Suchergebnisse

Artículo de 7 páginas sobre secuencación de genomas que incluye tablas de estadísticas, gráficos de correlación e histogramas. ; Each day, as the amount of genomic data and bioinformatics resources grows, researchers are increasingly challenged with selecting the most appropriate approach to analyze their data. In addition, the opportunity to undertake comparative genomic analyses is growing rapidly. This is especially true for fungi due to their small genome sizes (i.e., mean 1C=44.2Mb). Given these opportunities and aiming to gain novel insights into the evolution of mutualisms, we focus on comparing the quality of whole genome assemblies for fungus-growing ants cultivars (Hymenoptera: Formicidae: Attini) and a free-living relative. Our analyses reveal that currently available methodologies and pipelines for analyzing whole-genome sequence data need refining. By using different genome assemblers, we show that the genome assembly size depends on what software is used. This, in turn, impacts gene number predictions, with higher gene numbers correlating positively with genome assembly size. Furthermore, the majority of fungal genome size data currently available are based on estimates derived from whole-genome assemblies generated from short-read genome data, rather than from the more accurate technique of flow cytometry. Here, we estimated the haploid genome sizes of three ant fungal symbionts by flow cytometry using the fungus Pleurotus ostreatus (Jacq.) P. Kumm. (1871) as a calibration standard. We found that published genome sizes based on genome assemblies are 2.5- to 3-fold larger than our estimates based on flow cytometry. We, therefore, recommend that flow cytometry is used to precalibrate genome assembly pipelines, to avoid incorrect estimates of genome sizes and ensure robust assemblies. ; P.W.K. received funding from CAPES-PrInt (Grant #88887.468939/2019-00) and J.P. benefited from a Ramon y Cajal Fellowship (RYC-2017-2274) from the government of Spain. ; Abstract Results and Discussion Supplementary Material Acknowledgments Literature Cited Supplementary data

Funding text 1 We thank all the study subjects for their valuable participation, the staff from all studies, and the participating physicians. Participants in the INTERVAL randomized controlled trial were recruited with the active collaboration of NHS Blood and Transplant England (www.nhsbt.nhs.uk), which has supported fieldwork and other elements of the trial. DNA extraction and genotyping were co-funded by the National Institute for Health Research (NIHR), the NIHR BioResource (http://bioresource.nihr.ac.uk/) and the NIHR Cambridge Biomedical Research Centre (BRC) [*]. The academic coordinating centre for INTERVAL was supported by core funding from NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024), UK Medical Research Council (MR/L003120/1), British Heart Foundation (SP/09/002; RG/13/13/30194; RG/ 18/13/33946) and the NIHR Cambridge BRC [*]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. A complete list of the investigators and contributors to the INTERVAL trial is provided in reference87. The academic coordinating centre would like to thank blood donor centre staff and blood donors for participating in the INTERVAL trial. Professor John Danesh holds a British Heart Foundation Professorship and a National Institute for Health Research Senior Investigator Award. Steven Bell and Dragana Vuckovic were funded by the NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024). Stephen Kaptoge is funded by a BHF Program Grant (RG/18/13/33946). Will Astle, Joanna Howson, and Tao Jiang are funded by the NIHR Cambridge BRC. Angela M. Wood and Elias Allara are supported by the EC-Innovative Medicines Initiative (BigData@Heart). Praveen Surendran is supported by a Rutherford Fund Fellowship from the Medical Research Council grant MR/S003746/1. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. The Novo Nordisk Foundation (NNF14CC0001 and NNF17OC0027594). The Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115881 (RHAPSODY) (Karina Banasik and Søren Brunak). The Danish Administrative Regions; The Danish Administrative Regions' Bio-and Genome Bank; The authors thank all the blood banks in Denmark for both collecting and contributing data to this study. Danish Blood Donor Research Fund. Aarhus University, Copenhagen University Hospital Research Fund. View less Funding text 2 The authors declare the following competing interests: Henrik Ullum received an unrestricted research grant from Novartis. Cristian Erikstrup received an unrestricted research grant from Abbott. Søren Brunak reports grants from Innovation Fund Denmark, grants from Novo Nordisk Foundation during the conduct of the study; and personal fees from Intomics A/S and Proscion A/S, outside the submitted work. John Danesh sits on the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010); the Steering Committee of UK Biobank (since 2011); the MRC International Advisory Group (ING) member, London (since 2013); the MRC High Throughput Science 'Omics Panel Member, London (since 2013); the Scientific Advisory Committee for Sanofi (since 2013); the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis; and the Astra Zeneca Genomics Advisory Board (2018). Adam S. Butterworth has received grants outside of this work from AstraZeneca, Biogen, BioMarin, Bioverativ, Merck, and Novartis and personal fees from Novartis. For the authors who are affiliated with deCODE genetics/Amgen, we declare competing financial interests as employees. Publisher Copyright: © 2021, The Author(s). ; Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation. ; Peer reviewed

Im vorliegenden Beitrag fragt der Autor nach den ökonomischen Gründen für die Anwerbung von ausländischen Arbeitskräften seit dem Ende des 19. Jahrhunderts und stellt diese dem politisch-administrativen Alltag und der Einstellung der deutschen Mehrheitsgesellschaft gegenüber. Läßt sich an der Geschichte der Ausländerbeschäftigung, der Anwesenheit von Millionen von ethnisch Nichtdeutschen, die bis zur Mitte des 20. Jahrhunderts in Deutschland vorherrschende Ideologie des Nationalismus untersuchen oder gar dokumentieren? Prägen nationalistische Verhaltensmuster den Umgang mit der "Gastarbeiterfrage" in der demokratischen Bundesrepublik? Der Autor kommt zu der Schlußfolgerung, daß die Anwesenheit von Angehörigen verschiedener Ethnien in Deutschland auf Widerspruch in Öffentlichkeit, Politik und Administration stieß und den Alltag der Ausländerbeschäftigung prägte. Das politische Primat der ethnischen Homogenität beeinträchtigte die ökonomische Effizienz der Beschäftigung ausländischer Arbeitskräfte, im Extremfall bis zur Vernichtung menschlicher Arbeitskraft. Diese Denkstrukturen finden sich auch im Umgang mit den "Gastarbeitern" in der Bundesrepublik wieder. (psz)

This work has been financially supported by the Plan Nacional de I+D+I 2013-2016/FEDER (PI15/00892 to M.F.F. and A.F.F.), the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Miguel Servet contract CP11/00131 to A.F.F.); the Asturias Regional Government (GRUPIN14-052 to M.F.F.); FICYT (A.C. and M.G.); the Ministry of Economy and Competitiveness of Spain (J.R.T., Juan de la Cierva fellowship FJCI-2015-26965, V.L., Juan de la Cierva fellowship IJCI-2015-23316); Fundación Científica de la AECC (to R.G.U.); FINBA-ISPA (R.F.P.); IUOPA (G.F.B. and C.M.) and Fundación Ramón Areces (M.F.F.). A.F.F. is also financially supported by the Ministry of Economy and Competitiveness of Spain, the European Regional Development Fund (FEDER) and the Programa Retos de la Sociedad (RTC-2015-3393-1). The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain.

The ongoing controversy surrounding direct-to-consumer (DTC) personal genomic tests intensified last year when the U.S. Government Accountability Office (GAO) released results of an undercover investigation of four companies that offer such testing. Among their findings, they reported that some of their donors received DNA-based predictions that conflicted with their actual medical histories. We aimed to more rigorously evaluate the relationship between DTC genomic risk estimates and self-reported disease by leveraging data from the Scripps Genomic Health Initiative (SGHI). We prospectively collected self-reported personal and family health history data for 3,416 individuals who went on to purchase a commercially available DTC genomic test. For 5 out of 15 total conditions studied, we found that risk estimates from the test were significantly associated with self-reported family and/or personal health history. The 5 conditions, included Graves' disease, Type 2 Diabetes, Lupus, Alzheimer's disease, and Restless Leg Syndrome. To further investigate these findings, we ranked each of the 15 conditions based on published heritability estimates and conducted post-hoc power analyses based on the number of individuals in our sample who reported significant histories of each condition. We found that high heritability, coupled with high prevalence in our sample and thus adequate statistical power, explained the pattern of associations observed. Our study represents one of the first evaluations of the relationship between risk estimates from a commercially available DTC personal genomic test and self-reported health histories in the consumers of that test.

The THSC/TREX-2 complex of Saccharomyces cerevisiae mediates the anchoring of transcribed genes to the nuclear pore, linking transcription elongation with mRNA export and genome stability, as shown for specific reporters. However, it is still unknown whether the function of TREX-2 is global and the reason for its relevant role in genome integrity. Here, by studying two TREX-2 representative subunits, Thp1 and Sac3, we show that TREX-2 has a genome-wide role in gene expression. Both proteins show similar distributions along the genome, with a gradient disposition at active genes that increases towards the 3 end. Thp1 and Sac3 have a relevant impact on the expression of long, G+C-rich and highly transcribed genes. Interestingly, replication impairment detected by the genome-wide accumulation of the replicative Rrm3 helicase is increased preferentially at highly expressed genes in the thp1Δ and sac3Δ mutants analyzed. Therefore, our work provides evidence of a function of TREX-2 at the genome-wide level and suggests a role for TREX-2 in preventing transcription– replication conflicts, as a source of genome instability derived from a defective messenger ribonucleoprotein particle (mRNP) biogenesis. ; Spanish Ministry of Economy and Competitiveness [BFU2010-16372]; Junta de Andalucía [CVI4567 and P12/BIO-1238]; European Union (FEDER); and a JAE predoctoral training grant from the Spanish Research Council (CSIC) [to J.M.S-P.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BFU2010-16372]. ; Peer reviewed

Protein and membrane trafficking pathways are critical for cell and tissue homeostasis. Traditional genetic and biochemical approaches have shed light on basic principles underlying these processes. However, the list of factors required for secretory pathway function remains incomplete, and mechanisms involved in their adaptation poorly understood. Here, we present a powerful strategy based on a pooled genome-wide CRISPRi screen that allowed the identification of new factors involved in protein transport. Two newly identified factors, TTC17 and CCDC157, localized along the secretory pathway and were found to interact with resident proteins of ER-Golgi membranes. In addition, we uncovered that upon TTC17 knockdown, the polarized organization of Golgi cisternae was altered, creating glycosylation defects, and that CCDC157 is an important factor for the fusion of transport carriers to Golgi membranes. In conclusion, our work identified and characterized new actors in the mechanisms of protein transport and secretion and opens stimulating perspectives for the use of our platform in physiological and pathological contexts. ; S.J. Popa acknowledges support from a Wellcome Trust PhD studentship (109152/z/15/z). S.E. Stewart acknowledges support from a Biotechnology and Biological Sciences Research Council Future Leader Fellowship (BB/P010911/1). F. Campelo acknowledges financial support from the Spanish Ministry of Economy and Competitiveness ("Severo Ochoa" program for Centres of Excellence in RD [SEV-2015-0522], FIS2015-63550-R, FIS2017-89560-R, and BFU2015-73288-JIN, AEI/FEDER/UE), Fundació Privada Cellex, and the Generalitat de Catalunya through the CERCA program. A. Ashok acknowledges support from a La Caixa Foundation fellowship. J. Villeneuve acknowledges support from a Marie Curie fellowship within the the European Union's Horizon 2020 research and innovation program (842919). D.C. Rubinsztein is grateful for support from the UK Dementia Research Institute (funded by the Medical Research Council, Alzheimer's Research UK, and the Alzheimer's Society) and the Roger de Spoelberch Foundation.

Despite being the fourth largest island in the Mediterranean basin, the genetic variation of Corsica has not been explored as exhaustively as Sardinia, which is situated only 11 km South. However, it is likely that the populations of the two islands shared, at least in part, similar demographic histories. Moreover, the relative small size of the Corsica may have caused genetic isolation, which, in turn, might be relevant under medical and translational perspectives. Here we analysed genome wide data of 16 Corsicans, and integrated with newly (33 individuals) and previously generated samples from West Eurasia and North Africa. Allele frequency, haplotype-based, and ancient genome analyses suggest that although Sardinia and Corsica may have witnessed similar isolation and migration events, the latter is genetically closer to populations from continental Europe, such as Northern and Central Italians. ; We thank all volunteers who donated their DNA samples. We would like to thank Bayazit Yunusbayev for helpful discussions, Viljo Soo for his help in genotyping and Tuuli Reisberg for assistance in data management. Computational analyses were performed at the High Performance Computing Center of the University of Tartu. This research was supported by institutional research funding IUT (IUT24-1) of the Estonian Ministry of Education and Research (ET, EP); the Estonian Research Council grants PUT (PRG243) (EP, MM) and PUT (PUT1339) (AK); the European Union through the European Regional Development Funds with projects No. 2014-2020.4.01.16-0030 (MM, FM) and No. 2014-2020.4.01.15-0012 (MM); the European Union through Horizon 2020 grant no. 810645 (MM); the University of Pavia strategic theme "Towards a governance model for international migration: an interdisciplinary and diachronic perspective" (MIGRAT-IN-G) (OS); the Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Program (2018–2022), Dept. of Biology and Biotechnology "L. Spallanzani", University of Pavia (AR and OS).

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).

The AdaptMap consortium. ; [Background]: Patterns of homozygosity can be influenced by several factors, such as demography, recombination, and selection. Using the goat SNP50 BeadChip, we genotyped 3171 goats belonging to 117 populations with a worldwide distribution. Our objectives were to characterize the number and length of runs of homozygosity (ROH) and to detect ROH hotspots in order to gain new insights into the consequences of neutral and selection processes on the genome-wide homozygosity patterns of goats. ; [Results]: The proportion of the goat genome covered by ROH is, in general, less than 15% with an inverse relationship between ROH length and frequency i.e. short ROH ( 0.20) FROH values. For populations from Asia, the average number of ROH is smaller and their coverage is lower in goats from the Near East than in goats from Central Asia, which is consistent with the role of the Fertile Crescent as the primary centre of goat domestication. We also observed that local breeds with small population sizes tend to have a larger fraction of the genome covered by ROH compared to breeds with tens or hundreds of thousands of individuals. Five regions on three goat chromosomes i.e. 11, 12 and 18, contain ROH hotspots that overlap with signatures of selection. ; [Conclusions]: Patterns of homozygosity (average number of ROH of 77 and genome coverage of 248 Mb; FROH < 0.15) are similar in goats from different geographic areas. The increased homozygosity in local breeds is the consequence of their small population size and geographic isolation as well as of founder effects and recent inbreeding. The existence of three ROH hotspots that co-localize with signatures of selection demonstrates that selection has also played an important role in increasing the homozygosity of specific regions in the goat genome. Finally, most of the goat breeds analysed in this work display low levels of homozygosity, which is favourable for their genetic management and viability. ; Funding for FB was provided by the Ensminger Endowment, Hatch and State of Iowa Funding. Part of this research was funded by project AGL2016-76108-R awarded by the Spanish Ministry of Economy and Competitiveness. Tainã Figueiredo Cardoso was funded with a fellowship from the CAPES Foundation-Coordination of Improvement of Higher Education, Ministry of Education of the Federal Government of Brazil. ; Peer reviewed

AbstractPrevious genetic studies on hair morphology focused on the overall morphology of the hair using data collected by self-report or researcher observation. Here, we present the first genome-wide association study (GWAS) of a micro-level quantitative measure of hair curvature. We compare these results to GWAS results obtained using a macro-level classification of observable hair curvature performed in the same sample of twins and siblings of European descent. Observational data were collected by trained observers, while quantitative data were acquired using an Optical Fibre Diameter Analyser (OFDA). The GWAS for both the observational and quantitative measures of hair curvature resulted in genome-wide significant signals at chromosome 1q21.3 close to the trichohyalin (TCHH) gene, previously shown to harbor variants associated with straight hair morphology in Europeans. All genetic variants reaching genome-wide significance for both GWAS (quantitative measure lead single-nucleotide polymorphism [SNP] rs12130862, p = 9.5 × 10–09; observational measure lead SNP rs11803731, p = 2.1 × 10–17) were in moderate to very high linkage disequilibrium (LD) with each other (minimum r2 = .45), indicating they represent the same genetic locus. Conditional analyses confirmed the presence of only one signal associated with each measure at this locus. Results from the quantitative measures reconfirmed the accuracy of observational measures.