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Porto Alegre, Brazil

Dos Anjos J.C.S.,Federal University of Rio Grande do Sul | Filho B.R.,Federal University of Rio Grande do Sul | Barros J.F.,Federal University of Rio Grande do Sul | Schemmer R.B.,Federal University of Rio Grande do Sul | And 2 more authors.
ICEIS 2015 - 17th International Conference on Enterprise Information Systems, Proceedings | Year: 2015

The development of sophisticated sequencing machines and DNA techniques has enabled advances to be made in the medical field of genetics research. However, due to the large amount of data that sequencers produce, new methods and programs are required to allow an efficient and rapid analysis of the data. MapReduce is a data-intensive computing model that handles large volumes that are easy to program by means of two basic functions (Map and Reduce). This work introduces GMS, a genetic mapping system that can assist doctors in the clinical diagnosis of patients by conducting an analysis of the genetic mutations contained in their DNA. As a result, the model can offer a good method for analyzing the data generated by sequencers, by providing a scalable system that can handle a large amount of data. The use of several medical databases at the same time makes it possible to determine susceptibilities to diseases through big data analysis mechanisms. The results show scalability and offer a possible diagnosis that can improve the genetic diagnosis with a powerful tool for health professionals.

Habekost C.T.,Federal University of Rio Grande do Sul | Habekost C.T.,Instituto Nacional Of Genetica Medica Populacional Inagemp | Schestatsky P.,Federal University of Rio Grande do Sul | Torres V.F.,Neurology Service | And 14 more authors.
Orphanet Journal of Rare Diseases | Year: 2014

Background: Neurologic impairments in female heterozygotes for X-linked Adrenoleukodystrophy (X-ALD) are poorly understood. Our aims were to describe the neurological and neurophysiological manifestations of a cohort of X-ALD heterozygotes, and to correlate them with age, disease duration, mutations, X-inactivation and serum concentrations of a marker of neuronal damage, neuron-specific enolase (NSE). Methods. All 45 heterozygotes identified in our region, with previous VLCFA and molecular diagnosis, were invited to be evaluated through myelopathy scales JOA and SSPROM, nerve conduction studies and somatosensory evoked responses. X inactivation pattern was tested by HUMARA methylation assay. Serum NSE was measured by eletrochemiluminescense. Results: Thirty three heterozygote women were recruited: 29 (87%) were symptomatic. Symptomatic and asymptomatic women presented different m ± sd ages (43.9 ± 10.2 versus 24.3 ± 4.6), JOA (14.5 ± 1.7 versus 16.6 ± 0.2) and SSPROM (86.6 ± 7.9 versus 98.4 ± 1.1) scores (p < 0.05). Both JOA (r = -0.68) and SSPROM (r = -0.65) correlated with age, irrespectively of the disease status (p = 0.0001, Spearman). Delayed latencies in the central ascending conduction studies on the lower limbs were present in 72% of all heterozygotes, and correlated with SSPROM (r = -0.47, p = 0.018, Spearman). NSE values were higher in heterozygote than in control women (12.9 ± 7 and 7.2 ± 7 ng/ml, p = 0.012, Mann-Whitney U). Mutation severity and inactivation patterns were not associated with neurologic status. Conclusion: Neurologic manifestations, clearly related to age, were quite common in the present cohort. JOA and SSPROM scales were able to discriminate the asymptomatic from the symptomatic heterozygotes. Both scales might be useful tools to follow disease progression, in future studies. © 2014 Habekost et al.; licensee BioMed Central Ltd.

Habekost C.T.,Genetics and Molecular Biology | Habekost C.T.,Instituto Nacional Of Genetica Medica Populacional Inagemp | Pereira F.S.,Laboratory of Genetic Identification | Vargas C.R.,Genetics and Biochemistry | And 12 more authors.
Metabolic Brain Disease | Year: 2015

X-linked adrenoleukodystrophy heterozygote women can present adult onset myeloneuropathy and little is known about its natural history. We aimed to describe the progression rate of the neurological impairment in the prospective follow-up of our cohort and to look for prognostic factors. The neurological scales Japanese Orthopaedic Association (JOA) and Severity Score System for Progressive Myelopathy (SSPROM) were applied at baseline in 29 symptomatic carriers and in follow-up visits. Age at onset, disease duration, X inactivation pattern, determination of the allele expressed, plasma levels of the very long chain fatty acids and of the neuron-specific enolase, and somato-sensory evoked potentials, were taken at baseline. The slope of the linear regression of both JOA and SSPROM versus disease duration since the first symptom was estimated using mixed modeling. JOA and SSPROM decreased 0.42 and 1.87 points per year, respectively (p < 0.001). None of the parameters under study influenced these rates. We estimated that the number of carriers per arm needed in a future 12 month trial with 80 % power and a 50 % reduction in disease progression would be 225 women for JOA and 750 for SSPROM. The progression rates of the studied neurological scales were small, did not depend on any modifier factor known, and reflected the characteristically slow worsening of symptoms in X-ALD heterozygotes. Better biomarkers are still necessary for future studies. © 2015, Springer Science+Business Media New York.

Rivera-Meza M.,Laboratory of Gene Therapy | Quintanilla M.E.,University of Chile | Tampier L.,University of Chile | Mura C.V.,Millennium Institute for Cell Dynamics and Biotechnology | And 4 more authors.
FASEB Journal | Year: 2010

Humans who carry a point mutation in the gene coding for alcohol dehydrogenase-1B (ADH1B*2; Arg47His) are markedly protected against alcoholism. Although this mutation results in a 100-fold increase in enzyme activity, it has not been reported to cause higher levels of acetaldehyde, a metabolite of ethanol known to deter alcohol intake. Hence, the mechanism by which this mutation confers protection against alcoholism is unknown. To study this protective effect, the wild-type rat cDNA encoding rADH-47Arg was mutated to encode rADH-47His, mimicking the human mutation. The mutated cDNA was incorporated into an adenoviral vector and administered to genetically selected alcohol-preferring rats. The V max of rADH-47His was 6-fold higher (P<0.001) than that of the wild-type rADH-47Arg. Animals transduced with rAdh-47His showed a 90% (P<0.01) increase in liver ADH activity and a 50% reduction (P<0.001) in voluntary ethanol intake. In animals transduced with rAdh-47His, administration of ethanol (1g/kg) produced a short-lived increase of arterial blood acetaldehyde concentration to levels that were 3.5- to 5-fold greater than those in animals transduced with the wild-type rAdh-47Arg vector or with a noncoding vector. This brief increase (burst) in arterial acetaldehyde concentration after ethanol ingestion may constitute the mechanism by which humans carrying the ADH1B*2 allele are protected against alcoholism. © FASEB.

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