Suchergebnisse

The Iberian Peninsula is a well-delimited geographic region with a rich and complex human history. However, the causes of its genetic structure and past migratory dynamics are not yet fully understood. In order to shed light on them, here we evaluated the gene flow and genetic structure throughout the Iberian Peninsula with spatially explicit modelling applied to a georeferenced genetic dataset composed of genome-wide SNPs from 746 individuals belonging to 17 different regions of the Peninsula. We found contrasting patterns of genetic structure throughout Iberia. In particular, we identified strong patterns of genetic differentiation caused by relevant barriers to gene flow in northern regions and, on the other hand, a large genetic similarity in central and southern regions. In addition, our results showed a preferential north to south migratory dynamics and suggest a sex-biased dispersal in Mediterranean and southern regions. The estimated genetic patterns did not fit with the geographical relief of the Iberian landscape and they rather seem to follow political and linguistic territorial boundaries. ; IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). J.P. and A.M.L. are funded by the Portuguese Government through the FCT fellowship SFRH/BD/97200/2013 and the research contract IF/01262/2014, respectively. M.A. was supported by the "Ramón y Cajal" grant RYC-2015-18241 from the Spanish Government. D.C. was supported by the Spanish grant CGL2016-75389-P (AEI, MINEICO/FEDER, UE), and "Unidad María de Maeztu" funded by the MINECO (MDM-2014-0370) ; SI

Autism Spectrum Disorders (ASD) affect around 1.5% of the global population, which manifest alterations in communication and socialization, as well as repetitive behaviors or restricted interests. ASD is a complex disorder with known environmental and genetic contributors; however, ASD etiology is far from being clear. In the past decades, many efforts have been put into developing new models to study ASD, both in vitro and in vivo. These models have a lot of potential to help to validate some of the previously associated risk factors to the development of the disorder, and to test new potential therapies that help to alleviate ASD symptoms. The present review is focused on the recent advances towards the generation of models for the study of ASD, which would be a useful tool to decipher the bases of the disorder, as well as to conduct drug screenings that hopefully lead to the identification of useful compounds to help patients deal with the symptoms of ASD ; Consellería de Educación, Universidade e Formación Profesional (ED431C 2018/28)//FIS PI19/00809 ISCIII//Xunta de Galicia (Centro singular de investigación de Galicia acreditación 2019–2022) and the European Union (European Regional Development Fund - ERDF) (ED431G 2019/02) ; SI

A large number of new microhaplotype loci were identified in the human genome by applying a directed search with selection criteria emphasizing short haplotype length (<120 nucleotides) and maximum levels of polymorphism in the composite SNPs. From these searches, 107 autosomal microhaplotypes and 11 X chromosome microhaplotypes were selected, with well-spaced autosomal positions to ensure their independence in relationship tests. The 118 microhaplotypes were assembled into a single multiplex assay for the analysis of forensic DNA with massively parallel sequencing (MPS). A single AmpliSeq-adapted primer set was made for Illumina MiSeq and Thermo Fisher Ion S5 MPS platforms and the performance of the assay was comprehensively evaluated in both systems. Five microhaplotypes showed critical sequencing failures in both MPS platforms and were removed, while a further 13 required manual checks and the application of sequence quality thresholds in one or both systems to ensure the successful analysis of low-level DNA in these loci. The targeting of short microhaplotype spans during marker selection, with an average length of 51 nucleotides in the 118 loci, led to a high level of sensitivity for the panel when sequencing the very degraded DNA typically encountered in forensic casework and the identification of missing persons ; The studies reported and authors MdlP, CP, MVL are supported by MAPA: Multiple Allele Polymorphism Analysis (BIO2016-78525-R), a research project funded by the Spanish Research State Agency (AEI), and co-financed with ERDF funds. MdlP is supported by a postdoctoral fellowship awarded by the Consellería de Cultura, Educación e Ordenación Universitaria and the Consellería de Economía, Emprego e Industria of the Xunta de Galicia (ED481B 2017/088). The studies reported have received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 740580 within the framework of the Visible Attributes Through Genomics (VISAGE) Project and Consortium ; SI

The rate of response to pharmacological treatment in Obsessive-compulsive disorder (OCD) oscillates between 40 and 70%. Genetic and environmental factors have been associated with treatment response in OCD. This study analyzes the predictive ability of a polygenic risk score (PRS) built from OCD-risk variants, for treatment response in OCD, and the modulation role of stressful life events (SLEs) at the onset of the disorder. PRSs were calculated for a sample of 103 patients. Yale–Brown Obsessive Compulsive Scale (YBOCS) scores were obtained before and after a 12-week treatment. Regression analyses were performed to analyze the influence of the PRS and SLEs at onset on treatment response. PRS did not predict treatment response. The best predictive model for post-treatment YBOCS (post YBOCS) included basal YBOCS and age. PRS appeared as a predictor for basal and post YBOCS. SLEs at onset were not a predictor for treatment response when included in the regression model. No evidence for PRS predictive ability for treatment response was found. The best predictor for treatment response was age, agreeing with previous literature specific for SRI treatment. Suggestions are made on the possible role of neuroplasticity as a mediator on this association. PRS significantly predicted OCD severity independent on pharmacological treatment. SLE at onset modulation role was not evidenced. Further research is needed to elucidate the genetic and environmental bases of treatment response in OCD. ; This study was supported in part by the Carlos III Health Institute (PI13/01958, PI13/00918, PI14/00413 and PI16/00950); FEDER funds ('A way to build Europe') and by the Agency of University and Research Funding Management of the Catalan Government (2014SGR1672). We also acknowledge support of the Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2017-2021', SEV-2016-0571 and of the Spanish MINECO SAF2013-49108-R Plan Estatal. M.A. was supported by the Secretariat for Universities and Research of the ...

Haplogroup R1b-M269 comprises most Western European Y chromosomes; of its main branches, R1b-DF27 is by far the least known, and it appears to be highly prevalent only in Iberia. We have genotyped 1072 R1b-DF27 chromosomes for six additional SNPs and 17 Y-STRs in population samples from Spain, Portugal and France in order to further characterize this lineage and, in particular, to ascertain the time and place where it originated, as well as its subsequent dynamics. We found that R1b-DF27 is present in frequencies ~40% in Iberian populations and up to 70% in Basques, but it drops quickly to 6–20% in France. Overall, the age of R1b-DF27 is estimated at ~4,200 years ago, at the transition between the Neolithic and the Bronze Age, when the Y chromosome landscape of W Europe was thoroughly remodeled. In spite of its high frequency in Basques, Y-STR internal diversity of R1b-DF27 is lower there, and results in more recent age estimates; NE Iberia is the most likely place of origin of DF27. Subhaplogroup frequencies within R1b-DF27 are geographically structured, and show domains that are reminiscent of the pre-Roman Celtic/Iberian division, or of the medieval Christian kingdoms. ; Funding was provided by the Agencia Estatal de Investigación and Fondo Europeo de Desarollo Regional (FEDER) (grants CGL2013-44351-P, CGL2016-75389-P), by Agència de Gestió d'Ajuts Universitaris i de la Recerca (Generalitat de Catalunya) grant 2014 SGR 866, and by the Basque Government (IT-424-07). FT was supported by the ERC Advanced Grant Agreement No 295733, 'LanGeLin' project ; SI

The early-life exposome influences future health and accelerated biological aging has been proposed as one of the underlying biological mechanisms. We investigated the association between more than 100 exposures assessed during pregnancy and in childhood (including indoor and outdoor air pollutants, built environment, green environments, tobacco smoking, lifestyle exposures, and biomarkers of chemical pollutants), and epigenetic age acceleration in 1,173 children aged 7 years old from the Human Early-Life Exposome project. Age acceleration was calculated based on Horvath's Skin and Blood clock using child blood DNA methylation measured by Infinium HumanMethylation450 BeadChips. We performed an exposure-wide association study between prenatal and childhood exposome and age acceleration. Maternal tobacco smoking during pregnancy was nominally associated with increased age acceleration. For childhood exposures, indoor particulate matter absorbance (PMabs) and parental smoking were nominally associated with an increase in age acceleration. Exposure to the organic pesticide dimethyl dithiophosphate and the persistent pollutant polychlorinated biphenyl-138 (inversely associated with child body mass index) were protective for age acceleration. None of the associations remained significant after multiple-testing correction. Pregnancy and childhood exposure to tobacco smoke and childhood exposure to indoor PMabs may accelerate epigenetic aging from an early age ; The study received funding from the European Community's Seventh Framework Programme (FP7/2007-206) (grant agreement no 308333) (HELIX project), the H2020-EU.3.1.2. - Preventing Disease Programme (grant agreement no 874583) (ATHLETE project), and from the European Union's Horizon 2020 research and innovation programme (grant Agreement number: 733206) (Early Life stressors and Lifecycle Health (LIFECYCLE)). BiB received funding from the Welcome Trust (WT101597MA), from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) ...

Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, implicating XPR1 and phosphate homeostasis in PFBC. ; Lung GO Sequencing Project ; Lung GO Sequencing Project ; Women's Health Initiative (WHI) Sequencing Project ; Broad GO Sequencing Project ; Seattle GO Sequencing Project ; Heart GO Sequencing Project ; United States Department of Health & Human Services ; National Institutes of Health (NIH) - USA ; NIH National Institute of Neurological Disorders & Stroke (NINDS) ; Association Francaise contre les Myopathies ; Ligue Nationale contre le Cancer (Comite de l'Herault) ; Fondation pour la Recherche Medicale ; FEDER European Union Languedoc-Roussillon grant ; National Institute of Neurological Disorders and Stroke ; Informatics Center for Neurogenetics and Neurogenomics ; Fondation pour la Recherche Medicale ; Institut National du Cancer (INCA) France ; Labex GR-Ex ; Labex EpiGenMed ; French National Research Agency (ANR) ; Institut National de la Sante et de la Recherche Medicale (Inserm) ; European Commission ; Instituto de Salud Carlos III (ISCIII) ; INNOPHARMA project MINECO-USC ; Servizo Galego de Saúde (SERGAS) ; National Council for Scientific and Technological Development (CNPq) ; United States Department of Health & Human Services ; National Institutes of Health (NIH) - USA ; NIH National Institute of Mental Health (NIMH) ; United States Department of Health & Human Services ; National Institutes of Health (NIH) - USA ; NIH National Institute of Neurological Disorders & Stroke (NINDS) ; University Hospital of Rouen ; French CNR-MAJ ; United States Department of Health & Human Services ; National Institutes of Health (NIH) - USA ; NIH National Heart Lung & Blood Institute (NHLBI) ; United States Department of Health & Human Services ; National Institutes of Health (NIH) - USA ; NIH National Institute of Mental Health (NIMH) ; United States Department of Health & Human Services ; National Institutes of Health (NIH) - USA ; NIH National Institute of Neurological Disorders & Stroke (NINDS)