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IntroductionIn order to deliver high quality results, detection and elimination of possible analytical interferences, such as lipaemia, is crucial. The aim of this study is to evaluate the efficacy of high-speed centrifugation in eliminating lipaemic interference and to define own lipaemic index (LI) for the studied biochemical analytes. Materials and methodsEvaluated analytes were: albumin, alkaline phosphatase, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), calcium, creatinine, gamma-glutamyltransferase (GGT), glucose, phosphates, total proteins, urea and total bilirubin. Those analytes and LIs have been analysed in duplicate in the Roche Diagnostics-c8000 analyser in samples centrifuged at 3000 rpm/10 minutes in the SL16 (Thermo Scientific, Waltham, USA) centrifuge and according to an own high-speed centrifugation protocol (12,900 rpm/15 minutes) in the MicroCL17R (Thermo Scientific, Waltham, USA) centrifuge. Lipaemia has been measured in each sample. The efficiency of high-speed centrifugation is verified by the Wilcoxon test (P < 0.05). In cases where significant differences are observed, our own LI is calculated. For ALT and AST, it is verified by McNemar test (P < 0.05). For creatinine, both Wilcoxon and McNemar test were applied. ResultsThere were statistically significant differences in analyte concentration before and after high-speed centrifugation for: albumin, creatinine, GGT, glucose, phosphates, urea and total bilirrubin. Own LI is calculated. McNemar test shows statistically significant diferences in the proportion of delivered results before and after high-speed centrifugation in ALT, AST and creatinine. ConclusionsThis study confirms the efficacy of high-speed centrifugation protocol for all the considered analytes, excepting calcium, alkaline phosphatase and total proteins.

Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%). Supported by Generalitat de Catalunya through Departament de Salut (SLT002/16/00174 to URD-Cat consortium) and Departament d’Empresa i Coneixement and the CERCA Program; FP7 and H2020 EU projects RD-Connect, Solve-RD, and EJP-RD grants FP7 305444, H2020 779257, and H2020 825575 for CNAG-CRG; Spanish Ministry of Science and Innovation to the EMBL partnership and through the Instituto de Salud Carlos III grants PT13/0001/0044 and PT17/0009/0019 for CNAG-CRG and grants PI16/01048, PI19/01310, PI18/00451, PI18/00498, and PI21/00935 for IDIBAPS (Instituto Nacional de Bioinformática); ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa grant SEV-2016-0571 (CNAG-CRG) and grant CEX 2018-000806-S (ISGLOBAL); and cofinancing with funds from the European Regional Development Fund by the Spanish Ministry of Science and Innovation corresponding to the Programa Operativo FEDER Plurirregional de España (POPE) 2014 to 2020 and by the Secretaria d’Universitats i Recerca, Departament d’Empresa i Coneixement of the Generalitat de Catalunya corresponding to the Programa Operatiu FEDER de Catalunya 2014 to 2020.

Supplemental material, MSJ851428_supplementary_material for A pharmacogenetic study implicates NINJ2 in the response to Interferon-β in multiple sclerosis by Silvia Peroni, Melissa Sorosina, Sunny Malhotra, Ferdinando Clarelli, Ana Maria Osiceanu, Laura Ferrè, Tina Roostaei, Jordi Rio, Luciana Midaglia, Luisa María Villar, José Carlos Álvarez-Cermeño, Clara Guaschino, Marta Radaelli, Lorena Citterio, Jeannette Lechner-Scott, Nino Spataro, Arcadi Navarro, Vittorio Martinelli, Xavier Montalban, Howard L Weiner, Philip de Jager, Giancarlo Comi, Federica Esposito, Manuel Comabella and Filippo Martinelli-Boneschi in Multiple Sclerosis Journal

From Darwin’s “On the Origin of Species”, many years elapsed before human diseases were considered in an evolutionary framework. Besides theoretical and empirical advances, we are far from the complete understanding of disease aetiology. Highly penetrant disorders with Mendelian inheritance are mostly explained by the mutation-selection balance model, which is insufficient to describe the selective pressures acting on the full set of alleles related to diseases. We show in the first two papers that Next Generation Sequencing (NGS) technologies provide a unique opportunity to investigate variation and contribute to the understanding of the genetic architecture of disease. Besides exploring the role of rare and copy number variants in Parkinson’s disease (PD), we demonstrate the functional relation between Mendelian and idiopathic PD. In the last paper, we report that variation in genes previously related to Mendelian disorders has a more important role in driving complex disease susceptibility than genes associated only to complex diseases., Des de l'Origen de les Espècies de Darwin van passar molts anys abans que les malalties humanes fossin considerades sota un marc evolutiu. Tanmateix, tot i els darrers avenços teòrics i empírics, estem molt lluny de tenir una comprensió completa de l'etiologia de les malalties humanes. Mentre els trastorns altament penetrants amb herència mendeliana poden explicar-se sota un model d’equilibri mutació-selecció, aquest és insuficient per descriure les pressions selectives que actuen sobre tot el conjunt d'al·lels associats a malalties. Mostrem en els dos primers treballs que les noves tecnologies de seqüenciació proporcionen una oportunitat única per investigar la variació i contribuir a la comprensió de l'arquitectura genètica de la malaltia. A més d'explorar el paper de les variants rares i en el nombre de còpies en la malaltia de Parkinson (PD), demostrem la relació funcional entre les formes mendelianes i idiopàtiques d’aquesta malaltia. En el darrer treball, mostrem sota una perspectiva evolutiva i funcional que, en comparació amb la variació genètica en gens associats només a malalties complexes, la variació en gens prèviament relacionats amb trastorns Mendelians sembla tenir un paper clarament més important en la susceptibilitat a la malaltia complexa.

Engelken, Johannes.-- Trabajo presentado en el V Congreso de la Sociedad Española de Biología Evolutiva (SESBE 2016), celebrado en Murcia del 18 al 21 de enero de 2016., Micronutrients possess vital functions at molecular, cellular and physiological levels, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 human liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 SNPs in the same sample set. We detected significant associations between SNP genotypes and eight protein abundances (pQTLs), 10 mRNA levels (eQTLs) and 15 micronutrient concentrations (nutriQTLs). Six of these survived the false discovery rate (FDR) cutoff: i) one pQTL for GPX2 (rs10133290); ii) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and iii) three nutriQTLs: the pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1 GPX3, SLC30A9 and SLC39A8, which are related to zinc and selenium. Overall, this multilayered, integrative study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients.

The analysis of coverage depth in next-generation sequencing data allows the detection of gene dose alterations. We explore the frequency of such structural events in a Spanish cohort of sporadic PD cases. Gene dose alterations were detected with the eXome-Hidden Markov Model (XHMM) software from depth of coverage in resequencing data available for 38 Mendelian and other risk PD loci in 394 individuals (249 cases and 145 controls) and subsequently validated by quantitative PCR. We identified 10 PD patients with exon dosage alterations in PARK2, GBA-GBAP1, and DJ1. Additional functional variants, including 2 novel nonsense mutations (p.Arg1552Ter in LRRK2 and p.Trp90Ter in PINK1), were confirmed by Sanger sequencing. This combined approach disclosed the genetic cause of 12 PD cases. Gene dose alterations related to PD can be correctly identified from targeting resequencing data. This approach substantially improves the detection rate of cases with causal genetic alterations. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

We report here the draft genome sequence of Aeromonas molluscorum 848T, the type strain of this Aeromonas species, which was isolated from wedge shells (Donax trunculus) obtained from a retail market in Barcelona, Spain, in 1997.

We report here the draft genome sequence of Aeromonas molluscorum 848T, the type strain of this Aeromonas species, which was isolated from wedge shells (Donax trunculus) obtained from a retail market in Barcelona, Spain, in 1997. This work was partially funded by grant SAF2011-29239; from the Ministerio de Ciencia e Innovación, Spanish Government; grant 2009SGR-1101 from Direcció General de Recerca, Generalitat de Catalunya; and grant ARZ00F01 from the University of Barcelona