Rodriguez-Santiago B.,University Pompeu Fabra |
Rodriguez-Santiago B.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer |
Malats N.,CSIC - National Center for Metallurgical Research |
Rothman N.,U.S. National Cancer Institute |
And 26 more authors.
American Journal of Human Genetics | Year: 2010
Mosaicism is defined as the coexistence of cells with different genetic composition within an individual, caused by postzygotic somatic mutation. Although somatic mosaicism for chromosomal abnormalities is a well-established cause of developmental and somatic disorders and has also been detected in different tissues, its frequency and extent in the adult normal population are still unknown. We provide here a genome-wide survey of mosaic genomic variation obtained by analyzing Illumina 1M SNP array data from blood or buccal DNA samples of 1991 adult individuals from the Spanish Bladder Cancer/EPICURO genome-wide association study. We found mosaic abnormalities in autosomes in 1.7% of samples, including 23 segmental uniparental disomies, 8 complete trisomies, and 11 large (1.5-37 Mb) copy-number variants. Alterations were observed across the different autosomes with recurrent events in chromosomes 9 and 20. No case-control differences were found in the frequency of events or the percentage of cells affected, thus indicating that most rearrangements found are not central to the development of bladder cancer. However, five out of six events tested were detected in both blood and bladder tissue from the same individual, indicating an early developmental origin. The high cellular frequency of the anomalies detected and their presence in normal adult individuals suggest that this type of mosaicism is a widespread phenomenon in the human genome. Somatic mosaicism should be considered in the expanding repertoire of inter- and intraindividual genetic variation, some of which may cause somatic human diseases but also contribute to modifying inherited disorders and/or late-onset multifactorial traits. © 2010 The American Society of Human Genetics. All rights reserved.
Gonzalez J.R.,Center for Research in Environmental Epidemiology |
Gonzalez J.R.,Hospital Del Mar Research Institute IMIM |
Gonzalez J.R.,Research Center Biomedica en Red en Epidemiologia y Salud Publica |
Gonzalez J.R.,Autonomous University of Barcelona |
And 45 more authors.
American Journal of Human Genetics | Year: 2014
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. © 2014 The American Society of Human Genetics.
Vandenplas O.,Center Hospitalier University Of Mont Godinne |
Wiszniewska M.,University of Lodz |
Raulf M.,Ruhr University Bochum |
De Blay F.,University of Strasbourg |
And 18 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014
The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: (i) definite IIA, that is acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed-onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Docampo E.,Genomics and Disease Group |
Docampo E.,University Pompeu Fabra |
Docampo E.,Institute Hospital Del Mar dInvestigacions Mediques IMIM |
Docampo E.,Research Center Biomedica en Red en Epidemiologia y Salud Publica |
And 36 more authors.
Pain | Year: 2014
Fibromyalgia (FM) is a highly disabling syndrome defined by a low pain threshold and a permanent state of pain. The mechanisms explaining this complex disorder remain unclear, and its genetic factors have not yet been identified. With the aim of elucidating FM genetic susceptibility factors, we selected 313 FM cases having low comorbidities, and we genotyped them on the Illumina 1 million duo array. Genotypic data from 220 control women (Illumina 610k array) was obtained for genome-wide association scan (GWAS) analysis. Copy number variants in FM susceptibility were analyzed by array comparative genomic hybridization (aCGH) experiments on pooled samples using the Agilent 2 × 400K platform. No single nucleotide polymorphism (SNP) reached GWAS association threshold, but 21 of the most associated SNPs were chosen for replication in 952 cases and 644 controls. Four of the SNPs selected for replication showed a nominal association in the joint analysis, and rs11127292 (MYT1L) was found to be associated to FM with low comorbidities (P = 4.28 × 10-5, odds ratio [95% confidence interval] = 0.58 [0.44-0.75]). aCGH detected 5 differentially hybridized regions. They were followed up, and an intronic deletion in NRXN3 was demonstrated to be associated to female cases of FM with low levels of comorbidities (P =.021, odds ratio [95% confidence interval] = 1.46 [1.05-2.04]). Both GWAS and aCGH results point to a role for the central nervous system in FM genetic susceptibility. If the proposed FM candidate genes were further validated in replication studies, this would highlight a neurocognitive involvement in agreement with latest reports. © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Valero A.,Hospital Clnic |
Valero A.,Research Center Biomedica en Red en Enfermedades Respiratorias |
Ferrer M.,Institute Municipal DInvestigacio Medica IMIM IMAS |
Ferrer M.,Research Center Biomedica en Red en Epidemiologia y Salud Publica |
And 14 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2010
Background: Allergic rhinitis (AR) is a common disease with major socioeconomic burden and a significant impact on quality of life. Objective: The aim of this study was to discriminate between moderate and severe AR patients whether receiving treatment or not, using a modified criterion of allergic rhinitis and its impact on asthma (ARIA) classification. Methods: The modified ARIA severity classification (J Allergy Clin Immunol, 120, 2007, 359) categorizes AR as mild (no items affected), moderate (1-3 items affected), and severe (all four items affected). We applied these criteria to 1666 treated and 1058 untreated AR patients and compared their symptoms total four-symptom score (T4SS) and quality of life (ESPRINT-15), according to their clinical severity. Results: Allergic rhinitis clinical status was significantly worse (P<0.001) in treated than in untreated patients. For both treated and untreated patients, T4SS and ESPRINT-15 Quality of life scores were significantly worse (P<0.001) in severe than in moderate patients. Conclusions: The modified ARIA severity classification is a useful clinical tool to discriminate moderate from severe AR among both treated and untreated patients. © 2010 John Wiley & Sons A/S.
Pardo M.,University of Santiago de Compostela |
Pardo M.,CIBER ISCIII |
Crujeiras A.B.,University of Santiago de Compostela |
Crujeiras A.B.,CIBER ISCIII |
And 33 more authors.
International Journal of Endocrinology | Year: 2014
FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor. © 2014 María Pardo et al.
Coscolla M.,University of Valencia |
Coscolla M.,Research Center Biomedica en Red en Epidemiologia y Salud Publica |
Coscolla M.,Swiss Tropical and Public Health Institute |
Fenollar J.,Centro Salud Publica |
And 3 more authors.
Emerging Infectious Diseases | Year: 2010
From 1999 through 2005 in Alcoi, Spain, incidence of legionellosis was continually high. Over the next 4 years, incidence was lower, but an increase in July 2009 led health authorities to declare an epidemic outbreak. A molecular epidemiology investigation showed that the allelic profiles for all Legionella pneumophila samples from the 2009 outbreak patients were the same, thus pointing to a common genetic origin for their infections, and that they were identical to that of the organism that had caused the previous outbreaks. Spatial-temporal and sequence-based typing analyses indicated a milling machine used in street asphalt repaving and its water tank as the most likely sources. As opposed to other machines used for street cleaning, the responsible milling machine used water from a natural spring. When the operation of this machine was prohibited and cleaning measures were adopted, infections ceased.
Firdessa R.,Armauer Hansen Research Institute |
Firdessa R.,University of Würzburg |
Berg S.,Animal Health and Veterinary Laboratories Agency |
Hailu E.,Armauer Hansen Research Institute |
And 30 more authors.
Emerging Infectious Diseases | Year: 2013
Molecular typing of 964 specimens from patients in Ethiopia with lymph node or pulmonary tuberculosis showed a similar distribution of Mycobacterium tuberculosis strains between the 2 disease manifestations and a minimal role for M. bovis. We report a novel phylogenetic lineage of M. tuberculosis strongly associated with the Horn of Africa.
Bracho M.A.,Centro Superior Of Investigacion En Salud Publica |
Bracho M.A.,Research Center Biomedica en Red en Epidemiologia y Salud Publica |
Gonzalez-Candelas F.,Research Center Biomedica en Red en Epidemiologia y Salud Publica |
Gonzalez-Candelas F.,University of Valencia |
And 3 more authors.
Emerging Infectious Diseases | Year: 2011
Hand, foot, and mouth disease (HFMD), a common disease caused by enteroviruses (EVs), usually affects children. Clustered and sporadic HFMD cases, followed by onychomadesis (nail shedding), occurred during summer and fall 2008 in Valencia, Spain. Fecal samples from onychomadesis patients, who did or did not have previous HFMD, and from healthy children exposed to onychomadesis patients tested positive for EV. The complete viral protein 1 capsid gene sequence was obtained for typing and phylogenetic analysis. Two EV serotypes, coxsackievirus A10 and coxsackievirus B1 (CVB1), were mainly detected as a monoinfection or co-infection in a childcare center where an onychomadesis outbreak occurred. On the basis of our results, and detection of CVB1 in 2 other contemporary onychomadesis outbreaks in childcare centers in Spain, we propose that mixed infection of an EV serotype that causes HFMD, plus the serotype CVB1, could explain the emergence after HFMD of onychomadesis, a rare and late complication.