found in the European Romani are in line with genetic isolation as well as differential gene flow in time and space with non-Romani Europeans. Overall, our genome-wide study sheds new light on the origins and demographic history of European Romani. © 2012 Elsevier Ltd. ; I.M. was supported by a PhD grant by the Basque Government (Hezkuntza, Unibertsitate eta Ikerketa Saila, Eusko Jaurlaritza, BFI107.4). O.L., A.W., and M.K. were supported by the Erasmus MC University Medical Center Rotterdam. U.M.M. was supported by a PhD grant by Universitat Pompeu Fabra. M.G.N. was supported by a Vici grant of the Netherlands Organization of Scientific Research. L.G. was supported by an Invited Professor grant from CAPES/Brazil. A.M. was supported by the Estonian Government grant SF0180142s08. This study was supported in parts by Spanish Government MCINN grant CGL2010-14944/BOS to D.C., Czech Republic Ministry of Health grants CZ.2.16/3.1.00/24022 and 00064203 to M.M., Republic of Serbia Ministry of Education and Science grant ON173008 to D.R., Belgium University of Antwerp grant IWS BOFUA 2008/23064 to A.J., and Portuguese Foundation for Science and Technology (FCT) project grant PTDC/ANT/70413/2006 to L.G. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Education and Science and is partially supported by the FCT. ; Peer Reviewed

This article is published with open access at Springerlink.com.-- This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. ; African Pygmies are hunter-gatherer populations from the equatorial rainforest that present the lowest height averages among humans. The biological basis and the putative adaptive role of the short stature of Pygmy populations has been one of the most intriguing topics for human biologists in the last century, which still remains elusive. Worldwide convergent evolution of the Pygmy size suggests the presence of strong selective pressures on the phenotype. We developed a novel approach to survey the genetic architecture of phenotypes and applied it to study the genomic covariation between allele frequencies and height measurements among Pygmy and non-Pygmy populations. Among the regions that were most associated with the phenotype, we identified a significant excess of genes with pivotal roles in bone homeostasis, such as PPPT3B and the height associated SUPT3H-RUNX2. We hypothesize that skeletal remodeling could be a key biological process underlying the Pygmy phenotype. In addition, we showed that these regions have most likely evolved under positive selection. These results constitute the first genetic hint of adaptive evolution in the African Pygmy phenotype, which is consistent with the independent emergence of the Pygmy height in other continents with similar environments. © 2012 Springer-Verlag. ; IM was supported by a PhD fellowship by the Basque Government (Hezkuntza, Unibertsitate eta Ikerketa Saila, Eusko Jaurlaritza, BFI107.4); UMM was supported by a PhD fellowship from Universitat Pompeu Fabra. This work was partially supported by the Spanish Ministry of Science and Innovation (Grant CGL2010-14944/BOS), Direcció General de Recerca, Generalitat de Catalunya (2009SGR-1101) and by the Netherlands Forensic Institute (NFI), the Erasmus MC University Medical Center Rotterdam, and the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) within the framework of the Forensic Genomics Consortium Netherlands (FGCN). ; Peer Reviewed

Olalde, Iñigo et al.-- This work is licensed under a Creative Commons Attribution 3.0 Unported License. ; A pyrographically decorated gourd, dated to the French Revolution period, has been alleged to contain a handkerchief dipped into the blood of the French king Louis XVI (1754-1793) after his beheading but recent analyses of living males from two Bourbon branches cast doubts on its authenticity. We sequenced the complete genome of the DNA contained in the gourd at low coverage (∼2.5×) with coding sequences enriched at a higher ∼7.3× coverage. We found that the ancestry of the gourd's genome does not seem compatible with Louis XVI's known ancestry. From a functional perspective, we did not find an excess of alleles contributing to height despite being described as the tallest person in Court. In addition, the eye colour prediction supported brown eyes, while Louis XVI had blue eyes. This is the first draft genome generated from a person who lived in a recent historical period; however, our results suggest that this sample may not correspond to the alleged king. ; This work is supported by FEDER and Spanish Government grants BFU2012-38236 and the Spanish Multiple Sclerosis Netowrk (REEM) of the Instituto de Salud Carlos III (RD12/0032/0011) to A.N., BFU2011-28549 and ERC Starting Grant (260372) to T.M.-B. and BFU2012-34157 to C.L.-F. and S.C., and a predoctoral fellowship from the Basque Government (DEUI) to I.O. ; Peer Reviewed

The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008–2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0. ; EF acknowledges support from the advanced ERC grant (ERC-2011-AdG 295642-FEP) on the Foundation of Economic Preferences. MK, BM, and KRM were supported by the German National Science Foundation (DFG) under the grants MU 987/6-1 and RA 1894/1-1. TD and DS were supported by the German National Science Foundation (DFG) under the grants DI 1723/3-1 und SCHU 2828/2-1. GB and TS acknowledge support of the German National Science Foundation (DFG) under the research group grant FOR 1735. MK, DT, KRM, and GB acknowledge financial support by the FP7-ICT Programme of the European Community, under the PASCAL2 Network of Excellence. MK acknowledges a postdoctoral fellowship by the German Research Foundation (DFG), award KL 2698/2-1, and from the Federal Ministry of Science and Education (BMBF) awards 031L0023A and 031B0187B. AN acknowledges support from the Spanish Multiple Sclerosis Network (REEM), of the Instituto de Salud Carlos III (RD12/0032/0011), the Spanish National Institute for Bioinformatics (PT13/0001/0026) the Spanish Government Grant BFU2012-38236 and from FEDER. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 634143 (MedBioinformatics). MK and KRM were financially supported by the Ministry of Education, Science, and Technology, through the National Research Foundation of Korea under Grant R31-10008 (MK, KRM) and BK21 (KRM).

Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer. ; The POPRES data were obtained from dbGaP (accession number # 2038). The Danish National Research Foundation, ERC Starting Grant (260372) to TM-B, and (310372) to MGN, FEDER and Spanish Government Grants BFU2009-13409-C02-02, BFU2012-38236 to AN, BFU2011-28549 to TM-B, BFU2012-34157 to CL-F, ERC (Marie Cure Actions) to MEA, NIH NRSA postdoctoral fellowship (F32GM106656) to CWKC, NIH (R01-HG007089) to JN, NSF postdoctoral fellowship (DBI-1103639) to MDG

A pyrographically decorated gourd, dated to the French Revolution period, has been alleged to contain a handkerchief dipped into the blood of the French king Louis XVI (1754–1793) after his beheading but recent analyses of living males from two Bourbon branches cast doubts on its authenticity. We sequenced the complete genome of the DNA contained in the gourd at low coverage (2.5×) with coding sequences enriched at a higher 7.3× coverage. We found that the ancestry of the gourd's genome does not seem compatible with Louis XVI's known ancestry. From a functional perspective, we did not find an excess of alleles contributing to height despite being described as the tallest person in Court. In addition, the eye colour prediction supported brown eyes, while Louis XVI had blue eyes. This is the first draft genome generated from a person who lived in a recent historical period; however, our results suggest that this sample may not correspond to the alleged king. ; This work is supported by FEDER and Spanish Government grants BFU2012-38236 and the Spanish Multiple Sclerosis Netowrk (REEM) of the Instituto de Salud Carlos III (RD12/0032/0011) to A.N., BFU2011-28549 and ERC Starting Grant (260372) to T.M.-B. and BFU2012-34157 to C.L.-F. and S.C., and a predoctoral fellowship from the Basque Government (DEUI) to I.O