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We have genotyped the 58 STRs (27 autosomal, 24 Y-STRs and 7 X-STRs) and 94 autosomal SNPs in Illumina ForenSeq™ Primer Mix A in a sample of 248 men and 143 women from El Salvador, Central America. Regional division (Centro, Oriente, Occidente) showed in almost all cases F values not significantly different from 0, and further analyses were applied only to the undivided, country-wide population. The overall random match probability (RMP) decreased from 6.79 × 10 in length-based genotypes in the 27 autosomal STRs to 1.47 × 10 in repeat-sequence based genotypes. Combining the autosomal loci in this set, RMP reaches 2.97 × 10. In a population genetic analysis, El Salvador showed the lowest F values with US Hispanics both for autosomal and X-STRs; however, it was much closer to Native Americans for the latter than for the former, in accordance with the well-known gender-biased admixture that created most Latin American populations., This work was supported by the Spanish Ministry of Economy and Competitiveness and Agencia Estatal de Investigación (grant numbers CGL2016–75389-P (MINEICO/FEDER, UE), PID2019–106485GB-I00/AEI/10.13039/501100011033 (MINEICO), and “Unidad María de Maeztu” (MDM-2014–0370) to FCal; Agència de Gestió d′Ajuts Universitaris i de la Recerca (Generalitat de Catalunya, grant 2017SGR00702); Agència Catalana de Cooperació al Desenvolupament (ACCD004/17/00019 and ACCD016/18/00031); Fundación Panamericana para el Desarrollo (PADF, No. PRDHD-RFA-R-2017–009). We thank also the Ministry of Health of El Salvador, which, in 2018, allowed us to take samples at their facilities.

Autoinflammatory diseases comprise a wide range of syndromes caused by dysregulation of the innate immune response. They are difficult to diagnose due to their phenotypic heterogeneity and variable expressivity. Thus, the genetic origin of the disease remains undetermined for an important proportion of patients. We aim to identify causal genetic variants in patients with suspected autoinflammatory disease and to test the advantages and limitations of the clinical exome gene panels for molecular diagnosis. Twenty-two unrelated patients with clinical features of autoinflammatory diseases were analyzed using clinical exome sequencing (~4800 genes), followed by bioinformatic analyses to detect likely pathogenic variants. By integrating genetic and clinical information, we found a likely causative heterozygous genetic variant in NFKBIA (p.D31N) in a North-African patient with a clinical picture resembling the deficiency of interleukin-1 receptor antagonist, and a heterozygous variant in DNASE2 (p.G322D) in a Spanish patient with a suspected lupus-like monogenic disorder. We also found variants likely to increase the susceptibility to autoinflammatory diseases in three additional Spanish patients: one with an initial diagnosis of juvenile idiopathic arthritis who carries two heterozygous UNC13D variants (p.R727Q and p.A59T), and two with early-onset inflammatory bowel disease harbouring NOD2 variants (p.L221R and p.A728V respectively). Our results show a similar proportion of molecular diagnosis to other studies using whole exome or targeted resequencing in primary immunodeficiencies. Thus, despite its main limitation of not including all candidate genes, clinical exome targeted sequencing can be an appropriate approach to detect likely causative variants in autoinflammatory diseases., This study was funded by grants SAF2012-35025 and SAF2015-68472-C2-2-R from the Ministerio de Economía y Competitividad (Spain) and FEDER (EU) to FC; RTI2018-096824-B-C22 grant from the Spanish Ministry of Science, Innovation and Universities co-financed by ERDF (FC), by Direcció General de Recerca, Generalitat de Catalunya (2014SGR-866 and 2017SGR-702) to FC, the CERCA Programme, Generalitat de Catalunya (JIA), SAF2015-68472-C2-1-R grant from the Spanish Ministry of Economy and Competitiveness co-financed by European Regional Development Fund (ERDF) (JIA), RTI2018-096824-B-C21 grant from the Spanish Ministry of Science, Innovation and Universities co-financed by ERDF (JIA), and AC15/00027 grant from the Instituto de Salud Carlos III, Transnational Research Projects on Rare Diseases (JIA). LBM is supported by a Formació de personal Investigador fellowship from Generalitat de Catalunya (2018_FI_B00072). MSM is supported by the María de Maetzu Programme (MDM-2014-0370-16-3).

[ES] La enfermedad pulmonar obstructiva crónica (EPOC) es una entidad de presentación heterogénea. Por ello, se han intentado perfilar diferentes fenotipos y endotipos, que permitirían un manejo más diferenciado. El objetivo del proyecto Biomarcadores en la EPOC (BIOMEPOC) es identificar biomarcadores sanguíneos útiles para tipificar mejor a los enfermos. Se analizarán datos clínicos y muestras sanguíneas en un grupo de pacientes y controles sanos. El proyecto constará de fases de prospección y de validación. Se realizarán determinaciones analíticas sanguíneas con técnicas convencionales y de diversas ciencias «ómicas» (transcriptómica, proteómica y metabolómica). Las primeras se realizarán orientadas por hipótesis, mientras que con las segundas se realizará una exploración sin dicho condicionante. Finalmente se realizará un análisis multinivel. En el momento actual se han reclutado 269 pacientes y 83 controles, y se está iniciando el procesamiento de muestras. Con los resultados obtenidos se espera identificar nuevos biomarcadores que, en solitario o combinados, permitan una mejor tipificación de los pacientes., [EN] Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain ‘omics’ (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients.

We have genotyped the 58 STRs (27 autosomal, 24 Y-STRs and 7 X-STRs) and 94 autosomal SNPs in Illumina ForenSeq™ Primer Mix A in 88 Spanish Roma (Gypsy) samples and 143 Catalans. Since this platform is based in massive parallel sequencing, we have used simple R scripts to uncover the sequence variation in the repeat region. Thus, we have found, across 58 STRs, 541 length-based alleles, which, after considering repeat-sequence variation, became 804 different alleles. All loci in both populations were in Hardy-Weinberg equilibrium. FST between both populations was 0.0178 for autosomal SNPs, 0.0146 for autosomal STRs, 0.0101 for X-STRs and 0.1866 for Y-STRs. Combined a priori statistics showed quite large; for instance, pooling all the autosomal loci, the a priori probabilities of discriminating a suspect become 1 − (2.3 × 10−70) and 1 − (5.9 × 10−73), for Roma and Catalans respectively, and the chances of excluding a false father in a trio are 1 − (2.6 × 10−20) and 1 − (2.0 × 10−21). Funding was provided by the Spanish Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarollo Regional (FEDER) (grant CGL2016-75389-P), and by Agència de Gestió d’Ajuts Universitaris i de la Recerca (Generalitat de Catalunya) grant 2014 SGR 866.