RESUMEN
BACKGROUND: The beneficial effect of a climatic treatment in children with asthma was established quite some time ago, but the mechanism of this beneficial effect has not been fully elucidated. We investigated the role of the cytokines of the TH2 pathway, reactive oxygen species (ROS) and reactive nitrogen species (RNS) over the course of a high-altitude climatic therapy. METHODS: A group of 67 children originating from various French towns suffering from uncontrolled severe asthma was sent via their medical specialists, to the Briançon climatic area. They were monitored over the course of an entire school year. During this time, they returned home for 15 days during the Christmas holidays. At each stage, assessment of asthma control, lung function examination (peak flow meter and spirometry), and measurement of exhaled NO, ROS and RNS in exhaled breath condensate (EBC), and the level of cytokines in the plasma of the TH2 pathway were carried out. RESULTS: The degree of asthma control improved at high altitude and worsened upon returning home. The average value of the peak expiratory flow also improved during the first 3 months but then worsened upon returning home, while the other spirometric parameters did not change. The level of expired NO and the scores for quality of life underwent a similar change. The level of RNS and ROS in the EBC did not change significantly. Besides, a marked and statistically significant decrease in the level of IL-13 and IL-10 was noted. CONCLUSION: The beneficial effect of a climatic stay of children suffering from allergic asthma at altitude appears to be linked with less allergenic stimulation.
Asunto(s)
Altitud , Asma , Asma/tratamiento farmacológico , Pruebas Respiratorias , Niño , Espiración , Humanos , Calidad de VidaRESUMEN
The domestic dog offers a remarkable opportunity to disentangle the genetics of complex phenotypes. Here, we explore a locus, previously identified in the Portuguese water dog (PWD), associated with PC2, a morphological principal component characterized as leg width versus leg length. The locus was initially mapped to a region of 26 Mb on canine chromosome 12 (CFA12) following a genome-wide scan. Subsequent and extensive genotyping of single-nucleotide polymorphisms (SNPs) and haplotype analysis in both the PWD and selected breeds representing phenotypic extremes of PC2 reduced the region from 26 Mb to 500 kb. The proximity of the critical interval to two collagen genes suggests that the phenotype may be controlled by cis-acting mechanisms.
Asunto(s)
Perros/anatomía & histología , Perros/genética , Extremidades/anatomía & histología , Animales , Mapeo Cromosómico , Estudios de Asociación Genética , Estudio de Asociación del Genoma Completo , Haplotipos , Fenotipo , Polimorfismo de Nucleótido Simple , Sitios de Carácter CuantitativoRESUMEN
Pinschers affected by coat color dilution show a specific pigmentation phenotype. The dilute pigmentation phenotype leads to a silver-blue appearance of the eumelanin-containing fur and a pale sandy color of pheomelanin-containing fur. In Pinscher breeding, dilute black-and-tan dogs are called "blue," and dilute red or brown animals are termed "fawn" or "Isabella fawn." Coat color dilution in Pinschers is sometimes accompanied by hair loss and a recurrent infection of the hair follicles. In human and mice, several well-characterized genes are responsible for similar pigment variations. To investigate the genetic cause of the coat color dilution in Pinschers, we isolated BAC clones containing the canine ortholog of the known murine color dilution gene Mlph. RH mapping of the canine MLPH gene was performed using an STS marker derived from BAC sequences. Additionally, one MLPH BAC clone was used as probe for FISH mapping, and the canine MLPH gene was assigned to CFA25q24.
Asunto(s)
Mapeo Cromosómico/veterinaria , Cromosomas de los Mamíferos/genética , Perros/genética , Color del Cabello/genética , Proteínas/genética , Animales , Humanos , Hibridación Fluorescente in Situ/métodos , FenotipoRESUMEN
The analysis of inherited diseases in the domestic dog (Canis familiaris) provides a resource for the continued use of this species as a model system for human diseases. Many different dog breeds are affected by congenital sensorineural deafness. Since mutations in various genes have already been found causative for sensorineural hearing impairment in humans or mice, 20 of these genes were considered as candidates for deafness in dogs. For each of the candidate genes a canine BAC clone was isolated by screening with heterologous human or murine cDNA probes. The gene-containing BAC clones were physically assigned to the canine genome by FISH and the BAC-derived STS-markers were positioned with the RHDF5000 panel on the canine RH map. The mapping data, which confirm the established conservation of synteny between canine and human chromosomes, provide a resource for further association studies in segregating canine populations and the basis for new insights into this common canine and human disease.
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Sordera/veterinaria , Predisposición Genética a la Enfermedad , Pérdida Auditiva Sensorineural/veterinaria , Animales , Mapeo Cromosómico/veterinaria , Sordera/genética , Perros , Pérdida Auditiva Sensorineural/genética , Humanos , Hibridación Fluorescente in Situ/veterinaria , Mapeo de Híbrido por Radiación/veterinaria , SinteníaAsunto(s)
Mapeo Cromosómico/métodos , Cromosomas de los Mamíferos/genética , Perros/genética , Cadenas Pesadas de Miosina/genética , Miosina Tipo V/genética , Animales , Cromosomas Artificiales Bacterianos/genética , Biblioteca Genómica , Hibridación Fluorescente in Situ , Mapeo de Híbrido por RadiaciónRESUMEN
Radiation hybrid (RH) map construction allows investigators to locate both type I and type II markers on a given genome map. The process is composed of two steps. The first consists of determining the pattern distribution of a set of markers within the different cell lines of an RH panel. This is mainly done by polymerase chain reaction (PCR) amplification and gel electrophoresis, and results in a series of numbers indicating the presence or the absence of each marker in each cell line. The second step consists of a comparison of these numbers, using various algorithms, to group and then order markers. Because different algorithms may provide (slightly) different orders, we have compared the merits of the MultiMap and TSP/CONCORDE packages using a data set of information currently under analysis for construction of the canine genome RH map.
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Mapeo de Híbrido por Radiación/métodos , Programas Informáticos , Animales , PerrosAsunto(s)
Proteínas de la Matriz Extracelular/genética , Glicoproteínas de Membrana/genética , Animales , Mapeo Cromosómico , Cromosomas Artificiales Bacterianos/genética , Cromosomas de los Mamíferos/genética , Sordera/genética , Sordera/veterinaria , Enfermedades de los Perros/genética , Perros , Hibridación Fluorescente in Situ , Mapeo de Híbrido por RadiaciónAsunto(s)
Cadherinas/genética , Cromosomas de los Mamíferos/genética , Perros/genética , Animales , Proteínas Relacionadas con las Cadherinas , Mapeo Cromosómico , Cromosomas Artificiales Bacterianos/genética , Humanos , Hibridación Fluorescente in Situ , Mapeo de Híbrido por Radiación , Especificidad de la EspecieAsunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas Portadoras/genética , Perros/genética , Animales , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Artificiales Bacterianos/genética , Cartilla de ADN/genética , Drosophila/genética , Forminas , Humanos , Hibridación Fluorescente in Situ , Mapeo de Híbrido por Radiación , Especificidad de la EspecieAsunto(s)
Mapeo Cromosómico/veterinaria , Perros/genética , Células Híbridas/efectos de la radiación , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/genética , Animales , Secuencia de Bases , Cartilla de ADN , Canal de Potasio KCNQ3 , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
Mutations in Cu/Zn superoxide dismutase (SOD1), a major cytosolic antioxidant enzyme in eukaryotic cells, have been reported in approximately 20% of familial amyotrophic lateral sclerosis (FALS) patients. Hereditary canine spinal muscular atrophy (HCSMA), a fatal inherited motor neuron disease in Brittany spaniels, shares many clinical and pathological features with human motor neuron disease, including FALS. The SOD1 coding region has been sequenced and cloned from several animal species, but not from the dog. We have mapped the chromosomal location, sequenced, and characterized the canine SOD1 gene. Extending this analysis, we have evaluated SOD1 as a candidate for HCSMA. The 462 bp SOD1 coding region in the dog encodes 153 amino acid residues and exhibits more than 83% and 79% sequence identity to other mammalian homologues at both the nucleotide and amino acid levels, respectively. The canine SOD1 gene maps to CFA31 close to syntenic group 13 on the radiation hybrid (RH) map in the vicinity of sodium myo/inositol transporter (SMIT) gene. The human orthologous SOD1 and SMIT genes have been localized on HSA 21q22.1 and HSA 21q21, respectively, confirming the conservation of synteny between dog syntenic group 13 and HSA 21. Direct sequencing of SOD1 cDNA from six dogs with HCSMA revealed no mutations. Northern analysis indicated no differences in steady-state levels of SOD1 mRNA.
Asunto(s)
Enfermedades de los Perros/genética , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/veterinaria , Superóxido Dismutasa/genética , Secuencia de Aminoácidos , Esclerosis Amiotrófica Lateral/enzimología , Esclerosis Amiotrófica Lateral/genética , Animales , Secuencia de Bases , Enfermedades de los Perros/enzimología , Perros , Humanos , Datos de Secuencia Molecular , Atrofia Muscular Espinal/enzimología , Mapeo de Híbrido por Radiación , Superóxido Dismutasa-1RESUMEN
Mutations in the gene for gamma-sarcoglycan (SGCG) located on HSA 13q12 are responsible for limb girdle muscular dystrophy (LGMD2C) in human. Here we report the cloning of the canine SGCG gene together with its genomic structure and several intragenic polymorphisms. The coding part of the canine SGCG contains seven exons spanning at least 70 kb of genomic DNA. The chromosome assignment of the canine SGCG gene to CFA 25q21-->q23 confirms that the canine syntenic group 10 corresponds to CFA 25 and also supports the findings of human-canine reciprocal chromosome painting.
Asunto(s)
Cromosomas/genética , Proteínas del Citoesqueleto/genética , Perros/genética , Glicoproteínas de Membrana/genética , Mapeo Físico de Cromosoma , Animales , Secuencia de Bases , Pintura Cromosómica , Clonación Molecular , ADN Complementario/genética , Exones/genética , Humanos , Intrones/genética , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple/genética , Sitios de Empalme de ARN/genética , Mapeo de Híbrido por Radiación , SarcoglicanosRESUMEN
The effects of lactulose and lactitol (2 x 10 g/d) were studied in 36 healthy volunteers in comparison to placebo. All parameters studied were affected by both treatments, lactulose in general leading to more pronounced changes compared to lactitol. Probiotic bacteria were increased, and putrefactive bacteria and potential pathogens were significantly reduced. These variations in colonic flora had the following consequences: (i) a reduced activity of pro-carcinogenic enzymes: azoreductase, 7 alpha-dehydroxylase, beta-glucuronidase, nitroreductase and urease activity; (ii) a global increase of short-chain fatty acids in faeces; (iii) an effect on pH and moisture of faeces, and (iv) also on aromatic compounds such as phenol, cresol, indole and skatol. The findings suggest that lactulose and lactitol are not comparable in their effect on the colonic microflora, its metabolism, and the consequent probiotic effects on human health. The differences found may also be of clinical relevance suggesting that neither compound is equipotent.