RESUMEN
Background & objectives: ADAM33 is implicated as a potentially strong candidate gene for asthma and bronchial hyper-responsiveness. Many polymorphisms of ADAM33 have been studied along with ADAM33 expression in various cells of the lungs. Haplotype analysis also showed association with asthma in different populations across the world. Therefore, the aim of this study was to perform a comprehensive screening of ADAM33 polymorphisms in adult patients with asthma. Methods: Thirty five polymorphisms of ADAM33 were genotyped in 55 patients with asthma and 53 controls. The association of single nucleotide polymorphisms (SNPs) and haplotypes with phenotypes of asthma was analysed. Results: The genotype, minor allele frequency, odds ratio and Hardy-Weinberg equilibrium did not show any significant difference among cases and controls. No association was found between SNPs of ADAM33 with the severity of asthma. Correlation analysis of ADAM33 SNPs to the phenotypes, based on clinical variables and allergen sensitization, did not show significant difference. Haplotype analysis showed that rs2280090 and rs2280091 were associated with asthma in the patient group. Interpretation & conclusions: Haplotype analysis showed an association of the two SNP variations with asthma. These SNPs lead to amino acid change and are prone to phosphorylation, which may affect expression levels and protein function of ADAM33 and asthma susceptibility.
Asunto(s)
Proteínas ADAM/genética , Asma/genética , Haplotipos , Adulto , Alelos , Bronquios/patología , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Proyectos Piloto , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND & OBJECTIVES: Aneuploids are the most common chromosomal abnormality in liveborns and are usually the result of non-disjunction (NDJ) in meiosis. Copy number variations (CNVs) are large structural variations affecting the human genome. CNVs influence critical genes involved in causing NDJ by altering their copy number which affects the clinical outcome. In this study influence of CNVs on critical meiotic recombination was examined using new computational technologies to assess their role in causing aneuploidy. METHODS: This investigation was based on the analysis of 12 random normal populations consisting of 1714 individuals for aneuploid causing genes under CNV effect. To examine the effect of CNVs on genes causing aneuploidy, meiotic recombination genes were analyzed using EnrichR, WebGestalt and Ingenuity Pathway Analysis (IPA). RESULTS: Forty three NDJ genes were found under CNV burden; IPA (Ingenuity Pathway Analysis) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of CNV in meiotic recombination genes revealed a significant role of breast cancer gene 1, amyloid protein precursor, mitogen-activated protein kinase and nerve growth factor as key molecular players involved in causing aneuploidy. Interaction between these genes with other CNV-overlapping genes involved in cell cycle, recombination and meiosis might lead to increased incidences of aneuploidy. INTERPRETATION & CONCLUSIONS: The findings of this study implied that the effect of CNVs on normal genome contributed in amplifying the occurrences of chromosomal aneuploidies. The normal individuals consisting of variations in the susceptible genes causing aneuploids in the population remain undetected until the disorder genes express in the succeeding generations.
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Biomarcadores , Variaciones en el Número de Copia de ADN/genética , Meiosis/genética , Recombinación Genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Femenino , Genoma Humano , Humanos , India , Masculino , Persona de Mediana EdadRESUMEN
RAN tests were administered to 600 typically developing children, 60 each from grade level one through grade ten (30 boys and 30 girls), who learn two distinct languages, English and Kannada simultaneously from the very first grade. The overall results were in accordance with similar previous studies in English and other European languages. The developmental trajectories were similar across the languages to a large extent; but the results also showed some differences across languages with respect to synchrony between the measures and the overall naming speed. Though some of the differences could be ascribed to the bilingual/biliterate culture and language use, there are enough scopes for future researches to examine these issues.
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Pruebas del Lenguaje , Multilingüismo , Lectura , Adolescente , Niño , Desarrollo Infantil , Femenino , Humanos , Lenguaje , Aprendizaje , Masculino , Tiempo de ReacciónRESUMEN
Global patterns of copy number variations (CNVs) in chromosomes are required to understand the dynamics of genome organization and complexity. For this study, analysis was performed using the Affymetrix Genome-Wide Human SNP Array 6.0 chip and CytoScan High-Density arrays. We identified a total of 44 109 CNVs from 1715 genomes with a mean of 25 CNVs in an individual, which established the first drafts of population-specific CNV maps providing a rationale for prioritizing chromosomal regions. About 19 905 ancient CNVs were identified across all chromosomes and populations at varying frequencies. CNV count, and sometimes CNV size, contributed to the bulk CNV size of the chromosome. Population specific lengthening and shortening of chromosomal length was observed. Sex bias for CNV presence was largely dependent on ethnicity. Lower CNV inheritance rate was observed for India, compared to YRI and CEU. A total of 33 candidate CNV hotspots from 5382 copy number (CN) variable region (CNVR) clusters were identified. Population specific CNV distribution patterns in p and q arms disturbed the assumption that CNV counts in the p arm are less common compared to long arms, and the CNV occurrence and distribution in chromosomes is length independent. This study unraveled the force of independent evolutionary dynamics on genome organization and complexity across chromosomes and populations.
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Variaciones en el Número de Copia de ADN , Genoma Humano/genética , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Algoritmos , Mapeo Cromosómico/métodos , Biología Computacional/métodos , Femenino , Frecuencia de los Genes , Genética de Población/métodos , Técnicas de Genotipaje/métodos , Salud Global , Humanos , Patrón de Herencia , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
BACKGROUND: Several studies have assessed the association between IL-17F and IL-10 promoter polymorphisms and asthma, but the results were conflicting. Furthermore, few studies have evaluated the association of cytokine polymorphisms with asthma and its clinical phenotypes. OBJECTIVE: This study was conducted to evaluate the association of IL-10 (interleukin 10) and IL-17F (interleukin 17F) promoter polymorphisms (rs1800871, rs1800896 and rs1889570) with asthma and its clinical phenotypes including severity, atopic status, spirometric parameters, and response to treatment in south Indian population. A sub-study was conducted to assess cytokine levels in subjects with different gene variants. METHODS: IL-10 and IL-17F polymorphisms were genotyped in 419 asthmatic patients and 393 controls using Mass ARRAY. RESULTS: Our results showed an association between IL-10 SNPs and mild asthma. No association was found with any of three SNPs in moderate to severe asthma. Comparison of genotype distribution of IL-17F rs1887570 AA variant among atopic and non-atopic patients showed significant difference (p = 0.024). Correlation analysis of IL-10 and IL-17F SNPs to clinical variables showed a positive correlation between IL-17F rs1887570 AA and number of allergen sensitized (rs = 0.142, p = 0.004). Significant improvement in lung function was observed after 2 months of ICS (Inhaled corticosteroids) and LABA (long acting ß2 agonist) treatment in all subjects with no statistically significant difference among SNPs variants. Cytokines levels were similar in different SNP variants. CONCLUSION: We observed an association between IL-10 rs1800871 and rs1800896 SNPs and mild asthma, as well as IL-17F rs1887570 AA variant and number of allergens sensitized.
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Asma/genética , Asma/fisiopatología , Interleucina-10/genética , Interleucina-17/genética , Adulto , Alelos , Asma/tratamiento farmacológico , Estudios de Casos y Controles , Femenino , Volumen Espiratorio Forzado , Genotipo , Humanos , Hipersensibilidad Inmediata/genética , India , Interleucina-10/sangre , Interleucina-17/sangre , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Índice de Severidad de la Enfermedad , Espirometría , Capacidad VitalRESUMEN
BACKGROUND & OBJECTIVES: Interleukin 4 (IL4) and IL13 genes are believed to be responsible for inflammation of the airways in asthmatics. These share a common receptor component called IL4Rα which is another potentially important candidate gene linked to asthma phenotypes. Another gene Toll-like receptor 4 (TLR4) might affect the incidence or progression of asthma through the expression of proinflammatory genes. Several single nucleotide polymorphisms (SNPs) in IL4, IL13, IL4Rα and TLR4 have been reported to be linked to asthma or related phenotypes in several ethnic populations using linkage studies and association studies. However, the results have not been consistent. We investigated five SNPs (C-589T and C-33T of IL4, G+2044A of IL13, A+1902G of IL4Rα, and A+896G of TLR4) in patients with adult onset asthma to evaluate their role in manifestation and severity of asthma. METHODS: Adult (>18 yr of age) patients with asthma (n=100) and healthy controls (n=50) were included in the study. Genotyping was performed using sequenom MassARRAY technology. RESULTS: The mutant alleles of the C-589T and C-33T SNPs in the promoter region of IL4 were present in 4 per cent patients with asthma but absent from the control group suggesting that the variations in IL4 may contribute to asthma occurrence. The SNPs of other genes were seen in both controls and patients. INTERPRETATION & CONCLUSIONS: The results suggest the possible association between the genetic distribution of C-589T and C-33T SNPs of IL4 with asthma in Indian adults.
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Asma/genética , Interleucina-13/genética , Subunidad alfa del Receptor de Interleucina-4/genética , Interleucina-4/genética , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 4/genética , Adulto , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Summary Van der Woude syndrome (VWS) is an autosomal dominant developmental malformation presenting with bilateral lower lip pits related to cleft lip, cleft palate and other malformations. We performed a whole-genome copy number variations (CNVs) scan in an Indian family with members suffering from VWS using 2·6 million combined SNP and CNV markers. We found CNVs affecting IRF6, a known candidate gene for VWS, in all three cases, while none of the non-VWS members showed any CNVs in the IRF6 region. The duplications and deletions of the chromosomal critical region in 1q32-q41 confirm the involvement of CNVs in IRF6 in South Indian VWS patients. Molecular network analysis of these and other cleft lip/palate related module genes suggests that they are associated with cytokine-mediated signalling pathways and response to interferon-gamma mediated signalling pathways. This is a maiden study indicating the involvement of CNVs in IRF6 in causing VWS in the Indian population.
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Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 1/genética , Labio Leporino/genética , Fisura del Paladar/genética , Quistes/genética , Dosificación de Gen/genética , Factores Reguladores del Interferón/genética , Labio/anomalías , Citocinas/metabolismo , Genotipo , Humanos , India , Polimorfismo de Nucleótido Simple/genética , Transducción de Señal/genéticaRESUMEN
Copy number variations (CNVs) alter the transcriptional and translational levels of genes by disrupting the coding structure and this burden of CNVs seems to be a significant contributor to phenotypic variations. Therefore it was necessary to assess the complexities of CNV burden on the coding genome. A total of 1715 individuals from 12 populations were used for CNV analysis in the present investigation. Analysis was performed using Affymetrix Genome-Wide Human SNP Array 6·0 chip and CytoScan High-Density arrays. CNVs were more frequently observed in the coding region than in the non-coding region. CNVs were observed vastly more frequently in the coding region than the non-coding region. CNVs were found to be enriched in the regions containing functional genes (83-96%) compared with the regions containing pseudogenes (4-17%). CNVs across the genome of an individual showed multiple hits across many genes, whose proteins interact physically and function under the same pathway. We identified varying numbers of proteins and degrees of interactions within protein complexes of single individual genomes. This study represents the first draft of a population-specific CNV genes map as well as a cross-populational map. The complex relationship of CNVs on genes and their physically interacting partners unravels many complexities involved in phenotype expression. This study identifies four mechanisms contributing to the complexities caused by the presence of multiple CNVs across many genes in the coding part of the genome.
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Variaciones en el Número de Copia de ADN/genética , Genes/genética , Genoma Humano/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Fenotipo , Mapeo Cromosómico/métodos , Humanos , Polimorfismo de Nucleótido Simple/genética , Mapeo de Interacción de ProteínasRESUMEN
BACKGROUND: Asthma is a complex disease caused by gene-gene, gene-protein, and protein-protein interactions and the influence of environment, which plays a significant role in causing asthma pathogenesis. ADAM33 is known to be an important gene involved in asthma pathogenesis. No one single gene is a causal factor of asthma; rather, asthma is caused by a complex interaction of multiple genes having pathogenetic and protective effects. OBJECTIVE: To identify and understand the interacting genes and proteins of ADAM33. METHODS: The Ingenuity Pathway Analysis and GeneMANIA tools and a literature survey were used to identify the interacting candidates of ADAM33 and the WEB-based GEne SeT AnaLysis Toolkit was used to perform enrichment analysis of the proteins identified. RESULTS: Keeping ADAM33 as a major hub, the authors identified some proteins whose interaction with ADAM33 had been associated with asthma and they recognized some proteins, such as amyloid ß (A4) precursor protein, ataxin-7, α4-integrin, α5-integrin, α9-integrin, tissue inhibitor of metalloproteinase-4, and ubiquilin-4, that had not been previously associated with asthma. CONCLUSION: The proteins identified in this study were enriched for various mechanisms that are involved in airway hyperresponsiveness, and through the interaction with ADAM33, they may have potential relevance in asthma.
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Proteínas ADAM/metabolismo , Asma/metabolismo , Hiperreactividad Bronquial/patología , Matriz Extracelular/metabolismo , Redes y Vías Metabólicas , Proteínas ADAM/genética , Asma/genética , Hiperreactividad Bronquial/genética , Células Epiteliales/metabolismo , Fibroblastos/metabolismo , Humanos , Interleucina-13/genética , Interleucina-4/genética , MicroARNs/genética , Miocitos del Músculo Liso/metabolismo , Estructura Terciaria de Proteína , Inhibidores Tisulares de Metaloproteinasas/genéticaRESUMEN
OBJECTIVES: The development of inflammation in asthma involves an intricate network of cytokines that recruit and activate numerous immune cells. This study was aimed to compare serum levels of IL-10, IL-17F, and IL-33 in asthmatic patients and non-asthmatic controls and correlate cytokine levels to asthma severity and various clinical, spirometric, and laboratory variables. METHODS: Using ELISA, serum levels of IL-10, IL-17F, and IL-33 were evaluated in 44 asthmatics (14 mild persistent, 15 moderate persistent, and 15 severe persistent) and 44 controls. RESULTS: This is one of the first reports showing a significant difference in serum levels of asthma-associated cytokines, anti-inflammatory IL-10, and pro-inflammatory IL-17F and IL-33, in the same subset of asthmatic patients. Our results showed diminished level of IL-10 and elevated levels of IL-17F and IL-33 in asthmatics than in controls (p < 0.001). Assessment of cytokine levels between subjects of different gender, age group, and BMI showed non-significant differences. Correlation analysis of cytokine levels to clinical variables showed that IL-17F is associated negatively to FVC % predicted (forced vital capacity) and FEV1% predicted (forced expiratory volume in one second) and positively to number of allergens sensitized and FEV1 reversibility. A strong negative correlation was found between IL-10 and IL-33 levels (p = 0.001). CONCLUSIONS: Negative correlation between IL-10 and IL-33 levels may reflect a converse relationship between anti-inflammatory and pro-inflammatory cytokines in an individually balanced pattern. The association between IL-17F level and asthmatic phenotypes such as reduced FVC and FEV1, higher degree of sensitization, and post-bronchodilator reversibility needs further assessments.
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Asma/inmunología , Interleucina-10/sangre , Interleucina-17/sangre , Interleucinas/sangre , Adulto , Asma/sangre , Asma/fisiopatología , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Volumen Espiratorio Forzado , Humanos , Interleucina-33 , Masculino , Estadísticas no Paramétricas , Capacidad VitalRESUMEN
BACKGROUND: Many studies have been conducted to identify either insertions-deletions (inDels) or copy number variations (CNVs) in humans, but few studies have been conducted to identify both of these forms coexisting in the same region. AIMS AND OBJECTIVES: To map the functionally significant sites within human genes that are likely to influence human traits and diseases. MATERIALS AND METHODS: In this report, we describe an inDel map in the 1051 Tibetan CNV regions obtained through CNV genotyping using Affymetrix Genome-wide single nucleotide polymorphism 6.0 chip. InDel polymorphisms in these copy number polymorphism regions were identified with a computational approach using the 2500 deoxyribonucleic acid sequences obtained from the 1000 Genome Project. RESULTS: The study identified a total of 95935 inDels that range from 1 bp to several bps in length which were found scattered across regulatory regions, exons and in introns of genes underlying the CNVs. A study on the distribution of inDels revealed that the majority of inDels were found in coding regions of the genome than the noncoding, while within the genes, inDels in intron regions were more followed by exonic regions and finally the regulatory regions. CONCLUSION: Study of inDels in CNV regions contribute to the enhanced understanding of the role played by the two variations and their collective influence on the genome. Further, a collection of these inDel genetic markers will aid in genetic mapping, further understanding of the phenotypic variability, identification of disease genes and in detecting novel CNVs.
RESUMEN
Developmental dyslexia (DD) is a complex heritable disorder with unexpected difficulty in learning to read and spell despite adequate intelligence, education, environment, and normal senses. We performed genome-wide screening for copy number variations (CNVs) in 10 large Indian dyslexic families using Affymetrix Genome-Wide Human SNP Array 6.0. Results revealed the complex genomic rearrangements due to one non-contiguous deletion and five contiguous micro duplications and micro deletions at 17q21.31 region in three dyslexic families. CNVs in this region harbor the genes KIAA1267, LRRC37A, ARL17A/B, NSFP1, and NSF. The CNVs in case 1 and case 2 at this locus were found to be in homozygous state and case 3 was a de novo CNV. These CNVs were found with at least one CNV having a common break and end points in the parents. This cluster of genes containing NSF is implicated in learning, cognition, and memory, though not formally associated with dyslexia. Molecular network analysis of these and other dyslexia related module genes suggests NSF and other genes to be associated with cellular/vesicular membrane fusion and synaptic transmission. Thus, we suggest that NSF in this cluster would be the nearest gene responsible for the learning disability phenotype.
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Cromosomas Humanos Par 17/genética , Variaciones en el Número de Copia de ADN/genética , Dislexia/genética , Reordenamiento Génico , Predisposición Genética a la Enfermedad , Genoma Humano , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Hibridación Genómica Comparativa , Familia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Fenotipo , Pronóstico , Adulto JovenRESUMEN
A 3.5-Mb region of the X chromosome underwent duplication and transposition to the Y chromosome ~5-6 Mya. This X-transposed-region (XTR) originated at Xq21.3 and was inserted at Yp11.2. The two locations have 98.78 % homology and a high concentration of tandem repeats. In whole-genome scans of ten large families with dyslexic members, we identified transposed blocks comprising >102 kb of the Yp11.2 region in its homologous region at Xq21.3 in three females from three different families. Although recombination is known to be limited only to the pseudoautosomal regions (PARs) of the X and Y chromosomes, we report allelic unequal recombination between the XTR region Yp11.2 and Xq21.3, indicating the presence of a new PAR, which we named PAR3. This PAR3 region was also found in 2 % of the general population. An additional layer of justification could be provided from six other dyslexic cases which harbored duplications and deletions in the same Xq21.3 and Yp11.2 regions through allelic unequal recombination.
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Cromosomas Humanos X/genética , Cromosomas Humanos Y/genética , Variaciones en el Número de Copia de ADN/genética , Evolución Molecular , Dislexia/genética , Dislexia/fisiopatología , Femenino , Genes Ligados a X , Humanos , LinajeRESUMEN
Drosophila nasuta nasuta (2n = 8) and D. n. albomicans (2n = 6) are morphologically identical, cross fertile and karyotypically dissimilar pair of chromosomal races belonging to nasuta subgroup of immigrans group of Drosophila. Interracial hybridization between these two races yielded karyotypically stabilized newly evolved Cytoraces with new combinations of chromosomes and DNA content, and are called nasuta-albomicans complex of Drosophila. Along with many other features, striking plasticity in the lifespan has been observed in the karyotypically stabilized members of nasuta-albomicans complex of Drosophila. These findings provide a strong background to understand any changes at the molecular levels. In view of this, we cloned and characterized Sod1 and Rpd3 in the members of nasuta-albomicans complex of Drosophila. The evolution of Sod1 and Rpd3 in D. n. nasuta and D. n. albomicans is contrasting with the other species of Drosophila, at the level of synonymous mutations, intron variation, InDels and secondary structure changes in protein. In the members of NAC of Drosophila there were synonymous changes, variations in intron sequences of Sod1, whereas, in Rpd3, synonymous, nonsynonymous, intron variation, and secondary structure changes in protein were observed. The contrasting differences in the levels of Rpd3 (and Sir2) proteins were also noticed among short-lived and long-lived Cytoraces. The Cytoraces have exhibited not only specific changes in Sod1 and Rpd3, but also show pronounced changes in the levels of synthesis of these proteins, which indicates rapid evolution of these Cytoraces in laboratory. Further these Cytoraces have become a model system to understand the process of anagenesis.
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Proteínas de Drosophila/genética , Drosophila/genética , Evolución Molecular , Histona Desacetilasa 1/genética , Mutación , Superóxido Dismutasa/genética , Secuencia de Aminoácidos , Animales , Cromosomas de Insectos , Drosophila/clasificación , Proteínas de Drosophila/clasificación , Histona Desacetilasa 1/clasificación , Humanos , Hibridación Genética , Intrones , Cariotipificación , Longevidad , Masculino , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , Alineación de Secuencia , Superóxido Dismutasa/clasificación , Superóxido Dismutasa-1RESUMEN
Developmental dyslexia (DD) is a heritable, complex genetic disorder associated with impairment in reading and writing skills despite having normal intellectual ability and appropriate educational opportunities. Chromosome 6p23-21.3 at DYX2 locus has showed the most consistent evidence of linkage for DD and two susceptible genes KIAA0319 and DCDC2 for DD at DYX2 locus showed significant association. Specific candidate gene-association studies have identified variants, risk haplotypes and microsatellites of KIAA0319 and DCDC2 correlated with wide range of reading-related traits. In this study, we used a case-control approach for analyzing single-nucleotide polymorphisms (SNPs) in KIAA0319 and DCDC2. Our study demonstrated the association of DD with SNP rs4504469 of KIAA0319 and not with any SNPs of DCDC2.
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Dislexia/genética , Estudios de Asociación Genética , Variación Genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas del Tejido Nervioso/genética , Alelos , Estudios de Casos y Controles , Preescolar , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Humanos , India , Masculino , Modelos Genéticos , Pruebas Neuropsicológicas , Polimorfismo de Nucleótido Simple , LecturaRESUMEN
Genome-wide screening for copy number variations (CNVs) in ten Indian dyslexic families revealed the presence of five de novo CNVs in regions harboring GABARAP, NEGR1, ACCN1, DCDC5, and one in already known candidate gene CNTNAP2. These genes are located on regions of chromosomes 17p13.1, 1p31.1, 17q11.21, 11p14.1 and 7q35, respectively, and are implicated in learning, cognition and memory processes through dendritic spinal plasticity, though not formally associated with dyslexia. Molecular network analysis of these and other dyslexia-related module genes suggests them to be associated with synaptic transmission, axon guidance and cell adhesion. Thus, we suggest that dyslexia may also be caused by neuronal disconnection in addition to the earlier view that it is due to neuronal migrational disorder.
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Variaciones en el Número de Copia de ADN/genética , Espinas Dendríticas/metabolismo , Dislexia/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Plasticidad Neuronal/genética , Adolescente , Niño , Rotura Cromosómica , Familia , Femenino , Ontología de Genes , Humanos , Masculino , Pruebas Neuropsicológicas , Fenotipo , Polimorfismo Genético , Mapas de Interacción de Proteínas/genética , Reproducibilidad de los Resultados , Transducción de Señal/genética , Adulto JovenRESUMEN
BACKGROUND & OBJECTIVES: Socio-economic status is associated with increased morbidity in patients with asthma. The aim of the present study was to assess the association between socio-economic status and family history of asthma in adult asthma patients. METHODS: The study included 200 adults with asthma and 400 non-asthmatic controls. Socio-economic status was determined based on income. Regression analysis was used to estimate odd ratios in relation to socio-economic class, using age, gender, family history of asthma and smoking habits. RESULTS: The highest occurrence of having any family history of asthma was observed in the high class group (88.2%), followed by upper middle class (79.5%), lower middle class (60%) and the lowest in the low class group (34%). Having any family history of asthma was an important risk factor in both univariate and multivariate analyses in lower middle class, upper middle class and high class, but not in the low class group. INTERPRETATION AND CONCLUSIONS: The results indicated a positive association between having a family history of asthma and higher socio-economic status. Further studies on a large representative sample need to be conducted to confirm these findings.
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Asma/epidemiología , Asma/fisiopatología , Clase Social , Factores Socioeconómicos , Adolescente , Adulto , Asma/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Centros de Atención TerciariaRESUMEN
Developmental dyslexia (DD) is a complex heritable disorder with unexpected difficulty in learning to read and spell despite adequate intelligence, education, environment, and normal senses. We performed a whole genome copy number variations (CNV) scan on 11 dyslexic families consisting of 14 dyslexic subjects and 24 non dyslexic members using 1.8 million combined SNP and CNV markers. We found CNVs affecting protocadherin genes in six dyslexics from three families, while none among the non-dyslexic control members showed any CNV in protocadherins. We identified duplications in five cases and a deletion in one case in Xq21.3 region bearing PCDH11X. Unequal recombination between the X-transposed region (XTR) of Yp11.2 and the X chromosome might be causing these structural changes. PCDH11X, expressed in brain is implicated in cell-cell communication, verbal ability, cerebral asymmetry, and dendritic synaptic plasticity, may be regarded as a new candidate gene for dyslexia.
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Cadherinas/genética , Variaciones en el Número de Copia de ADN/genética , Dislexia/genética , Predisposición Genética a la Enfermedad , Genoma Humano/genética , Mutación/genética , Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Adolescente , Anciano , Rotura Cromosómica , Deleción Cromosómica , Duplicación Cromosómica/genética , Familia , Femenino , Humanos , India , Masculino , Modelos Genéticos , Linaje , Protocadherinas , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
ADAM33 has been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of ADAM33 SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case-control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of ADAM33, namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392. We studied the association with asthma and treatment responsiveness to ICS+LABA, using genotype, allele frequency distribution, and haplotype analysis. A significant clinical finding of the study was that certain patients in the disease severity group (moderate and mild) showed poor or no improvement after a three-month follow-up of regular ICS+LABA therapy. Of the studied ADAM33 SNPs, rs2853209 showed an association with asthma. The further analysis of asthma patients according to disease severity suggested an association between moderate disease and the minor allele "T" for rs2853209. The homozygous minor allele of SNP rs2787094 was found to be associated with poorer lung function and the least lung-function improvement after three months of ICS+LABA therapy. The haplotype analysis of six SNPs showed a significant association between the rs2853209 and rs3918396 blocks and asthma. ADAM33 gene polymorphism has clinical relevance in terms of disease association and response to treatment. SNP rs2853209 seemed most relevant to asthma, and SNP rs2787094 could be a genetic marker for predicting response to ICS+LABA therapy in the study population.
RESUMEN
Serum protein analysis for noninvasive quantification of airway inflammation in asthma is a promising research tool in the field of lung diseases. Cytokines are believed to have major role in inflammatory process of the airways of the lung. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4 and interleukin (IL)-13, and Th1 cells, which secrete interferon (IFN)-gamma in asthma. To test the hypothesis that serum IL-13 and IL-4 levels may be elevated whereas IFN-gamma would be decreased in this cohort of patients, a property that could make them possible candidate biomarkers in determining asthma occurrence and severity, we measured concentrations of IL-4, IL-13 and IFN-gamma in serum samples of 88 subjects (44 normal, 12 with mild asthma, 16 with moderate asthma, and 16 with severe asthma). Serum Levels of IL-4, IL-13, and IFN-gamma were determined by an enzyme-linked immune-sorbent assay (ELISA). Median serum level of IFN-gamma in asthmatic patients was 8.0 pg/ml, while it was 11.4 pg/ml in healthy controls. However, the difference was not significant. Among the different age groups in whom IFN-gamma was assessed, the highest median value in both cases and controls was observed in the age group of 31-40 years. The median serum level of IL-13 was 40.0 pg/ml in asthmatic patients and 58.25 pg/ml in healthy controls. The difference was not significant. On subgroup analysis, no significant difference of IFN-gamma and IL-13 between asthma of different severities was observed. The study also revealed nonsignificant difference of serum cytokines with the duration of asthma, number of allergens, and severity of sensitization. Normal serum levels of IFN-gamma and IL-13 in asthmatic patients suggest their neutral role in the inflammatory process; however, more studies are required to establish the effect of these cytokines in adulthood asthma in different ethnic populations.