ORCID Profile
0000-0002-3146-7899
Current Organisation
Universidad del Norte
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Publisher: Springer Science and Business Media LLC
Date: 24-11-2015
DOI: 10.1038/MP.2015.172
Publisher: Elsevier BV
Date: 07-2008
Publisher: Springer Science and Business Media LLC
Date: 29-01-2019
DOI: 10.1038/S41398-019-0396-7
Abstract: Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 ( LPHN3 ) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal s les from disparate regions of the world ( n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large s le of in iduals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2011
DOI: 10.1038/TP.2011.14
Publisher: Springer Science and Business Media LLC
Date: 11-04-2012
Publisher: Wiley
Date: 21-12-2010
DOI: 10.1002/AJMG.B.30969
Publisher: The Royal Society
Date: 27-04-2016
Abstract: Plant litter breakdown is a key ecological process in terrestrial and freshwater ecosystems. Streams and rivers, in particular, contribute substantially to global carbon fluxes. However, there is little information available on the relative roles of different drivers of plant litter breakdown in fresh waters, particularly at large scales. We present a global-scale study of litter breakdown in streams to compare the roles of biotic, climatic and other environmental factors on breakdown rates. We conducted an experiment in 24 streams encompassing latitudes from 47.8° N to 42.8° S, using litter mixtures of local species differing in quality and phylogenetic ersity (PD), and alder ( Alnus glutinosa ) to control for variation in litter traits. Our models revealed that breakdown of alder was driven by climate, with some influence of pH, whereas variation in breakdown of litter mixtures was explained mainly by litter quality and PD. Effects of litter quality and PD and stream pH were more positive at higher temperatures, indicating that different mechanisms may operate at different latitudes. These results reflect global variability caused by multiple factors, but unexplained variance points to the need for expanded global-scale comparisons.
Publisher: BMJ
Date: 02-12-2010
Publisher: MDPI AG
Date: 20-08-2021
DOI: 10.3390/BIOMEDICINES9081061
Abstract: Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.
Publisher: MDPI AG
Date: 17-05-2021
DOI: 10.3390/DIAGNOSTICS11050887
Abstract: Machine learning (ML) algorithms are widely used to develop predictive frameworks. Accurate prediction of Alzheimer’s disease (AD) age of onset (ADAOO) is crucial to investigate potential treatments, follow-up, and therapeutic interventions. Although genetic and non-genetic factors affecting ADAOO were elucidated by other research groups and ours, the comprehensive and sequential application of ML to provide an exact estimation of the actual ADAOO, instead of a high-confidence-interval ADAOO that may fall, remains to be explored. Here, we assessed the performance of ML algorithms for predicting ADAOO using two AD cohorts with early-onset familial AD and with late-onset sporadic AD, combining genetic and demographic variables. Performance of ML algorithms was assessed using the root mean squared error (RMSE), the R-squared (R2), and the mean absolute error (MAE) with a 10-fold cross-validation procedure. For predicting ADAOO in familial AD, boosting-based ML algorithms performed the best. In the sporadic cohort, boosting-based ML algorithms performed best in the training data set, while regularization methods best performed for unseen data. ML algorithms represent a feasible alternative to accurately predict ADAOO with little human intervention. Future studies may include predicting the speed of cognitive decline in our cohorts using ML.
Publisher: SAGE Publications
Date: 28-03-2018
Abstract: Objective: The aim of this study is to contrast the genetics of neuropsychological tasks in in iduals from nuclear families clustering ADHD in a Caribbean community. Method: We recruited and clinically characterized 408 in iduals using an extensive battery of neuropsychological tasks. The genetic variance underpinning these tasks was estimated by heritability. A predictive framework for ADHD diagnosis was derived using these tasks. Results: We found that in iduals with ADHD differed from controls in tasks of mental control, visuospatial ability, visuoverbal memory, phonological and verbal fluency, verbal and semantic fluency, cognitive flexibility, and cognitive ability. Among them, tasks of mental control, visuoverbal memory, phonological fluency, semantic verbal fluency, and intelligence had a significant heritability. A predictive model of ADHD diagnosis using these endophenotypes yields remarkable classification rate, sensitivity, specificity, and precision values (above 80%). Conclusion: We have dissected new cognitive endophenotypes in ADHD that can be suitable to assess the neurobiological and genetic basis of ADHD.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2019
DOI: 10.1007/S12035-019-01798-0
Abstract: Alzheimer’s disease (AD) is progressive brain disorder that affects ~ 50 million people worldwide and has no current effective treatment. AD age of onset (ADAOO) has shown to be critical for the identification of genes that modify the appearance of AD signs and symptoms in a specific population. We clinically characterized and whole-exome genotyped 71 in iduals with AD from the Paisa genetic isolate, segregating the ( PSEN1 ) E280A dominant fully penetrant mutation, and analyzed the potential recessive effects of ~ 50,000 common functional genomic variants to the ADAOO. Standard quality control and filtering procedures were applied, and recessive single- and multi-locus linear mixed-effects models were used. We identified genetic variants in the SLC9C1 , CSN1S1 , and LOXL4 acting recessively to delay ADAOO up to ~ 11, ~ 6, and ~ 9 years on average, respectively. In contrast, the CC recessive genotype in marker DHRS4L2 -rs2273946 accelerates ADAOO by ~ 8 years. This study, reports new recessive variants modifying ADAOO in PSEN1 E280A mutation carriers. This set of genes are implicated in important biological processes and molecular functions commonly affected by genes associated with the etiology of AD such as APP , APOE , and CLU . Future functional studies using modern techniques such as induced pluripotent stem cells will allow a better understanding of the over expression and down regulation of these recessive modifier variants and hence the pathogenesis of AD. These results are important for prediction of AD and ultimately, substantial to develop new therapeutic strategies for in iduals at risk or affected by AD.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2020
DOI: 10.1038/S41398-020-00881-8
Abstract: Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75–80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) s le, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa s le, 298 subjects) and 3 (US s le, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes ( GALC , CERS6 , SMPD1 , SMPDL3B , CERS2 , FADS3 , ELOVL5 , and CERK ). Successful local replication for associations with variants in GALC , SMPD1 , and CERS6 was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increased GALC expression in the cerebellum.
Publisher: Universidad Nacional de Colombia
Date: 18-01-2016
Abstract: We propose and illustrate a new graphical method to perform diagnostic analyses in two-way contingency tables. In this method, one observation is added or removed from each cell at a time, whilst the other cells are held constant, and the change in a test statistic of interest is graphically represented. The method provides a very simple way of determining how robust our model is (and hence our conclusions) to small changes introduced to the data. We illustrate via four ex les, three of them from real-world applications, how this method works.
Publisher: Wiley
Date: 16-11-2012
DOI: 10.1111/DMCN.12038
Abstract: Aim Difficulties in neurocognition and social interaction are the most prominent causes of morbidity and long‐term disability in children with neurofibromatosis type 1 (NF1). Symptoms of attention‐deficit–hyperactivity disorder (ADHD) have also been extensively recognized in NF1. However, systematic evaluation of symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited. Method We present a retrospective, cross‐sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD. Results Sixty‐six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5y 4mo). Forty percent of our NF1 s le had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T ≥ 60), and 14% reached levels consistent with those seen in children with ASDs (T ≥ 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral disorders. There was a statistically significant relationship between symptoms of ADHD and ASD (χ 2 =9.11, df=1, p =0.003, φ=0.56). Particularly salient were the relationships between attention and hyperactivity deficits, with impairments in social awareness and social motivation. Interpretation We found that symptoms of ASD in our NF1 population were raised, consistent with previous reports. Further characterization of the specific ASD symptoms and their impact on daily function is fundamental to the development and implementation of effective interventions in this population, which will probably include a combination of medical and behavioral approaches.
Publisher: Springer Science and Business Media LLC
Date: 25-10-2017
DOI: 10.1038/MP.2016.174
Publisher: Springer Science and Business Media LLC
Date: 04-03-2017
Publisher: Wiley
Date: 14-02-2022
DOI: 10.1002/QRE.3086
Abstract: This paper aims to design a variable parameters synthetic control chart for first‐order AR(1) autocorrelated data following a Gaussian process. To improve the statistical performance in detecting small changes and maintaining a low false alarm rate, the variable parameters control chart was combined with the Conforming Run Length (CRL) sub‐chart to determine when to implement tight or relaxed control and intervene to identify an assignable cause. The statistical design of the proposed chart was performed under a discrete‐time Markov chain approach and a non‐linear programming mathematical model to obtain, using a genetic algorithm (GA), the values of the design parameters that minimise the average time to signal the out‐of‐control state (). A sensitivity analysis was performed to examine the behaviour of the in the face on changes in the parameters. Also, a performance evaluation was conducted to compare the proposed chart with other adaptive synthetic charts, the synthetic control chart and the chart developed by Costa and Machado. Our results indicate that this proposal is faster to detect small changes in the process mean considering the autocorrelation of the data.
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.YGYNO.2009.06.039
Abstract: To compare the surgical outcome of robotic radical hysterectomy (RRH) versus abdominal radical hysterectomy (ARH) for the treatment of early stage cervical cancer. A prospective collection of data of all RRH for stages IA2-IIA cervical cancer was done. The procedures were performed at the European Institute of Oncology, Milan, Italy, between November 1, 2006 and February 1, 2009. A total of 40 RRH were analyzed, and compared with 40 historic ARH cases. The groups did not differ significantly in body mass index, stage, histology, or intraoperative complications, but in age (p=0.035). The mean (SD) operative time was significantly shorter for ARH than RRH, 199.6 (65.6) minutes and 272.27 (42.3) minutes respectively (p=0.0001). The mean (SD) estimated blood loss (EBL) was 78 ml (94.8) in RRH group and 221.8 ml (132.4) in ARH. This difference was statistically significant in favor of RRH group (p<0.0001). Statistically significantly higher number of pelvic lymph nodes was removed by ARH than by RRH, mean (SD) 26.2 (11.7) versus 20.4 (6.9), p<0.05. Mean length of stay was significantly shorter for the RRH group (3.7 versus 5.0 days, p<0.01). There was no significant difference in terms of postoperative complications between groups. This study shows that RRH is safe and feasible. However, a comparison of oncologic outcomes and cost-benefit analysis is still needed and it has to be carefully evaluated in the future.
Publisher: Public Library of Science (PLoS)
Date: 03-06-2020
Publisher: Springer Science and Business Media LLC
Date: 12-2016
DOI: 10.1038/MP.2015.177
Publisher: Springer Science and Business Media LLC
Date: 09-07-2021
DOI: 10.1186/S13040-021-00266-7
Abstract: High-throughput sequencing enables the analysis of the composition of numerous biological systems, such as microbial communities. The identification of dependencies within these systems requires the analysis and assimilation of the underlying interaction patterns between all the variables that make up that system. However, this task poses a challenge when considering the compositional nature of the data coming from DNA-sequencing experiments because traditional interaction metrics (e.g., correlation) produce unreliable results when analyzing relative fractions instead of absolute abundances. The compositionality-associated challenges extend to the classification task, as it usually involves the characterization of the interactions between the principal descriptive variables of the datasets. The classification of new s les atients into binary categories corresponding to dissimilar biological settings or phenotypes (e.g., control and cases) could help researchers in the development of treatments/drugs. Here, we develop and exemplify a new approach, applicable to compositional data, for the classification of new s les into two groups with different biological settings. We propose a new metric to characterize and quantify the overall correlation structure deviation between these groups and a technique for dimensionality reduction to facilitate graphical representation. We conduct simulation experiments with synthetic data to assess the proposed method’s classification accuracy. Moreover, we illustrate the performance of the proposed approach using Operational Taxonomic Unit (OTU) count tables obtained through 16S rRNA gene sequencing data from two microbiota experiments. Also, compare our method’s performance with that of two state-of-the-art methods. Simulation experiments show that our method achieves a classification accuracy equal to or greater than 98% when using synthetic data. Finally, our method outperforms the other classification methods with real datasets from gene sequencing experiments.
Publisher: Springer Science and Business Media LLC
Date: 02-06-2015
Publisher: Springer Science and Business Media LLC
Date: 16-02-2010
DOI: 10.1038/MP.2010.6
Abstract: Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five s les from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide s les (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.
Publisher: Springer Science and Business Media LLC
Date: 09-06-2010
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000328203
Abstract: Holoprosencephaly (HPE), which results from failed or incomplete midline forebrain ision early in gestation, is the most common forebrain malformation. The etiology of HPE is complex and multifactorial. To date, at least 12 HPE-associated genes have been identified, including i TGIF /i (transforming growth factor beta-induced factor), located on chromosome 18p11.3. i TGIF /i encodes a transcriptional repressor of retinoid responses involved in TGF-β signaling regulation, including Nodal signaling. i TGIF /i mutations are reported in approximately 1–2% of patients with non-syndromic, non-chromosomal HPE.We combined data from our comprehensive studies of HPE with a literature search for all in iduals with HPE and evidence of mutations affecting i TGIF /i in order to establish the genotypic and phenotypic range. We describe 2 groups of patients: 34 with intragenic mutations and 21 with deletions of i TGIF /i . These in iduals, which were ascertained from our research group, in collaboration with other centers, and through a literature search, include 38 probands and 17 mutation-positive relatives. The majority of intragenic mutations occur in the TGIF homeodomain. Patients with mutations affecting i TGIF /i recapitulate the entire phenotypic spectrum observed in non-chromosomal, non-syndromic HPE. We identified a statistically significant difference between the 2 groups with respect to inheritance, as i TGIF /i deletions were more likely to be de novo in comparison to i TGIF /i mutations (χ sup /sup sub (2) /sub = 6.97, p sub ermutated /sub = 0.0356). In addition, patients with i TGIF /i deletions were also found to more commonly present with manifestations beyond the craniofacial and neuroanatomical features associated with HPE (p = 0.0030). These findings highlight differences in patients with intragenic mutations versus deletions affecting i TGIF /i , and draw attention to the homeodomain region, which appears to be particularly relevant to HPE. These results may be useful for genetic counseling of affected patients.
Publisher: MDPI AG
Date: 15-09-2021
Abstract: Temporal processing (TP) is associated with functions such as perception, verbal skills, temporal perspective, and future planning, and is intercorrelated with working memory, attention, and inhibitory control, which are highly impaired in in iduals with attention deficit hyperactivity disorder (ADHD). Here we evaluate TP measures as potential endophenotypes in Caribbean families ascertained from probands affected by ADHD. A total of 232 in iduals were recruited and clinically evaluated using an extensive battery of neuropsychological tasks and reaction time (RT)-based task paradigms. Further, the heritability (genetic variance underpinning phenotype) was estimated as a measure of the genetics apportionment. A predictive framework for ADHD diagnosis was derived using these tasks. We found that in iduals with ADHD differed from controls in neuropsychological tasks assessing mental control, visual-verbal memory, verbal fluency, verbal, and semantic fluency. In addition, TP measures such as RT, errors, and variability were also affected in in iduals with ADHD. Moreover, we determined that only omission and commission errors had significant heritability. In conclusion, we have disentangled omission and commission errors as possible TP endophenotypes in ADHD, which can be suitable to assess the neurobiological and genetic basis of ADHD. A predictive model using these endophenotypes led to remarkable sensitivity, specificity, precision and classification rate for ADHD diagnosis, and may be a useful tool for patients’ diagnosis, follow-up, and longitudinal assessment in the clinical setting.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: MDPI AG
Date: 26-06-2021
Abstract: Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected in iduals. ADHD-affected patients display visual–motor and visuospatial abilities and skills that depart from those exhibited by non-affected in iduals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic ersity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically erse community with a vast African American contribution, where ADHD studies are scarce.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2018
DOI: 10.1038/S41598-018-22629-7
Abstract: HIV infection has a tremendous impact on the immune system’s proper functioning. The mucosa-associated lymphoid tissue (MALT) is significantly disarrayed during HIV infection. Compositional changes in the gut microbiota might contribute to the mucosal barrier disruption, and consequently to microbial translocation. We performed an observational, cross-sectional study aimed at evaluating changes in the fecal microbiota of HIV-infected in iduals from Colombia. We analyzed the fecal microbiota of 37 in iduals via 16S rRNA gene sequencing 25 HIV-infected patients and 12 control (non-infected) in iduals, which were similar in body mass index, age, gender balance and socioeconomic status. To the best of our knowledge, no such studies have been conducted in Latin American countries. Given its compositional nature, microbiota data were normalized and transformed using Aitchison’s Centered Log-Ratio. Overall, a change in the network structure in HIV-infected patients was revealed by using the SPIEC-EASI MB tool. Genera such as Blautia , Dorea , Yersinia , Escherichia-Shigella complex, Staphylococcus , and Bacteroides were highly relevant in HIV-infected in iduals. Differential abundance analysis by both sparse Partial Least Square-Discriminant Analysis and Random Forest identified a greater abundance of Lachnospiraceae-OTU69, Blautia , Dorea , Roseburia , and Erysipelotrichaceae in HIV-infected in iduals. We show here, for the first time, a predominantly Lachnospiraceae-based signature in HIV-infected in iduals.
Publisher: Colegio Oficial de Psicologos de Madrid
Date: 2018
DOI: 10.5093/PI2018A1
Publisher: MDPI AG
Date: 20-05-2022
DOI: 10.20944/PREPRINTS202205.0280.V1
Abstract: A whole-exome capture and next-generation sequencing applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, severe cognitive deficit, without any identifiable Syndromic pattern, and to her parents, disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated to Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated one, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURA WT and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural confor-mation in the ~5& Aring surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA Docking corroborated these results in silico Analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, i) the energetic and stereochemical, ii) the hydropathic indices and polarity surfaces, and iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate at the atomic resolution the specific surrounding region affected by these mutations and paves the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.
Publisher: Hindawi Limited
Date: 10-2009
DOI: 10.1002/HUMU.21090
Publisher: SAGE Publications
Date: 19-05-2022
DOI: 10.1177/10870547211015426
Abstract: To investigate whether single nucleotide polymorphisms (SNPs) in the ADGRL3, DRD4, and SNAP25 genes are associated with and predict ADHD severity in families from a Caribbean community. ADHD severity was derived using latent class cluster analysis of DSM-IV symptomatology. Family-based association tests were conducted to detect associations between SNPs and ADHD severity latent phenotypes. Machine learning algorithms were used to build predictive models of ADHD severity based on demographic and genetic data. In iduals with ADHD exhibited two seemingly independent latent class severity configurations. SNPs harbored in DRD4, SNAP25, and ADGRL3 showed evidence of linkage and association to symptoms severity and a potential pleiotropic effect on distinct domains of ADHD severity. Predictive models discriminate severe from non-severe ADHD in specific symptom domains. This study supports the role of DRD4, SNAP25, and ADGRL3 genes in outlining ADHD severity, and a new prediction framework with potential clinical use.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JAUT.2016.05.003
Abstract: Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. DNA of 47 in iduals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2012
DOI: 10.1007/S00520-012-1571-Z
Abstract: The primary purpose of this study is to evaluate health-related quality of life (HR-QOL) of gynecologic cancer patients undergoing laparotomy. Women who underwent laparotomy by gynecologic cancer completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of life questionnaires (QLQ-C30 and QLQ-OV28) presurgery and at 1 month. Of the 181 women studied between January 2007 and March 2008, 116 women (64.1%) had ovarian cancer, 27 (14.9%) had cervical cancer, and 29 (16.0%) had endometrial cancer. By 1 month post-surgery, there was a significant decrease in HR-QOL on the global, abdominal/gastrointestinal (GI) score, body image, chemotherapy side effects, and other single items of the OV28 questionnaire, as well as on physical, role and social functioning, fatigue, nausea and vomiting, pain, insomnia, constipation, appetite loss, and financial difficulties items on C30 questionnaires. Emotional functioning on C30 questionnaires was significantly improved 1 month after surgery. The majority of these items persisted 1 month after surgery only in patients with ovarian cancer. Abdominal/GI score on OV28 questionnaires as well as role and physical functioning on C30 questionnaires were significantly lower between baseline and postsurgical HR-QOL in women with other gynecologic malignancies. The results suggest a significant impact of HR-QOL among gynecologic cancer patients 1 month after laparotomy, particularly among those with ovarian cancer.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2011
Publisher: BMJ
Date: 02-04-2009
Publisher: MDPI AG
Date: 30-06-2022
Abstract: A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA–Phe233del showed that the occurrence of the Phe233del affects between 220–320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein–DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA–Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics–Molecular Mechanics (QM–MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.
Publisher: Elsevier BV
Date: 10-2009
Publisher: Universidad de San Buenaventura
Date: 30-04-2021
Abstract: Since its beginnings, Psychology has been prone to both data generation and understanding of human behavior through data analysis. Back in 1879, Dr. Wilheim Wundt opened the first experimental psychology lab at the University of Leipzig to study reaction times. To many, this is considered the start of Psychology as a separate scientific discipline and the use of data analysis for data-driven decision making in the field (Flis, 2019 Tweney, 2003). In this Editorial, we briefly discuss how Psychology students, clinicians, and researchers may take part of the data revolution and help transforming Psychology, as we know it, into Machine Learning Psychology.
Publisher: Universidad Nacional de Colombia
Date: 14-07-2016
Abstract: De acuerdo con la estilística y crítica literaria la obra Cien Años de Soledad, escrita por Gabriel García Márquez, se caracteriza por una alusión constante a los personajes de la historia y un narrador que usa un tono neutro para relatar los eventos. En este artículo se utilizan métodos estilométricos para ratificar tales afirmaciones y proveer nuevos resultados acerca de esta novela. Los hallazgos indican que el autor hace uso de palabras abstractas y palabras referentes a objetos con los que se puede interactuar físicamente para producir el efecto lingüístico característico del realismo mágico. Dada la importancia de los resultados a partir de métodos estilométricos, se plantean algunas ideas acerca de las implicaciones que esta metodología puede tener en áreas de la psicolingüística y de la psicología cognitiva.
Publisher: Springer Science and Business Media LLC
Date: 25-02-2017
DOI: 10.1007/S12402-017-0223-Z
Abstract: Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.
Publisher: Wiley
Date: 30-08-2016
DOI: 10.1002/AJMG.B.32493
Abstract: The identification of mutations modifying the age of onset (AOO) in Alzheimer's disease (AD) is crucial for understanding the natural history of AD and, therefore, for early interventions. Patients with sporadic AD (sAD) from a genetic isolate in the extremes of the AOO distribution were whole-exome genotyped. Single- and multi-locus linear mixed-effects models were used to identify functional variants modifying AOO. A posteriori enrichment and bioinformatic analyses were applied to evaluate the non-random clustering of the associate variants to physiopathological pathways involved in AD. We identified more than 20 pathogenic, genome-wide statistically significant mutations of major modifier effect on the AOO. These variants are harbored in genes implicated in neuron apoptosis, neurogenesis, inflammatory processes linked to AD, oligodendrocyte differentiation, and memory processes. This set of new genes harboring these mutations could be of importance for prediction, follow-up and eventually as therapeutical targets of AD. © 2016 Wiley Periodicals, Inc.
Publisher: Wiley
Date: 10-2010
DOI: 10.1016/J.IJGO.2010.05.006
Abstract: To evaluate the feasibility of laparoscopic management of women with gynecologic emergencies by the residents and the chief resident in an organized resident training program. A retrospective study of patients with gynecologic emergencies who underwent laparoscopic surgery between January 1, 1999, and May 31, 2006 was done. For the 369 patients included, the mean operative time of 74±31.35 minutes was significantly increased by advanced patient age (P<0.001), pelvic inflammatory disease with or without tubo-ovarian abscess (PID±TOA) (P<0.050), the first semester of chief residency (P<0.050), and conversion to laparotomy (P<0.001). Mean length of hospital stay was 40±24 hours. Factors such as advanced patient age (P<0.001), prolonged length of surgery (P<0.001), PID±TOA (P<0.001), first semester of chief residency (P<0.050), conversion to laparotomy (P<0.001), and blood transfusion (P<0.050) significantly increased the length of hospital stay. The conversion rate to laparotomy was 4.6% (n=17), and it was significantly associated with advanced women age (OR 1.11 95% CI, 1.05-1.17, P<0.001) and PID±TOA (OR 6.04 95%CI, 2.17-16.62, P<0.001). Postoperative complications were recorded in 3 (0.81%) patients. Laparoscopic management of gynecologic emergencies by senior residents and a chief resident within an organized resident training program is feasible. These results reinforce the relevance of a well-structured residency endoscopic training program.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2011
DOI: 10.1038/MP.2011.59
Publisher: MDPI AG
Date: 25-01-2020
Abstract: Presented here are five members of a family that was ascertained from an isolated, consanguineous, indigenous Amerindian community in Colombia that was affected with calpain 3-related, limb-girdle muscular dystrophy type R1. These patients are homozygous for a unique and novel deletion of four bases (TGCC) in exon 3 of the calpain 3 gene (CAPN3) (NM_000070.2 NP_000061.1) (g.409_412del). The mutation site occurs at the CysPc protein domain, triggering a modified truncated protein structure and affecting motifs within the calpain-like thiol protease family (peptidase family C2) region. The patients reported here developed a very severe phenotype with primary contractures, spinal rigidity in the early stages of the disease, and bilateral talipes equinovarus (clubfoot) in the most affected patients who had the selective involvement of their extremities’ distal muscles in a way that resembled Emery–Dreifuss syndrome. We recommend mandatory screening for calpainopathy in all patients with an Emery–Dreifuss-like syndrome or those presenting a non-congenital illness with primary contractures and who, because of other data, are suspected of having muscular dystrophy.
Publisher: Springer Science and Business Media LLC
Date: 20-07-2012
Publisher: Wiley
Date: 15-02-2010
DOI: 10.1002/AJMG.C.30240
Publisher: MDPI AG
Date: 25-11-2020
DOI: 10.3390/EN13236189
Abstract: Modern power systems must provide efficient, reliable, and environmentally responsible energy. Recently, the inclusion of Microgrids (MGs) has allowed us to overcome some difficulties and face important challenges in this direction, especially related to the use of alternative energy sources. Increased and probabilistic demand, as well as limited energy supply, pose the need to evaluate the reliability of any distribution system (DS) when MGs are introduced. Here we reviewed and classified the state-of-the-art of reliability assessment (RA) in MGs. Initially, we contextualize RA in distribution systems. Next, each of the MGs subsystems components are introduced and the questions (1) why is it important to evaluate the reliability in Microgrids? (2) how do Microgrids influence the reliability of distribution systems? and (3) how does each of its subsystems influence the reliability of the Microgrids? are addressed. A total of 1395 research studies were published between 2002 and 2020. Using the PRISMA model, 147 met the inclusion criteria (71% correspond to research papers and 29% to reviews 62% were published in journals, 34% were conference papers and 4% were books). The first study dates from 1971. Despite immense advances in MGs, we identified that (1) real test systems constitute an emerging trend (2) although new MG configurations sound promising, the development and application of new RA techniques are a necessary step towards the identification of potential pitfalls of such architectures (3) new RA methods or variations of the existing ones, whether analytical or simulation-based, are constantly being proposed, but their comparison for a particular DS, including MGs, are yet to be performed and (4) more research studies are needed to assess how new control strategies and information and communications technology impact MGs reliability. Future lines of research could build upon these gaps to enhance reliability, especially when alternative energy resources are available.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2017
DOI: 10.1038/S41598-017-10640-3
Abstract: Plant litter represents a major basal resource in streams, where its decomposition is partly regulated by litter traits. Litter-trait variation may determine the latitudinal gradient in decomposition in streams, which is mainly microbial in the tropics and detritivore-mediated at high latitudes. However, this hypothesis remains untested, as we lack information on large-scale trait variation for riparian litter. Variation cannot easily be inferred from existing leaf-trait databases, since nutrient resorption can cause traits of litter and green leaves to erge. Here we present the first global-scale assessment of riparian litter quality by determining latitudinal variation (spanning 107°) in litter traits (nutrient concentrations physical and chemical defences) of 151 species from 24 regions and their relationships with environmental factors and phylogeny. We hypothesized that litter quality would increase with latitude (despite variation within regions) and traits would be correlated to produce ‘syndromes’ resulting from phylogeny and environmental variation. We found lower litter quality and higher nitrogen:phosphorus ratios in the tropics. Traits were linked but showed no phylogenetic signal, suggesting that syndromes were environmentally determined. Poorer litter quality and greater phosphorus limitation towards the equator may restrict detritivore-mediated decomposition, contributing to the predominance of microbial decomposers in tropical streams.
Publisher: Informa UK Limited
Date: 15-05-2020
Publisher: Hindawi Limited
Date: 08-07-2022
DOI: 10.1155/2022/7239464
Abstract: In this systematic literature review (SLR), we use a series of quantitative bibliometric analyses to (1) identify the main papers, journals, and authors of the publications that make use of statistical analysis (SA) and machine learning (ML) tools as well as technological elements of smart cities (TESC) and Geographic Information Systems to predict road traffic accidents (RTAs) (2) determine the extent to which the identified methods are used for the analysis of RTAs and current trends regarding their use (3) establish the relationship between the set of variables analyzed and the frequency and severity of RTAs and (4) identify gaps in method use to highlight potential areas for future research. A total of 3888 papers published between January 2000 and June 2021, distributed in four clusters—RTA + HA + SA (SA, n = 399) RTA + HA + ML (ML, n = 858) RTA + HA + SC (TESC, n = 2327) and RTA + HA + GIS (GIS, n = 304)—were analyzed. We identified Accident Analysis and Prevention as the most important journal, Fred Mannering as the main author, and The Statistical Analysis of Crash-Frequency Data: A Review and Assessment of Methodological Alternatives as the most cited publication. Although the negative binomial regression method was used for several years, we noticed that other regression models as well as methods based on deep learning, convolutional neural networks, transfer learning, 5G technology, Internet of Things, and intelligent transport systems have recently emerged as suitable alternatives for RTA analysis. By introducing a new approach based on computational algorithms and data visualization, this SLR fills a gap in the area of RTA analysis and provides a clear picture of the current scientific production in the field. This information is crucial for projecting further research on RTA analysis and developing computational and data visualization tools oriented to the automation of RTA predictions based on intelligent systems.
Publisher: Wiley
Date: 03-08-2010
DOI: 10.1002/AJMG.A.33572
Publisher: Oxford University Press (OUP)
Date: 12-09-2008
DOI: 10.1093/HMG/DDN294
Publisher: Springer Science and Business Media LLC
Date: 23-09-2022
DOI: 10.1038/S41598-022-20343-Z
Abstract: Attention deficit/hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder. Single nucleotide polymorphisms (SNPs) in the Adhesion G Protein-Coupled Receptor L3 ( ADGRL3 ) gene are associated with increased susceptibility to developing ADHD worldwide. However, the effect of ADGRL3 non-synonymous SNPs (nsSNPs) on the ADGRL3 protein function is vastly unknown. Using several bioinformatics tools to evaluate the impact of mutations, we found that nsSNPs rs35106420, rs61747658, and rs734644, previously reported to be associated and in linkage with ADHD in disparate populations from the world over, are predicted as pathogenic variants. Docking analysis of rs35106420, harbored in the ADGLR3- hormone receptor domain (HRM, a common extracellular domain of the secretin-like GPCRs family), showed that HRM interacts with the Glucose-dependent insulinotropic polypeptide (GIP), part of the incretin hormones family. GIP has been linked to the pathogenesis of diabetes mellitus, and our analyses suggest a potential link to ADHD. Overall, the comprehensive application of bioinformatics tools showed that functional mutations in the ADGLR3 gene disrupt the standard and wild ADGRL3 structure, most likely affecting its metabolic regulation. Further in vitro experiments are granted to evaluate these in silico predictions of the ADGRL3-GIP interaction and dissect the complexity underlying the development of ADHD.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2016
DOI: 10.1007/S12402-016-0202-9
Abstract: The Wender-Utah Rating Scale (WURS) is a widely used self-report instrument for retrospective assessment of childhood ADHD. However, many WURS items are not specific to ADHD. Here, we investigated the effect of excluding these items on the performance of the WURS in predicting adult ADHD based on previous diagnosis and current clinically significant symptoms. The study was conducted on a s le of adults (n = 1014 48 % male) participating in a family-based investigation of ADHD. Participants completed the 61-item WURS questionnaire and the 66-item Conners Adult ADHD Rating Scale. Receiver operating characteristic (ROC) curves were used to compare the performance of the eight-item WURS (WURS-8) and the longer WURS-25 in predicting previous ADHD diagnosis and current clinically significant ADHD symptoms. WURS-8 and WURS-25 have approximately the same power to predict adult ADHD, based on either previous diagnosis or current symptoms (area under the ROC curves >0.8). WURS-8 performs at least as well as the longer WURS-25 in predicting adult ADHD. This 8-item questionnaire is thus a valid instrument and is especially useful for screening for ADHD in large epidemiological s les.
Publisher: Informa UK Limited
Date: 28-06-2018
DOI: 10.1080/02699931.2017.1344121
Abstract: The valence-space metaphor research area investigates the metaphorical mapping of valenced concepts onto space. Research findings from this area indicate that positive, neutral, and negative concepts are associated with upward, midward, and downward locations, respectively, in the vertical plane. The same research area has also indicated that such concepts seem to have no preferential location on the horizontal plane. The approach-avoidance effect consists in decreasing the distance between positive stimuli and the body (i.e. approach) and increasing the distance between negative stimuli and the body (i.e. avoid). Thus, the valence-space metaphor accounts for the mapping of valenced concepts onto the vertical and horizontal planes, and the approach-avoidance effect accounts for the mapping of valenced concepts onto the "depth" plane. By using a cube conceived for the study of allocation of valenced concepts onto 3D space, we show in three studies that positive concepts are placed in upward locations and near the participants' body, negative concepts are placed in downward locations and far from the participants' body, and neutral concepts are placed in between these concepts in both planes.
Publisher: MDPI AG
Date: 04-08-2021
Abstract: Human Immunodeficiency Virus type 1 (HIV-1) infection is a chronic disease that affects ~40 million people worldwide. HIV-associated neurocognitive disorders (HAND) are common in in iduals with HIV-1 Infection, and represent a recent public health problem. Here we evaluate the performance of a recently proposed short protocol for detecting HAND by studying 60 in iduals with HIV-1-Infection and 60 seronegative controls from a Caribbean community in Barranquilla, Colombia. The short evaluation protocol used significant neuropsychological tests from a previous study of asymptomatic HIV-1 infected patients and a group of seronegative controls. Brief screening instruments, i.e., the Mini-mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS), were also applied. Using machine-learning techniques, we derived predictive models of HAND status, and evaluated their performance with the ROC curves. The proposed short protocol performs exceptionally well yielding sensitivity, specificity, and overall prediction values %, and better predictive capacity than that of the MMSE and IHDS. Community-specific cut-off values for HAND diagnosis, based on the MMSE and IHDS, make this protocol suitable for HAND screening in in iduals from this Caribbean community. This study shows the effectivity of a recently proposed short protocol to detect HAND in in iduals with asymptomatic HIV-1-Infection. The application of community-specific cut-off values for HAND diagnosis in the clinical setting may improve HAND screening accuracy and facilitate patients’ treatment and follow-up. Further studies are needed to assess the performance of this protocol in other Latin American populations.
Publisher: Informa UK Limited
Date: 07-02-2018
DOI: 10.1080/09540121.2018.1428728
Abstract: Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a s le consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36.07 years. A protocol of neuropsychological and psychopathological tests was applied to the participants. The group of patients with asymptomatic HIV infections significantly underperformed on tasks that assessed global cognitive screening, attention span, learning, phonemic verbal fluency, auditory-verbal comprehension, information processing speed, cognitive flexibility, and motor skills compared to the group of seronegative participants. No significant differences were found in memory, visual confrontation naming, vocabulary, inhibition, and instrumental activities of daily living. Additionally, the patients with asymptomatic HIV-1 infection had a higher anxiety index than the seronegative participants, but no significant difference was found in depression. A correlation was found between depression and anxiety. In conclusion, the patients with asymptomatic HIV-1 infection had lower cognitive performances than the seronegative participants in the cognitive functions mentioned above and more anxiety but still performed the instrumental activities of daily living.
Publisher: MDPI AG
Date: 16-08-2019
DOI: 10.3390/CELLS8080907
Abstract: Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 in iduals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele p = 2.46 × 10−4), rs2282794-FGF1 (A allele p = 1.33 × 10−2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10−2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.
Publisher: Elsevier BV
Date: 04-2012
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/9760314
Abstract: We previously reported age of onset (AOO) modifier genes in the world’s largest pedigree segregating early-onset Alzheimer’s disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty in iduals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 ( DAOA ) gene (rs2391191, P = 1.94 × 10 −4 , P FDR = 9.34 × 10 −3 ) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10 −3 , P FDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, P FDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 ( DAOA ) gene could be pivotal for understanding the genetic basis of AD.
Publisher: Elsevier BV
Date: 10-2012
Location: United States of America
No related grants have been discovered for Jorge Vélez.