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Hernandez-Lemus E.,National Institute of Genomic Medicine INMEGEN | Hernandez-Lemus E.,National Autonomous University of Mexico
Journal of Physics: Conference Series | Year: 2013

Recent years have witnessed the development of new quantitative approaches and theoretical tenets in the biological sciences. The advent of high throughput experiments in genomics, proteomics and electrophysiology (to cite just a few examples) have provided the researchers with unprecedented amounts of data to be analyzed. Large datasets, however can not provide the means to achieve a complete understanding of the underlying biological phenomena, unless they are supplied with a solid theoretical framework and with proper analytical tools. It is now widely accepted that by using and extending some of the paradigmatic principles of what has been called complex systems theory, some degree of advance in this direction can be attained. We will be presenting ways in which by using data integration techniques (linear, non-linear, combinatorial, graphical), multidimensional-multilevel descriptions (multifractal modeling, dimensionality reduction, computational learning), as well as an approach based in systems theory (interaction maps, probabilistic graphical models, non-equilibrium physics) have allowed us to better understand some problems in the interface of Statistical Physics and Computational Biology.

Posadas-Sanchez R.,National Institute of Cardiology Ignacio Chavez INCICH | Posadas-Romero C.,National Institute of Cardiology Ignacio Chavez INCICH | Ocampo-Arcos W.A.,National Institute of Cardiology Ignacio Chavez INCICH | Villarreal-Molina M.T.,National Institute of Genomic Medicine INMEGEN | And 7 more authors.
International Journal of Molecular Medicine | Year: 2014

Epidemiological and clinical studies have shown that a low plasma high-density lipoprotein cholesterol (HDL-C) level is a strong predictor of cardiovascular disease (CVD). Lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the formation, maturation and function of HDL. Therefore impaired LCAT function may enhance atherosclerosis because of defective cholesterol transport. In this study, we examined a 34-year old LCAT-deficient patient and eight first-degree family members. There was a strong family history for CVD and type 2 diabetes mellitus (DM2). The proband was found homozygous for a previously reported LCAT gene mutation (Thr37Met). A sister and two sons of the proband were heterozygous for the same mutation. The proband had DM2 and showed severe multivessel coronary artery disease, corneal opacification and extremely low HDL-C levels. Large HDL particles were absent while small HDL particles were increased. The HDL of the patient had a reduced ability to promote cell cholesterol efflux, and the low-density lipoproteins (LDL) were more susceptible to oxidation. Among his family members, two heterozygotes and one non-carrier had early carotid or coronary atherosclerosis. In conclusion, as the increased LDL oxidability and structural and functional abnormalities of HDL particles have been reported in patients with obesity and diabetes, the results suggested that the adverse coronary risk profile, and not being LCAT deficient, may be responsible for the CVD found in our proband, and for the early atherosclerosis observed in the two heterozygotes and in the wild-type family members.

Balam-Ortiz E.,National Institute of Genomic Medicine INMEGEN | Balam-Ortiz E.,PEMEX | Esquivel-Villarreal A.,PEMEX | Huerta-Hernandez D.,SEDENA Central Military Hospital | And 13 more authors.
Hypertension | Year: 2012

The angiotensinogen gene locus has been associated with essential hypertension in most populations analyzed to date. Increased plasma angiotensinogen levels have been proposed as an underlying cause of essential hypertension in whites; however, differences in the genetic regulation of plasma angiotensinogen levels have also been reported for other populations. The aim of this study was to analyze the relationship between angiotensinogen gene polymorphisms and haplotypes with plasma angiotensinogen levels and the risk of essential hypertension in the Mexican population. We genotyped 9 angiotensinogen gene polymorphisms in 706 individuals. Four polymorphisms, A-6, C4072, C6309, and G12775, were associated with increased risk, and the strongest association was found for the C6309 allele (χ2=23.9; P=0.0000009), which resulted in an odds ratio of 3.0 (95% CI: 1.8-4.9; P=0.000006) in the recessive model. Two polymorphisms, A-20C (P=0.003) and C3389T (P=0.0001), were associated with increased plasma angiotensinogen levels but did not show association with essential hypertension. The haplotypes H1 (χ2=8.1; P=0.004) and H5 (χ2=5.1; P=0.02) were associated with essential hypertension. Using phylogenetic analysis, we found that haplotypes 1 and 5 are the human ancestral haplotypes. Our results suggest that the positive association between angiotensinogen gene polymorphisms and haplotypes with essential hypertension is not simply explained by an increase in plasma angiotensinogen concentration. Complex interactions between risk alleles suggest that these haplotypes act as "superalleles." © 2012 American Heart Association, Inc.

Balam-Ortiz E.,National Institute of Genomic Medicine INMEGEN | Esquivel-Villarreal A.,Central North Hospital | Alfaro-Ruiz L.,National Institute of Genomic Medicine INMEGEN | Carrillo K.,National Institute of Genomic Medicine INMEGEN | And 5 more authors.
American Journal of the Medical Sciences | Year: 2011

The plasmatic angiotensinogen (AGT) level has been associated with essential hypertension. Linkage analysis has found a relationship between the AGT gene locus and hypertension in the Mexican-American population, but studies have failed to identify genetic variants associated with hypertension or plasma AGT levels. This study analyzes the relationship between polymorphisms in the AGT gene and plasmatic AGT levels in Mexican population. Methods: Nine polymorphisms in AGT gene were genotyped, and plasma AGT level was determined by enzyme-linked immunosorbent assay. Results: Differences in AGT plasma levels were associated with 2 polymorphisms: T-20G, TT = 25.3 ± 8.3 versus TG + GG = 21.6 ± 8.8 μg/mL; P = 0.008 and C3389T (T174M), CC = 25.8 ± 9.9 versus TC + TT = 20.5 ± 5.4 μg/mL; P = 0.0002. Haplotype 2 was associated with low plasma AGT (-5.1 μg/mL [95% confidence interval: -8.6 to -1.6], P = 0.004) and Haplotype 8 was associated with high plasma AGT (6.5 μg/mL [95% confidence interval: 2.5 to 10.6], P = 0.001). This association remained after adjustment for covariates. A Likelihood Ratio Test for haplotype-phenotype association adjusted for covariates resulted in χ = 38.9, P = 0.0005. The total effect of the haplotypes on plasma AGT level variance was 19.5%. No association was identified between haplotypes and quantitative traits of blood pressure. Conclusions: Two polymorphisms (T-20G and C3389T) and 2 haplotypes (H2 and H8) showed an association with plasma AGT levels in Mexican population. Copyright © by the Southern Society for Clinical Investigation.

Tovar H.,National Institute of Genomic Medicine INMEGEN | Garcia-Herrera R.,National Institute of Genomic Medicine INMEGEN | Espinal-Enriquez J.,National Institute of Genomic Medicine INMEGEN | Espinal-Enriquez J.,National Autonomous University of Mexico | And 2 more authors.
Computational Biology and Chemistry | Year: 2015

Gene regulatory networks account for the delicate mechanisms that control gene expression. Under certain circumstances, gene regulatory programs may give rise to amplification cascades. Such transcriptional cascades are events in which activation of key-responsive transcription factors called master regulators trigger a series of gene expression events. The action of transcriptional master regulators is then important for the establishment of certain programs like cell development and differentiation. However, such cascades have also been related with the onset and maintenance of cancer phenotypes. Here we present a systematic implementation of a series of algorithms aimed at the inference of a gene regulatory network and analysis of transcriptional master regulators in the context of primary breast cancer cells. Such studies were performed in a highly curated database of 880 microarray gene expression experiments on biopsy-captured tissue corresponding to primary breast cancer and healthy controls. Biological function and biochemical pathway enrichment analyses were also performed to study the role that the processes controlled - at the transcriptional level - by such master regulators may have in relation to primary breast cancer. We found that transcription factors such as AGTR2, ZNF132, TFDP3 and others are master regulators in this gene regulatory network. Sets of genes controlled by these regulators are involved in processes that are well-known hallmarks of cancer. This kind of analyses may help to understand the most upstream events in the development of phenotypes, in particular, those regarding cancer biology. © 2015 Elsevier Ltd.

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