Search

Supergenes are involved in adaptation in multiple organisms, but they are little known in humans. Genomic inversions are the most common mechanism of supergene generation and maintenance. Here, we review the information about two large inversions that are the best examples of potential human supergenes. In addition, we do an integrative analysis of the newest data to understand better their functional effects and underlying genetic changes. We have found that the highly divergent haplotypes of the 17q21.31 inversion of approximately 1.5 Mb have multiple phenotypic associations, with consistent effects in brain-related traits, red and white blood cells, lung function, male and female characteristics and disease risk. By combining gene expression and nucleotide variation data, we also analysed the molecular differences between haplotypes, including gene duplications, amino acid substitutions and regulatory changes, and identifyCRHR1, KANLS1andMAPTas good candidates to be responsible for these phenotypes. The situation is more complex for the 8p23.1 inversion, where there is no clear genetic differentiation. However, the inversion is associated with several related phenotypes and gene expression differences that could be linked to haplotypes specific of one orientation. Our work, therefore, contributes to the characterization of both exceptional variants and illustrates the important role of inversions.This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.

The combined analysis of haplotype panels with phenotype clinical cohorts is a common approach to explore the genetic architecture of human diseases. However, genetic studies are mainly based on single nucleotide variants (SNVs) and small insertions and deletions (indels). Here, we contribute to fill this gap by generating a dense haplotype map focused on the identification, characterization, and phasing of structural variants (SVs). By integrating multiple variant identification methods and Logistic Regression Models (LRMs), we present a catalogue of 35 431 441 variants, including 89 178 SVs (≥50 bp), 30 325 064 SNVs and 5 017 199 indels, across 785 Illumina high coverage (30x) whole-genomes from the Iberian GCAT Cohort, containing a median of 3.52M SNVs, 606 336 indels and 6393 SVs per individual. The haplotype panel is able to impute up to 14 360 728 SNVs/indels and 23 179 SVs, showing a 2.7-fold increase for SVs compared with available genetic variation panels. The value of this panel for SVs analysis is shown through an imputed rare Alu element located in a new locus associated with Mononeuritis of lower limb, a rare neuromuscular disease. This study represents the first deep characterization of genetic variation within the Iberian population and the first operational haplotype panel to systematically include the SVs into genome-wide genetic studies. GCAT|Genomes for Life, a cohort study of the Genomes of Catalonia, Fundació Institut Germans Trias i Pujol (IGTP); IGTP is part of the CERCA Program/Generalitat de Catalunya; GCAT is supported by Acción de Dinamización del ISCIII-MINECO; Ministry of Health of the Generalitat of Catalunya [ADE 10/00026]; Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) [2017-SGR 529]; B.C. is supported by national grants [PI18/01512]; X.F. is supported by VEIS project [001-P-001647] (co-funded by European Regional Development Fund (ERDF), ‘A way to build Europe’); a full list of the investigators who contributed to the generation of the GCAT data is available from www.genomesforlife.com/; Severo Ochoa Program, awarded by the Spanish Government [SEV-2011-00067 and SEV2015-0493]; Spanish Ministry of Science [TIN2015-65316-P]; Innovation and by the Generalitat de Catalunya [2014-SGR-1051 to D.T.]; Agencia Estatal de Investigación (AEI, Spain) [BFU2016-77244-R and PID2019-107836RB-I00]; European Regional Development Fund (FEDER, EU) (to M.C.); Spanish Ministry of Science and Innovation [FPI BES-2016-0077344 to J.V.M.]; C.S. received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement [H2020-MSCA-COFUND-2016-754433]; this study made use of data generated by the UK10K Consortium from UK10K COHORT IMPUTATION [EGAS00001000713]; formal agreement with the Barcelona Supercomputing Center (BSC); this study made use of data generated by the Genome of the Netherlands’ project, which is funded by the Netherlands Organization for Scientific Research [184021007], allowing us to use the GoNL reference panel containing SVs, upon request (GoNL Data Access request 2019203); this study also used data generated by the Haplotype Reference Consortium (HRC) accessed through the European Genome-phenome Archive with the accession numbers EGAD00001002729; formal agreement of the Barcelona Supercomputing Center (BSC) with WTSI; this study made use of data generated by the 1000 Genomes (1000G), accessed through the FTP portal (http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20130502/); this study used the GeneHancer-for-AnnotSV dump for GeneCards Suite Version 4.14, through a formal agreement between the BSC and the Weizmann Institute of Science. Funding for open access charge: GCAT|Genomes for Life, a cohort study of the Genomes of Catalonia, Fundació Institut Germans Trias i Pujol (IGTP); IGTP is part of the CERCA Program/Generalitat de Catalunya; GCAT is supported by Acción de Dinamización del ISCIII-MINECO; Ministry of Health of the Generalitat of Catalunya [ADE 10/00026]; Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) [2017-SGR 529]; B.C. is supported by national grants [PI18/01512]; X.F. is supported by VEIS project [001-P-001647] (co-funded by European Regional Development Fund (ERDF), ‘A way to build Europe’); a full list of the investigators who contributed to the generation of the GCAT data is available from www.genomesforlife.com/; Severo Ochoa Program, awarded by the Spanish Government [SEV-2011-00067 and SEV2015-0493]; Spanish Ministry of Science [TIN2015-65316-P]; Innovation and by the Generalitat de Catalunya [2014-SGR-1051 to D.T.]; [Agencia Estatal de Investigación (AEI, Spain) [BFU2016-77244-R and PID2019-107836RB-I00]; European Regional Development Fund (FEDER, EU) (to M.C.); Spanish Ministry of Science and Innovation [FPI BES-2016-0077344 to J.V.M.]; C.S. received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement [H2020-MSCA-COFUND-2016-754433]; this study made use of data generated by the UK10K Consortium from UK10K COHORT IMPUTATION [EGAS00001000713]; formal agreement with the Barcelona Supercomputing Center (BSC); this study made use of data generated by the Genome of the Netherlands’ project, which is funded by the Netherlands Organization for Scientific Research [184021007], allowing us to use the GoNL reference panel containing SVs, upon request (GoNL Data Access request 2019203); this study also used data generated by the Haplotype Reference Consortium (HRC) accessed through the European Genome-phenome Archive with the accession numbers EGAD00001002729; formal agreement of the Barcelona Supercomputing Center (BSC) with WTSI; this study made use of data generated by the 1000 Genomes (1000G), accessed through the FTP portal (http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20130502/); this study used the GeneHancer-for-AnnotSV dump for GeneCards Suite Version 4.14, through a formal agreement between the BSC and The Weizmann Institute of Science. "Article signat per 21 autors/es: Jordi Valls-Margarit, Iván Galván-Femenía, Daniel Matías-Sánchez, Natalia Blay, Montserrat Puiggròs, Anna Carreras, Cecilia Salvoro, Beatriz Cortés, Ramon Amela, Xavier Farre, Jon Lerga-Jaso, Marta Puig, Jose Francisco Sánchez-Herrero, Victor Moreno, Manuel Perucho, Lauro Sumoy, Lluís Armengol, Olivier Delaneau, Mario Cáceres, Rafael de Cid, David Torrents"

Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung., Andre Franke and David Ellinghaus were supported by a grant from the German Federal Ministry of Education and Research (01KI20197), Andre Franke, David Ellinghaus and Frauke Degenhardt were supported by the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). David Ellinghaus was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). David Ellinghaus, Karina Banasik and Søren Brunak acknowledge the Novo Nordisk Foundation (grant NNF14CC0001 and NNF17OC0027594). Tobias L. Lenz, Ana Teles and Onur Özer were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project numbers 279645989; 433116033; 437857095. Mareike Wendorff and Hesham ElAbd are supported by the German Research Foundation (DFG) through the Research Training Group 1743, "Genes, Environment and Inflammation". This project was supported by a Covid-19 grant from the German Federal Ministry of Education and Research (BMBF; ID: 01KI20197). Luca Valenti received funding from: Ricerca Finalizzata Ministero della Salute RF2016-02364358, Italian Ministry of Health ""CV PREVITAL – strategie di prevenzione primaria cardiovascolare primaria nella popolazione italiana; The European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- and for the project ""REVEAL""; Fondazione IRCCS Ca' Granda ""Ricerca corrente"", Fondazione Sviluppo Ca' Granda ""Liver-BIBLE"" (PR-0391), Fondazione IRCCS Ca' Granda ""5permille"" ""COVID-19 Biobank"" (RC100017A). Andrea Biondi was supported by the grant from Fondazione Cariplo to Fondazione Tettamanti: "Biobanking of Covid-19 patient samples to support national and international research (Covid-Bank). This research was partly funded by a MIUR grant to the Department of Medical Sciences, under the program "Dipartimenti di Eccellenza 2018–2022". This study makes use of data generated by the GCAT-Genomes for Life. Cohort study of the Genomes of Catalonia, Fundació IGTP. IGTP is part of the CERCA Program / Generalitat de Catalunya. GCAT is supported by Acción de Dinamización del ISCIIIMINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529). Marta Marquié received research funding from ant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National RDI Plan and financed by ISCIIISubdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa")., Beatriz Cortes is supported by national grants PI18/01512. Xavier Farre is supported by VEIS project (001-P-001647) (cofunded by European Regional Development Fund (ERDF), “A way to build Europe”). Additional data included in this study was obtained in part by the COVICAT Study Group (Cohort Covid de Catalunya) supported by IsGlobal and IGTP, EIT COVID-19 Rapid Response activity 73A and SR20-01024 La Caixa Foundation. Antonio Julià and Sara Marsal were supported by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). Antonio Julià was also supported the by national grant PI17/00019 from the Acción Estratégica en Salud (ISCIII) and the FEDER. The Basque Biobank is a hospitalrelated platform that also involves all Osakidetza health centres, the Basque government's Department of Health and Onkologikoa, is operated by the Basque Foundation for Health Innovation and Research-BIOEF. Mario Cáceres received Grants BFU2016-77244-R and PID2019-107836RB-I00 funded by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU). Manuel Romero Gómez, Javier Ampuero Herrojo, Rocío Gallego Durán and Douglas Maya Miles are supported by the “Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III” (PI19/01404, PI16/01842, PI19/00589, PI17/00535 and GLD19/00100), and by the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018, COVID-Premed, COVID GWAs). The position held by Itziar de Rojas Salarich is funded by grant FI20/00215, PFIS Contratos Predoctorales de Formación en Investigación en Salud. Enrique Calderón's team is supported by CIBER of Epidemiology and Public Health (CIBERESP), "Instituto de Salud Carlos III". Jan Cato Holter reports grants from Research Council of Norway grant no 312780 during the conduct of the study. Dr. Solligård: reports grants from Research Council of Norway grant no 312769. The BioMaterialBank Nord is supported by the German Center for Lung Research (DZL), Airway Research Center North (ARCN). The BioMaterialBank Nord is member of popgen 2.0 network (P2N). Philipp Koehler has received non-financial scientific grants from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. He is supported by the German Federal Ministry of Education and Research (BMBF)., Oliver A. Cornely is supported by the German Federal Ministry of Research and Education and is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – CECAD, EXC 2030 – 390661388. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping was performed by the Genotyping laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki. This work was supported by grants of the Rolf M. Schwiete Stiftung, the Saarland University, BMBF and The States of Saarland and Lower Saxony. Kerstin U. Ludwig is supported by the German Research Foundation (DFG, LU-1944/3-1). Genotyping for the BoSCO study is funded by the Institute of Human Genetics, University Hospital Bonn. Frank Hanses was supported by the Bavarian State Ministry for Science and Arts. Part of the genotyping was supported by a grant to Alfredo Ramirez from the German Federal Ministry of Education and Research (BMBF, grant: 01ED1619A, European Alzheimer DNA BioBank, EADB) within the context of the EU Joint Programme – Neurodegenerative Disease Research (JPND). Additional funding was derived from the German Research Foundation (DFG) grant: RA 1971/6-1 to Alfredo Ramirez. Philip Rosenstiel is supported by the DFG (CCGA Sequencing Centre and DFG ExC2167 PMI and by SH state funds for COVID19 research). Florian Tran is supported by the Clinician Scientist Program of the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). Christoph Lange and Jan Heyckendorf are supported by the German Center for Infection Research (DZIF). Thorsen Brenner, Marc M Berger, Oliver Witzke und Anke Hinney are supported by the Stiftung Universitätsmedizin Essen. Marialbert Acosta-Herrera was supported by Juan de la Cierva Incorporacion program, grant IJC2018-035131-I funded by MCIN/AEI/10.13039/501100011033. Eva C Schulte is supported by the Deutsche Forschungsgemeinschaft (DFG; SCHU 2419/2-1).

The combined analysis of haplotype panels with phenotype clinical cohorts is a common approach to explore the genetic architecture of human diseases. However, genetic studies are mainly based on single nucleotide variants (SNVs) and small insertions and deletions (indels). Here, we contribute to fill this gap by generating a dense haplotype map focused on the identification, characterization and phasing of structural variants (SVs). By integrating multiple variant identification methods and Logistic Regression models, we present a catalogue of 35,431,441 variants, including 89,178 SVs (≥50bp), 30,325,064 SNVs and 5,017,199 indels, across 785 Illumina high coverage (30X) whole-genomes from the Iberian GCAT Cohort, containing 3.52M SNVs, 606,336 indels and 6,393 SVs in median per individual. The haplotype panel is able to impute up to 14,360,728 SNVs/indels and 23,179 SVs, showing a 2.7-fold increase for SVs compared with available genetic variation panels. The value of this panel for SVs analysis is shown through an imputed rare Alu element located in a new locus associated with mononeuritis of lower limb, a rare neuromuscular disease. This study represents the first deep characterization of genetic variation within the Iberian population and the first operational haplotype panel to systematically include the SVs into genome-wide genetic studies.

Background There is increasing evidence of the importance of copy number variants (CNV) in genetic diversity among individuals and populations, as well as in some common genetic diseases. We previously characterized a common 32-kb insertion/deletion variant of the PSORS4 locus at chromosome 1q21 that harbours the LCE3C and LCE3B genes. This variant allele (LCE3C_LCE3B-del) is common in patients with psoriasis and other autoimmune disorders from certain ethnic groups. Results Using array-CGH (Agilent 244 K) in samples from the HapMap and Human Genome Diversity Panel (HGDP) collections, we identified 54 regions showing population differences in comparison to Africans. We provided here a comprehensive population-genetic analysis of one of these regions, which involves the 32-kb deletion of the PSORS4 locus. By a PCR-based genotyping assay we characterised the profiles of the LCE3C_LCE3B-del and the linkage disequilibrium (LD) pattern between the variant allele and the tag SNP rs4112788. Our results show that most populations tend to have a higher frequency of the deleted allele than Sub-Saharan Africans. Furthermore, we found strong LD between rs4112788G and LCE3C_LCE3B-del in most non-African populations (r2 >0.8), in contrast to the low concordance between loci (r2 Conclusions These results are another example of population variability in terms of biomedical interesting CNV. The frequency distribution of the LCE3C_LCE3B-del allele and the LD pattern across populations suggest that the differences between ethnic groups might not be due to natural selection, but the consequence of genetic drift caused by the strong bottleneck that occurred during “out of Africa” expansion.

Next-generation sequencing technologies expedited research to develop efficient computational tools for the identification of structural variants (SVs) and their use to study human diseases. As deeper data is obtained, the existence of higher complexity SVs in some genomes becomes more evident, but the detection and definition of most of these complex rearrangements is still in its infancy. The full characterization of SVs is a key aspect for discovering their biological implications. Here we present a pipeline (PeSV-Fisher) for the detection of deletions, gains, intra- and inter-chromosomal translocations, and inversions, at very reasonable computational costs. We further provide comprehensive information on co-localization of SVs in the genome, a crucial aspect for studying their biological consequences. The algorithm uses a combination of methods based on paired-reads and read-depth strategies. PeSV-Fisher has been designed with the aim to facilitate identification of somatic variation, and, as such, it is capable of analysing two or more samples simultaneously, producing a list of non-shared variants between samples. We tested PeSV-Fisher on available sequencing data, and compared its behaviour to that of frequently deployed tools (BreakDancer and VariationHunter). We have also tested this algorithm on our own sequencing data, obtained from a tumour and a normal blood sample of a patient with chronic lymphocytic leukaemia, on which we have also validated the results by targeted re-sequencing of different kinds of predictions. This allowed us to determine confidence parameters that influence the reliability of breakpoint predictions. This work was supported by AGAUR (Generalitat de Catalunya, 2009 SGR 1502) (X.E.); CIBERESP (Instituto de Salud Carlos III) (G.E.); ESGI (European Commission, 262055_ESGI) (R.R., X.E.), ENGAGE (European Commission, ENGAGE_201413), TECHGENE (European Commission, TECHGENE_223143), and GEUVADIS (European Commission, 261123_GEUVADIS) (X.E.); NOVADIS (Ministerio de Ciencia y Technologia, SAF2008-00357) (X.E.); Galicia Government Xunta de Galicia (Spain) through the project number 10PXIB918057 (J.M.C.T.); MAEC-AEC1 Predoctoral Fellowship (Ministerio de Asuntos Exteriores y Cooperación, Spain) (A.M.F.); and Ramón y Cajal position and grant BFU2007-60930 (Ministerio de Educación y Ciencia) (M.C.).

Despite many years of study into inversions, very little is known about their functional consequences, especially in humans. A common hypothesis is that the selective value of inversions stems in part from their effects on nearby genes, although evidence of this in natural populations is almost nonexistent. Here we present a global analysis of a new 415-kb polymorphic inversion that is among the longest ones found in humans and is the first with clear position effects. This inversion is located in chromosome 19 and has been generated by non-homologous end joining between blocks of transposable elements with low identity. PCR genotyping in 541 individuals from eight different human populations allowed the detection of tag SNPs and inversion genotyping in multiple populations worldwide, showing that the inverted allele is mainly found in East Asia with an average frequency of 4.7%. Interestingly, one of the breakpoints disrupts the transcription factor gene ZNF257, causing a significant reduction in the total expression level of this gene in lymphoblastoid cell lines. RNA-Seq analysis of the effects of this expression change in standard homozygotes and inversion heterozygotes revealed distinct expression patterns that were validated by quantitative RT-PCR. Moreover, we have found a new fusion transcript that is generated exclusively from inverted chromosomes around one of the breakpoints. Finally, by the analysis of the associated nucleotide variation, we have estimated that the inversion was generated ~40,000–50,000 years ago and, while a neutral evolution cannot be ruled out, its current frequencies are more consistent with those expected for a deleterious variant, although no significant association with phenotypic traits has been found so far., Author Summary Since the discovery of chromosomal inversions almost 100 years ago, how they are maintained in natural populations has been a highly debated issue. One of the hypotheses is that inversion breakpoints could affect genes and modify gene expression levels, although evidence of this came only from laboratory mutants. In humans, a few inversions have been shown to associate with expression differences, but in all cases the molecular causes have remained elusive. Here, we have carried out a complete characterization of a new human polymorphic inversion and determined that it is specific to East Asian populations. In addition, we demonstrate that it disrupts the ZNF257 gene and, through the translocation of the first exon and regulatory sequences, creates a previously nonexistent fusion transcript, which together are associated to expression changes in several other genes. Finally, we investigate the potential evolutionary and phenotypic consequences of the inversion, and suggest that it is probably deleterious. This is therefore the first example of a natural polymorphic inversion that has position effects and creates a new chimeric gene, contributing to answer an old question in evolutionary biology.

In recent years different types of structural variants (SVs) have been discovered in the human genome and their functional impact has become increasingly clear. Inversions, however, are poorly characterized and more difficult to study, especially those mediated by inverted repeats or segmental duplications. Here, we describe the results of a simple and fast inverse PCR (iPCR) protocol for high-throughput genotyping of a wide variety of inversions using a small amount of DNA. In particular, we analyzed 22 inversions predicted in humans ranging from 5.1 kb to 226 kb and mediated by inverted repeat sequences of 1.6–24 kb. First, we validated 17 of the 22 inversions in a panel of nine HapMap individuals from different populations, and we genotyped them in 68 additional individuals of European origin, with correct genetic transmission in ∼12 mother-father-child trios. Global inversion minor allele frequency varied between 1% and 49% and inversion genotypes were consistent with Hardy-Weinberg equilibrium. By analyzing the nucleotide variation and the haplotypes in these regions, we found that only four inversions have linked tag-SNPs and that in many cases there are multiple shared SNPs between standard and inverted chromosomes, suggesting an unexpected high degree of inversion recurrence during human evolution. iPCR was also used to check 16 of these inversions in four chimpanzees and two gorillas, and 10 showed both orientations either within or between species, providing additional support for their multiple origin. Finally, we have identified several inversions that include genes in the inverted or breakpoint regions, and at least one disrupts a potential coding gene. Thus, these results represent a significant advance in our understanding of inversion polymorphism in human populations and challenge the common view of a single origin of inversions, with important implications for inversion analysis in SNP-based studies., Author Summary Inversions have been an evolutionary biology model for almost a century, and recently the discovery of a high amount of structural variation in multiple organisms, including humans, has renewed the interest in them. Since early on, it was shown that they were adaptive and that they were involved in human diseases. However, in humans, the study of inversions has lagged behind due to important limitations in the experimental methods to analyze them. Here, we have optimized a technique for high-throughput validation and genotyping of inversions mediated by inverted repeats. By genotyping 17 of these inversions in a diverse sample of human individuals, including many of European origin and several non-human primates, we have carried out the most complete genotyping effort of human inversions to date. The results of our study indicate that a high proportion of these inversions are recurrent and have occurred multiple times during evolution. This represents an example of the plasticity of the genome and opens a new paradigm in the study of inversions, challenging the common view that inversions have a unique origin.

One of the most used techniques to study structural variation at a genome level is paired-end mapping (PEM). PEM has the advantage of being able to detect balanced events, such as inversions and translocations. However, inversions are still quite difficult to predict reliably, especially from high-throughput sequencing data. We simulated realistic PEM experiments with different combinations of read and library fragment lengths, including sequencing errors and meaningful base-qualities, to quantify and track down the origin of false positives and negatives along sequencing, mapping, and downstream analysis. We show that PEM is very appropriate to detect a wide range of inversions, even with low coverage data. However, ≥% of inversions located between segmental duplications are expected to go undetected by the most common sequencing strategies. In general, longer DNA libraries improve the detectability of inversions far better than increments of the coverage depth or the read length. Finally, we review the performance of three algorithms to detect inversions--SVDetect, GRIAL, and VariationHunter--, identify common pitfalls, and reveal important differences in their breakpoint precisions. These results stress the importance of the sequencing strategy for the detection of structural variants, especially inversions, and offer guidelines for the design of future genome sequencing projects.

In order to contribute with more integrative strategies for better identify areas of high conservation priority we study the coupling of physical and biological processes that sustain a deep subpopulation of the most caught sea urchin (Loxechinus albus) worldwide and its associated epibenthic community over a bathymetric depression in southern Chile, which is surrounded by intensive anthropic activities. We used a remotely operated vehicle (ROV) to characterize the epibenthic community (organisms > 15 mm long) and substrate, up to a depth of 112 m in a submarine hole. Additionally, a combination of a towed and a moored Acoustic Doppler current Profiler (ADCP) was used to characterize current patterns. We found evidence that physical mechanisms transport and retain macro and micro material in the bottom of the hollow, and they contribute to homogenizing the habitat along the entire bathymetric gradient. These coupled processes allow i) that several species expand their bathymetric distribution range, ii) the existence of nursery areas for fishes, iii) that characteristic grazers in shallow habitats colonize greater depths, where filter feeders or DOM consumers generally represent the typical epifauna. We hypothesize that coupling of physical and biological processes on this bathymetric depression are key for bring on Loxechinus albus along the entire bathymetric gradient, who in turn is key to the community structure of the hollow. Given that this particular habitat is surrounded by intensive anthropic activities (eg. salmon aquaculture, mussel aquaculture, fishing, port) and a city, we suggest: Firstly, that monitoring should be undertaken in order to observe biodiversity changes in the bathymetric gradient, since it could be an indicator of conservation status. Secondly, that a proposal should be formulated to consider this zone as a Marine Protected Area.

La utilidad de la planificación familiar, ayudará a las familias en la formación del nuevo ser, capacitándolos para ser más eficientes al tener un mayor apoyo entre padres. La principal tarea a partir de la lectura del artículo, es ayudar a reducir los embarazos no deseados, el abandono de los niños y a su vez los abortos. La planificación familiar es un componente esencial en el cuidado de la salud primaria y reproductiva. Si la práctica sexual se da sin planificación ni protección necesaria, se convierte en una amenaza que deriva en problemas como: deserción escolar, altas tasas de fecundidad por embarazos no planificados, o en otros casos terminan en aborto o muertes maternas e infantiles, como también enfermedades de transmisión sexual. La planificación familiar es considerada importante al facilitar a las parejas los métodos y medios con los cuales puedan tener hogares más estables y felices.

The patterns of abundance, composition, biomass and vertical migration of zooplankton in short-time scales ( 10 of total dry weight (mg m −3 ) of zooplankton biomass was moderate but significant in both locations. Biomass estimated from biological samples was higher in the mixed station and determined by euphausiids. Copepods were the most abundant group in both stations. Acoustic methods were a useful technique to understand the detailed patterns of migratory strategies of zooplankton and to help estimate zooplankton biomass and abundance in the inner waters of southern Chile.

The influence of oceanographic features and moon phases on ichthyoplankton assemblages in a temperate nearshore rocky reef off El Quisco Bay, central Chile, was assessed during austral spring–summer 2015–2016 using Bongo nets. Wind direction was predominantly south-west, and ocean temperature increased gradually during the study period, fluctuating between 11.6°C and 17.7°C. A relatively cold period (from late September to early December, 12.42 ± 0.64°C) was distinguished from a relatively warmer phase (from mid-December to February, 13.56 ± 1.08°C). Nearshore ichthyoplankton was composed of 13,700 individuals, belonging to 43 taxa. Larval Strangomera bentincki (Clupeidae) were collected in high numbers between late September and late October with peaks during full moon and first quarter (maximum = 734 ind. 100 m−3); larval Engraulis ringens (Engraulidae) was most abundant between late October and late December 2015, with peaks during the third quarter and full moon. Principal Component Analysis o...

We describe a seiche process based on current, temperature, and sea-level data obtained from the Reloncaví fjord (41.6° S, 72.5° W) in southern Chile. We combined 4 months of acoustic Doppler current profiler (ADCP) data with sea-level, temperature, and wind time series to analyze the dynamics of low-frequency (periods > 1 day) internal oscillations in the fjord. Additionally, seasonal conductivity, temperature, and depth (CTD) data from 19 along-fjord stations were used to characterize the seasonality of the density field. The density profiles were used to estimate the internal long-wave phase speed (c) using two approximations: (1) a simple reduced gravity model (RGM) and (2) a continuously stratified model (CSM). No major seasonal changes in c were observed using either approximation (e.g., the CSM yielded 0.73 c −1 for mode 1). The natural internal periods (TN) were estimated using Merian's formula for a simple fjord-like basin and the above phase speeds. Estimated values of TN varied between 2.9 and 3.5 days and were highly consistent with spectral peaks observed in the along-fjord currents and temperature time series. We conclude that these oscillations were forced by the wind stress, despite the moderate wind energy. Wind conditions at the end of winter gave us an excellent opportunity to explore the damping process. The observed damping time (Td) was relatively long (Td = 9.1 days).

Rhesus macaque is an Old World monkey that shared a common ancestor with human ∼25 Myr ago and is an important animal model for human disease studies. A deep understanding of its genetics is therefore required for both biomedical and evolutionary studies. Among structural variants, inversions represent a driving force in speciation and play an important role in disease predisposition. Here we generated a genome-wide map of inversions between human and macaque, combining single-cell strand sequencing with cytogenetics. We identified 375 total inversions between 859 bp and 92 Mbp, increasing by eightfold the number of previously reported inversions. Among these, 19 inversions flanked by segmental duplications overlap with recurrent copy number variants associated with neurocognitive disorders. Evolutionary analyses show that in 17 out of 19 cases, the Hominidae orientation of these disease-associated regions is always derived. This suggests that duplicated sequences likely played a fundamental role in generating inversions in humans and great apes, creating architectures that nowadays predispose these regions to disease-associated genetic instability. Finally, we identified 861 genes mapping at 156 inversions breakpoints, with some showing evidence of differential expression in human and macaque cell lines, thus highlighting candidates that might have contributed to the evolution of species-specific features. This study depicts the most accurate fine-scale map of inversions between human and macaque using a two-pronged integrative approach, such as single-cell strand sequencing and cytogenetics, and represents a valuable resource toward understanding of the biology and evolution of primate species.

Despite the interest in characterizing all genomic variation, the presence of large repeats at the breakpoints of many structural variants hinders their analysis. This is especially problematic in the case of inversions, since they are balanced changes without gain or loss of DNA. Here we tested novel linkage-based droplet digital PCR (ddPCR) assays on 20 inversions ranging from 3.1 to 742 kb and flanked by long inverted repeats (IRs) of up to 134 kb. Among these, we validated 13 inversions predicted by different genome-wide techniques. In addition, we have generated new experimental human population information across 95 African, European and East-Asian individuals for 16 of them, including four already known inversions for which there were no high-throughput methods to determine directly the orientation, like the well-characterized 17q21 inversion. Through comparison with previous data, independent replicates and both inversion breakpoints, we have demonstrated that the technique is highly accurate and reproducible. Most of the studied inversions are frequent and widespread across continents, showing a negative correlation with genetic length. Moreover, all except two show clear signs of being recurrent, and the new data allowed us to define more clearly the factors affecting recurrence levels and estimate the inversion rate across the genome. Finally, thanks to the generated genotypes, we have been able to check inversion functional effects in multiple tissues, validating gene expression differences reported before for two inversions and finding new candidate associations. Our work therefore provides a tool to screen these and other complex genomic variants quickly in a large number of samples for the first time, highlighting the importance of direct genotyping to assess their potential consequences and clinical implications.

Seasonal data on temperature, salinity, dissolved oxygen (DO) and chlorophyll, combined with meteorological and river discharge time series, were used to describe the oceanographic conditions of the Reloncaví fjord (41°35′ S, 72°20′ W). The winds in the fjord valley mainly blow down-fjord during the winter, reinforcing the upper layer outflow, whereas the winds blow predominantly up-fjord during the spring and summer, contrary to the upper layer outflow. The fjord, with a deep sill at the mouth, was well stratified year-round and featured a thin surface layer of brackish water with mean salinities between 10.4 ± 1.4 (spring) and 13.2 ± 2.5 (autumn). The depth of the upper layer changed slightly among the different studied seasons but remained at 4.5 m near the mouth. This upper layer presented a mean outflow (Q1) of 3185 ± 223 m3 s−1, which implies a flushing time of 3 days for this layer. The vertical salt flux was ∼ 37 tons of salt per second, similar to the horizontal salt flux observed in the upper layer. These estimates will contribute to better management of the aquaculture in this region.

SUMMARYInversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about inversions in the human genome due to the difficulty of their detection. Here, thanks to the development of a new high-throughput genotyping method, we have performed a complete study of a representative set of 45 common human polymorphic inversions. Most inversions promoted by homologous recombination occur recurrently both in humans and great apes and, since they are not tagged by SNPs, they are missed by genome-wide association studies. Furthermore, there is an enrichment of inversions showing signatures of positive or balancing selection, diverse functional effects, such as gene disruption and gene-expression changes, or association with phenotypic traits. Therefore, our results indicate that the genome is more dynamic than previously thought and that human inversions have important functional and evolutionary consequences, making possible to determine for the first time their contribution to complex traits.

El objetivo de este estudio fue determinar la variacion temporal de las condiciones oceanograficas, ictioplancton y sus ectoparasitos en aguas costeras marinas. Se realizaron 30 muestreos de ictioplancton entre el 11 de octubre 2012 y el 5 de junio 2014 a lo largo de una transecta desde 0,25 km hasta 4,5 km de la costa frente a Montemar, Bahia Valparaiso, Chile central. Se identifico un total de 5.553 larvas de peces, pertenecientes a 37 taxa. Las larvas de peces mas abundantes originadas de desove pelagico fueron la sardina comun Strangomera bentincki (abundancia relativa= 26,39%), anchoveta Engraulis ringens (8,94%), y el mictofido Hygophum bruuni (7,72%); las especies mas abundantes originadas de posturas bentonicas fueron la borrachilla Scartichthys viridis (15,77%), el cachudito Hypsoblennius sordidus (8,27%) y el pejesapo Gobiesox marmoratus (7,06%). Las larvas de peces mas parasitadas provinieron de posturas bentonicas, los pejesapos G. marmoratus (prevalencia= 9,63%) y Sicyases sanguineus (0,54%), el tomollo Auchenionchus variolosus (1,72%), y el trombollito de tres aletas Helcogrammoides cunninghami (3,28%). La unica especie con desove pelagico que presento ectoparasitos fue el blanquillo Prolatilus jugularis (0,57%). Las larvas de peces con ectoparasitos mostraron una disminucion en abundancia con la distancia a la costa; S. bentincki, H. bruuni (desove pelagico) o S. viridis (postura bentonica) fueron mas abundantes a 2,0 km de la costa. Los ectoparasitos fueron identificados como Trifur spp. (Copepoda: Pennellidae) y Caligus spp. (Copepoda: Caligidae), siendo los penelidos los mas frecuentes (1 a 3 parasitos por larva). El 94 y 88% de los penelidos y caligidos, respectivamente, fue recolectado en la estacion mas costera. Durante los periodos de mayor prevalencia de ectoparasitos en las larvas de peces, el agua de mar estuvo verticalmente estratificada con una profundizacion a fines de otono y un ascenso en verano de la picnoclina desde mar afuera hacia la costa. Por lo tanto, los resultados sugieren que las larvas de peces originadas de posturas bentonicas son parasitadas mas frecuentemente y que las condiciones fisicas de la columna de agua pueden favorecer tanto la retencion costera como la infestacion por ectoparasitos en las aguas mas cercanas a la costa.

Polymorphic inversions are a type of structural variants that are difficult to analyze owing to their balanced nature and the location of breakpoints within complex repeated regions. So far, only a handful of inversions have been studied in detail in humans and current knowledge about their possible functional effects is still limited. However, inversions have been related to phenotypic changes and adaptation in multiple species. In this review, we summarize the evidences of the functional impact of inversions in the human genome. First, given that inversions have been shown to inhibit recombination in heterokaryotes, chromosomes displaying different orientation are expected to evolve independently and this may lead to distinct gene-expression patterns. Second, inversions have a role as disease-causing mutations both by directly affecting gene structure or regulation in different ways, and by predisposing to other secondary arrangements in the offspring of inversion carriers. Finally, several inversions show signals of being selected during human evolution. These findings illustrate the potential of inversions to have phenotypic consequences also in humans and emphasize the importance of their inclusion in genome-wide association studies.

Time series of acoustic backscatter and vertical velocity profiles were obtained at three sites along a Chilean fjord with the purpose of determining dominant structures of vertical migrations of the sound scattering layer. Ancillary data obtained with stratified net samples indicated that the sound scattering layer may have been dominated by euphausiids and decapods. Therefore, distributions of acoustic backscatter anomalies and vertical velocities were attributed to vertical migrations of predominantly these organisms. Migration patterns were dominated by twilight excursions in which organisms swam toward the water surface at sunset, spent 100 m). This migration strategy can also be termed ‘semidiel migration’ as two double excursions were linked to light levels. The reasons for this twilight migration remain uncertain. But it is possible that the up and down motion around sunset was related to predation avoidance, hunger–satiation state, ontogeny, seaward transport evasion, or reaction to the environmental shock from the pycnocline, or a combination of all or some of them. In contrast, the sunrise double excursion was probably linked to feeding requirements by organisms that need to spend the day at great depth with no food available. This study demonstrated the existence of semidiel patterns throughout the fjord and through prolonged periods. In addition, identification of this pattern by acoustic backscatter was complemented by direct vertical velocity measurements. It is proposed that twilight vertical migration is a common strategy in Chilean fjords.

The prevalence of asthma and obesity is increasing worldwide, and obesity is a well-documented risk factor for asthma. The mechanisms underlying this association and parallel time trends remain largely unknown but genetic factors may be involved. Here, we report on a common ~0.45 Mb genomic inversion at 16p11.2 that can be accurately genotyped via SNP array data. We show that the inversion allele protects against the joint occurrence of asthma and obesity in five large independent studies (combined sample size of 317 cases and 543 controls drawn from a total of 5,809 samples; combined OR = 0.48, p = 5.5 × 10(-6)). Allele frequencies show remarkable worldwide population stratification, ranging from 10% in East Africa to 49% in Northern Europe, consistent with discordant and extreme genetic drifts or adaptive selections after human migration out of Africa. Inversion alleles strongly correlate with expression levels of neighboring genes, especially TUFM (p = 3.0 × 10(-40)) that encodes a mitochondrial protein regulator of energy balance and inhibitor of type 1 interferon, and other candidates for asthma (IL27) and obesity (APOB48R and SH2B1). Therefore, by affecting gene expression, the ~0.45 Mb 16p11.2 inversion provides a genetic basis for the joint susceptibility to asthma and obesity, with a population attributable risk of 39.7%. Differential mitochondrial function and basal energy balance of inversion alleles might also underlie the potential selection signature that led to their uneven distribution in world populations.

The growing catalogue of structural variants in humans often overlooks inversions as one of the most difficult types of variation to study, even though they affect phenotypic traits in diverse organisms. Here, we have analysed in detail 90 inversions predicted from the comparison of two independently assembled human genomes: the reference genome (NCBI36/HG18) and HuRef. Surprisingly, we found that two thirds of these predictions (62) represent errors either in assembly comparison or in one of the assemblies, including 27 misassembled regions in HG18. Next, we validated 22 of the remaining 28 potential polymorphic inversions using different PCR techniques and characterized their breakpoints and ancestral state. In addition, we determined experimentally the derived allele frequency in Europeans for 17 inversions (DAF = 0.01-0.80), as well as the distribution in 14 worldwide populations for 12 of them based on the 1000 Genomes Project data. Among the validated inversions, nine have inverted repeats (IRs) at their breakpoints, and two show nucleotide variation patterns consistent with a recurrent origin. Conversely, inversions without IRs have a unique origin and almost all of them show deletions or insertions at the breakpoints in the derived allele mediated by microhomology sequences, which highlights the importance of mechanisms like FoSTeS/MMBIR in the generation of complex rearrangements in the human genome. Finally, we found several inversions located within genes and at least one candidate to be positively selected in Africa. Thus, our study emphasizes the importance of careful analysis and validation of large-scale genomic predictions to extract reliable biological conclusions.

The relationships between the distribution of different zooplankton and ichthyoplankton stages and physical and chemical variables were studied using samples and data (CTD profiles, ADCP and current meter measurements, nutrients, mesozooplankton, ichthyoplankton) obtained from different strata during two 24-h cycles at two oceanographic stations in a Chilean Patagonian gulf during the CIMAR 10-Fiordos cruise (November, 2004). A station located at the Chacao Channel was dominated by tidal mixing and small increments in surface stratification during high tides, leading to decreased nutrient availability. This agreed with short periods of increased phytoplankton abundance during slack waters at the end of flood currents. Increases in larval density for all zooplankton and ichthyoplankton taxa corresponded to the flooding phases of the tidal cycle. When the larval density data were fit to a sinusoidal model, the regression coefficients were high, suggesting that tides are important features that modulate short-term variations in plankton abundance. All larvae did not vary synchronously with the tidal phase; rather, time lags were observed among species. The abundances of older individuals of the copepodite Rhincalanus nasutus and all zoea stages of the squat lobster Munida gregaria increased during night flood tides, whereas younger stages increased during daytime flood tides. At a station located at the Queullin Pass, which was dominated by vertical stratification patterns, the variations in peak larval density were better fitted to the semi-diurnal sea level fluctuations. Other evidence indicated internal tides below the pycnocline, which could promote larval transport in deeper layers. In the overall picture that emerges from this study, planktonic organisms from different habitats and phylogenetic origins seem to respond to the local tidal regimes. In some cases, this response might be beneficial, transporting these individuals inshore to areas that are rich in food during the peak biological production season.

The spatial and temporal distribution of Dinophysis spp. in a fjord in southern Chile (43°47′S–72°56′W) was studied through experiments performed in a seasonal and intratidal timescales. Seasonal variability was studied through monthly experiments performed between January 2005 and February 2006. Intratidal variability was explored through two 24-h ADCP (acoustic Doppler current profiler) current measurement experiments combined with biological sampling, in order to assess the effect of flow patterns on Dinophysis spp. distribution. We found four species of Dinophysis , which included D. acuminata and D. acuta . The former was the most abundant species in the two samplings, whereas D. acuta was only found in low concentrations near the head of fjord. The persistent saline stratification and the increased temperature during spring–summer were well associated with the increase of D. acuminata cellular concentrations inner Pitipalena Fjord. There, higher concentrations of D. acuminata were observed around the pycnocline in narrow temperature (11.19–12.52 °C) and salinity (19.75–22.59 psu) ranges. During intratidal experiments, decreases in shear instabilities in the up-fjord direction were accompanied by increases in D. acuminata concentrations (maximum 332 cells L −1 in the pycnocline). Our results suggest that the diel variability observed for D. acuminata at the Pitipalena Fjord is mainly influenced by the tidal effect and vertical density gradients (maximum 4.77 sigma-t m −1 ), which was evidenced by the vertical movement of the pycnocline (between 5 and 10 m depth) during the tidal semidiurnal cycle.

León, R., Castro, L. R., and Cáceres, M. 2008. Dispersal of Munida gregaria (Decapoda: Galatheidae) larvae in Patagonian channels of southern Chile. – ICES Journal of Marine Science, 65: 1131–1143. The dispersal of Munida gregaria larvae in Chilean Patagonian channels was assessed in spring 2002 and 2003, and winter 2003. In winter 2003, zoea I was the most abundant stage in all channels and there were no larval stages older than zoea IV. In spring 2002 and 2003, there were six larval stages in all channels, and the greater abundance of older larvae suggested that reproduction takes place in winter and larval development in spring. Further, analysis of spatial distribution by stage revealed that early zoeae moved seawards. Generalized Additive Models analyses showed that most larval stages were temperature-dependent, and that the salinity range of the youngest zoea was wider than that of older larvae and post-larvae, coinciding with an ontogenetic distribution change from estuary to shelf. Residual flows determined with an acoustic Doppler current profiler revealed two layers of opposite flow: the shallowest layer moved seawards and the deeper layer onshore. The surface layer was wider in spring than in winter because of seasonal increase in fresh-water input. The dispersal pattern of M. gregaria consisted of an inner channel larval release in winter, followed by an along-channel larval drift and subsequent export to the shelf in spring. The mechanism by which juveniles return to the channels seemed to be associated with the onshore subsurface flow.

Alternative splicing is a powerful mechanism affording extensive proteomic and regulatory diversity from a limited repertoire of genes. However, the extent to which alternative splicing has contributed to the evolution of primate species-specific characteristics has not been assessed previously. Using comparative genomics and quantitative microarray profiling, we performed the first global analysis of alternative splicing differences between humans and chimpanzees. Surprisingly, 6%–8% of profiled orthologous exons display pronounced splicing level differences in the corresponding tissues from the two species. Little overlap is observed between the genes associated with alternative splicing differences and the genes that display steady-state transcript level differences, indicating that these layers of regulation have evolved rapidly to affect distinct subsets of genes in humans and chimpanzees. The alternative splicing differences we detected are predicted to affect diverse functions including gene expression, signal transduction, cell death, immune defense, and susceptibility to diseases. Differences in expression at the protein level of the major splice variant of GlutathioneS-transferase omega-2 (GSTO2), which functions in the protection against oxidative stress and is associated with human aging-related diseases, suggests that this enzyme is less active in human cells compared with chimpanzee cells. The results of this study thus support an important role for alternative splicing in establishing differences between humans and chimpanzees.

Genomic plasticity of human chromosome 8p23.1 region is highly influenced by two groups of complex segmental duplications (SDs), termed REPD and REPP, that mediate different kinds of rearrangements. Part of the difficulty to explain the wide range of phenotypes associated with 8p23.1 rearrangements is that REPP and REPD are not yet well characterized, probably due to their polymorphic status. Here, we describe a novel primate-specific gene family, named FAM90A (family with sequence similarity 90), found within these SDs. According to the current human reference sequence assembly, the FAM90A family includes 24 members along 8p23.1 region plus a single member on chromosome 12p13.31, showing copy number variation (CNV) between individuals. These genes can be classified into subfamilies I and II, which differ in their upstream and 5′-untranslated region sequences, but both share the same open reading frame and are ubiquitously expressed. Sequence analysis and comparative fluorescence in situ hybridization studies showed that FAM90A subfamily II suffered a big expansion in the hominoid lineage, whereas subfamily I members were likely generated sometime around the divergence of orangutan and African great apes by a fusion process. In addition, the analysis of the Ka/Ks ratios provides evidence of functional constraint of some FAM90A genes in all species. The characterization of the FAM90A gene family contributes to a better understanding of the structural polymorphism of the human 8p23.1 region and constitutes a good example of how SDs, CNVs and rearrangements within themselves can promote the formation of new gene sequences with potential functional consequences.

The use of high-density oligonucleotide arrays to measure the expression levels of thousands of genes in parallel has become commonplace. To take further advantage of the growing body of data, we developed a method, termed “GeSNP,” to mine the detailed hybridization patterns in oligonucleotide array expression data for evidence of genetic variation. To demonstrate the performance of the algorithm, the hybridization patterns in data obtained previously from SAMP8/Ta, SAMP10/Ta, and SAMR1/Ta inbred mice and from humans and chimpanzees were analyzed. Genes with consistent strain-specific and species-specific hybridization pattern differences were identified, and ∼90% of the candidate genes were independently confirmed to harbor sequence differences. Importantly, the quality of gene expression data was also improved by masking the probes of regions with putative sequence differences between species and strains. To illustrate the application to human disease groups, data from an inflammatory bowel disease study were analyzed. GeSNP identified sequence differences in candidate genes previously discovered in independent association and linkage studies and uncovered many promising new candidates. This approach enables the opportunistic extraction of genetic variation information from new or pre-existing gene expression data obtained with high-density oligonucleotide arrays.

El propósito de este artículo es hacer la descripción de un caso clínico donde se observa una convergencia entre el diagnóstico de TDAH e intento suicida, en ausencia de otras enfermedades psiquiátricas comórbidas, describiendo los antecedentes y el proceso de evaluación.Se trata de un paciente de 10 años de edad, con diagnóstico de TDAH (de acuerdo a los criterios clínicos del DSM IV TR), quien es hospitalizado al presentar intento suicida de alta letalidad por ahorcamiento en ausencia de comorbilidad psiquiátrica alguna, evaluado clínicamente, usando múltiples fuentes de información y por medio de escalas clinimétricas.A pesar de que la tasa de TDAH es alta en poblaciones con ideación, intentos y suicidio completado, (casi el doble que los controles)(1), son relativamente pocas las investigaciones que se han realizado de dicha asociación y además suelen intentar explicar la suicidalidad mediante la psicopatología comórbida (Trastornos afectivos, de ansiedad, de personalidad, abuso de sustancias), sin cuestionar la relación TDAH-riesgo suicida como mecanismo explicativo de forma independiente. La disfunción ejecutiva que se presenta en el TDAH, particularmente, la impulsividad, pudiera estudiarse como un posible mecanismo mediador en el riesgo suicida.

Thrombospondins are extracellular-matrix glycoproteins implicated in the control of synaptogenesis and neurite growth. Previous microarray studies suggested that one gene of this family, thrombospondin 4 (THBS4), was upregulated during human brain evolution. Using independent techniques to examine thrombospondin expression patterns in adult brain samples, we report approximately 6-fold and approximately 2-fold greater expression of THBS4 and THBS2 messenger RNA (mRNA), respectively, in human cerebral cortex compared with chimpanzees and macaques, with corresponding differences in protein levels. In humans and chimpanzees, thrombospondin expression differences were observed in the forebrain (cortex and caudate), whereas the cerebellum and most nonbrain tissues exhibited similar levels of the 2 mRNAs. Histological examination revealed THBS4 mRNA and protein expression in numerous pyramidal and glial cells in the 3 species but humans also exhibited very prominent immunostaining of the synapse-rich cortical neuropil. In humans, additionally, THBS4 antibodies labeled beta-amyloid containing plaques in Alzheimer's cases and some control cases. This is the first detailed characterization of gene-expression changes in human evolution that involve specific brain regions, including portions of cerebral cortex. Increased expression of thrombospondins in human brain evolution could result in changes in synaptic organization and plasticity, and contribute to the distinctive cognitive abilities of humans, as well as to our unique vulnerability to neurodegenerative disease.

The inlets of southern Chile are characterized by a well-defined pycnocline which, acting in concert with the biological characteristics of larvae, is believed to influence planktonic lar- val distribution. Here, we assessed the effects of stratified flow over a sill on the spatial abundance and distribution of epineustonic competent larvae of Concholepas concholepas. We used measure- ments of velocity profiles using an Acoustic Doppler Current Profiler (ADCP), intensive plankton col- lections combined with simultaneous conductivity, temperature and depth (CTD) profiles, monitoring of the pycnocline depth, and temperature records from moored thermistors. Evidence of Bernoulli aspiration and an intratidal transient front was observed over the sill from CTD data and an echo- sounder trace. ADCP measurements showed intensified recirculation in the residual flow over the sill. This oceanographic feature coincided with high abundances of epineustonic competent larvae of C. concholepas over the sill area. We found evidence indicating that physical mechanisms related to sill processes can influence epineustonic competent larval distribution in a stratified system. We also propose a conceptual model that brings together larval behaviour and stratified flow patterns to explain the rise of epineustonic larvae to the surface and larval aggregation over a sill.

Measurements of velocity and density profiles were used to describe the tidal and mean flow structure across and along a sill in Refugio Channel, a fjord-like inlet in Southern Chile (43.9°S). These are the first oceanographic measurements of any kind effected in Refugio Channel. Current profiles were obtained with a 307.2-kHz acoustic Doppler current profiler during two semidiurnal cycles along a repeated triangular circuit. Two along-channel transects formed the sides of the triangle that crossed the sill and were identified as the western and eastern transects. One cross-channel transect, the base of the triangle, was located on the seaward side of the sill. Density profiles were obtained at the corners of the triangle. The longitudinal mean flow in the western transect showed a two-layer exchange structure over the landward side of the sill. The structure of net seaward flow at the surface and landward flow at depth was disrupted by the sill in such a way that over the seaward side of the sill, only seaward flow was observed throughout the water column. This likely resulted from the blocking of landward net flow by the sill. In the eastern transect, two-layer exchange dominated over most of the transect and was consistent with the observed density profiles. Over the seaward side of the sill, a surface layer, ∼10m deep, flowed landward as a third layer. This feature should have been caused by river input further seaward (to the north) and produced a surface convergence region over the sill. In terms of tidal flows, the greatest tidal current amplitudes were 40cm s−1 over the sill as the flow accelerated through the reduced cross-sectional area of the channel. Near-surface flow convergences were identified over both along-channel transects.

Syncytin 1 is one of the best known examples of recent acquisition of a new gene from an endogenous retrovirus (HERV) in the human genome and has been implicated in placental physiology. Within primates, Syncytin 1 is conserved in all hominoids but has not been characterized in Old World monkeys (OWMs). In this study, we investigated the status of Syncytin 1 in 14 hominoid and OWM species. We show that although the HERV-W provirus responsible for the origin of this gene was present in the genome of the most recent common ancestor of hominoids and OWMs, Syncytin 1 is inactive in OWMs. In addition, we were able to determine that the evolution of Syncytin 1 in hominoids involved an accumulation of amino acid changes and showed signatures of both positive and purifying selection. Our results indicate that Syncytin 1 is indeed a hominoid-specific gene and illustrate the complex and dynamic process associated with the origin of new genes.