Publications by authors named "Núria Bonet"

7 Publications

  • Page 1 of 1

Genome-wide postnatal changes in immunity following fetal inflammatory response.

FEBS J 2021 Apr 24;288(7):2311-2331. Epub 2020 Oct 24.

Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.

The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). One of the mechanisms contributing to such a risk is a postnatal intermittent or sustained systemic inflammation (ISSI) following FIR. The link between prenatal and postnatal systemic inflammation is supported by the presence of well-established inflammatory biomarkers in the umbilical cord and peripheral blood. However, the extent of molecular changes contributing to this association is unknown. Using RNA sequencing and mass spectrometry proteomics, we profiled the transcriptome and proteome of archived neonatal dried blood spot (DBS) specimens from 21 ELGANs. Comparing FIR-affected and unaffected ELGANs, we identified 782 gene and 27 protein expression changes of 50% magnitude or more, and an experiment-wide significance level below 5% false discovery rate. These expression changes confirm the robust postnatal activation of the innate immune system in FIR-affected ELGANs and reveal for the first time an impairment of their adaptive immunity. In turn, the altered pathways provide clues about the molecular mechanisms triggering ISSI after FIR, and the onset of perinatal brain injury. DATABASES: EGAS00001003635 (EGA); PXD011626 (PRIDE).
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http://dx.doi.org/10.1111/febs.15578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049052PMC
April 2021

Length and repeat-sequence variation in 58 STRs and 94 SNPs in two Spanish populations.

Forensic Sci Int Genet 2017 09 16;30:66-70. Epub 2017 Jun 16.

Institut de Biologia Evolutiva (UPF-CSIC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain. Electronic address:

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. F 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) and 1-(5.9×10), for Roma and Catalans respectively, and the chances of excluding a false father in a trio are 1-(2.6×10) and 1-(2.0×10).
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http://dx.doi.org/10.1016/j.fsigen.2017.06.006DOI Listing
September 2017

An assessment of a massively parallel sequencing approach for the identification of individuals from mass graves of the Spanish Civil War (1936-1939).

Electrophoresis 2016 10 5;37(21):2841-2847. Epub 2016 Sep 5.

Genomics Core Facility, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Catalonia, Spain.

Next-generation sequencing technologies have opened new opportunities in forensic genetics. Here, we assess the applicability and performance of the MiSeq FGx™ & ForenSeq™ DNA Signature Prep Kit (Illumina) for the identification of individuals from the mass graves of the Spanish Civil War (1936-1939). The main limitations for individual identification are the low number of possible first-degree living relatives and the high levels of DNA degradation reported in previous studies. Massively parallel sequencing technologies enabling the analysis of hundreds of regions and prioritizing short length amplicons constitute a promising tool for this kind of approaches. In this study, we first explore the power of this new technology to detect first- and second-degree kinship given different scenarios of DNA degradation. Second, we specifically assess its performance in a set of low DNA input samples previously analyzed with CE technologies. We conclude that this methodology will allow identification of up to second-degree relatives, even in situations with low sequencing performance and important levels of allele drop-out; it is thus a technology that resolves previous drawbacks and that will allow a successful approximation to the identification of remains.
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http://dx.doi.org/10.1002/elps.201600180DOI Listing
October 2016

Signatures of Evolutionary Adaptation in Quantitative Trait Loci Influencing Trace Element Homeostasis in Liver.

Mol Biol Evol 2016 Mar 17;33(3):738-54. Epub 2015 Nov 17.

Institute of Evolutionary Biology (CSIC-UPF), Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain

Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, 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 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) 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. Overall, this detailed 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.
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http://dx.doi.org/10.1093/molbev/msv267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760079PMC
March 2016

No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

PLoS One 2015 17;10(9):e0135983. Epub 2015 Sep 17.

Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.

While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135983PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574704PMC
May 2016

Changes in circulating microRNAs are associated with childhood obesity.

J Clin Endocrinol Metab 2013 Oct 8;98(10):E1655-60. Epub 2013 Aug 8.

MD, PhD, Section of Diabetes, Endocrinology, and Nutrition. Hospital "Dr Josep Trueta" of Girona, Carretera de França s/n, 17007 Girona, Spain.

Context: Circulating microRNAs (miRNAs) are valuable biomarkers of metabolic diseases and potential therapeutic targets in this field.

Objective: Our objective was to define the circulating pattern of miRNAs in childhood obesity. DESIGN, SETTINGS, AND MAIN OUTCOME MEASURE: The genome-wide circulating miRNA profile was assessed by RT-PCR in 10 boys (5 lean and 5 obese children). The most relevant miRNAs were cross-sectionally validated in 85 lean versus 40 obese children (63 boys and 62 girls) and longitudinally evaluated in samples from the same children when they were ≈ 7 and ≈ 10 years old (23 boys and 22 girls).

Results: The cross-sectional validation study disclosed that 15 specific circulating miRNAs were significantly deregulated in prepubertal obesity, including the decreased miR-221 and miR-28-3p and increased concentrations in plasma of miR-486-5p, miR-486-3p, miR-142-3p, miR-130b, and miR-423-5p (all P < .0001). The circulating concentration of these miRNAs was significantly associated with body mass index and other measures of obesity such as percent fat mass, waist, regional fat distribution and with laboratory parameters such as homeostasis model assessment of insulin resistance, high-molecular-weight adiponectin, C-reactive protein, and circulating lipids in concordance with anthropometric associations. Plasma concentrations of 10 of these circulating miRNAs changed significantly and differently during the 3-year follow-up in children who increased or decreased their normalized weight.

Conclusion: This study provides the first evidence that circulating miRNAs are deregulated in prepubertal obese children. Thus, the very early detection of an abnormal circulating miRNA profile may be a promising strategy to identify obese children who may suffer from metabolic abnormalities.
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http://dx.doi.org/10.1210/jc.2013-1496DOI Listing
October 2013