HUMAN GENETICS

Author: CASALS SENENT TERESA.
Year: 2003.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.

Author: ALEGRET COLOMÉ JOSEP MARIA.
Year: 2003.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: ESCUELA DE POSTGRADO.

Author: GALLARDO SAINZ DOMINGO.
Year: 2003.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: CENTRE DE TRANSFUSIÓ I BANC DE TEIXISTS.

Summary: It has developed a technique that allows simplified nucleotide sequencing analysis of all relevant regions of the gene FVIII in a rapid and sensitive. This has allowed the development of a protocol optimized for the molecular diagnosis of hemophilia A direct that has shown great durability and reliability, it has been implanted in the routine following the ISO-9001: 2000. It also has developed a rapid method for the molecular diagnosis of the direct hemofília B based on the systematic analysis of the relevant gene sequences nucleotídicas FIX. It has been shown the sensitivity of the method after being successfully implemented from genetic material extracted from the root of a single hair. As in the case of hemophilia A, this method has been implemented in the laboratory according to the ISO-9001: 2000 certifying the quality of the diagnostic activity. These new strategies have enabled the identification of a total of 56 mutations in patients with haemophilia from the Spanish population, 10 of which are for hemophilia B and 46 to hemophilia A. The latter have been sent to the International Registration of mutations in hemophilia A (HAMSTeRS). We have delivered a total of 16 new mutations, 2 associated with hemophilia B and 14 to hemophilia A. The mutation 2409delT was the first mutation published in a journal of international and registered at the base of mutations HMATeRS by a Spanish group. On the other hand it has become clear that the identification of the mutation allows diagnosis of a high percentage of families suffering from haemophilia by applying the technique of PCR-RFLP (about 75% in our study). Finally has been characterized for the first time a mutation responsible for the emergence of a congenital coagulopathy originated as a result of unequal homologous recombination between Alu sequences. This recombination, mediated by elements belonging to different families Alu located in introns adjacent gene FVIII, caused a great delección of about 23 Kb which includes the entire exon 25. Two possible mechanisms are involved: recombination by mating intracromosómico or by uneven alignment between sister chromatids.

Author: SALIDO OLIVARES MARINA.
Year: 2004.
University: CÓRDOBA [www.uco.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: OBJECTIVE: To determine whether the MHC polymorphism is associated with response to treatment with Infliximab in RA. PACIENTESY METHODS: We included 78 patients with RA refractory to prior treatment with other FAMEs, who were treated with infliximab consecutively from 2001 to 2002 in services Reumatologíadel Clinical Hospital San Carlos and La Paz in Madrid. As a control group were employed 342 people. Clinical variables were collected and analytical prior to therapy and 3 months of initiation. It was considered patient responder (AB), if there was an improvement equaled more than 50% of the initial value of the NAO, NAT And two or more of these criteria: CRP, ESR, HAQ or VAS. It was also felt if PR showed a 25% improvement from baseline absolute DAS 28. At one year was assessed the degree of sustained response. The study bivariate baseline characteristics of test was used? 2 and Student's t, depending on whether the variable was qualitatively or quantitatively. The genetic study was used? 2 and odds, and pruebaexactade Fisher in cases expected menoresde 5. RESULTS: Presentaban an average of 56.88 years (22-88 years), the predominance of women (76.9%), mean duration of RA for 10 years and FR + in a 84.62%. Most treated with combination therapy. All presented criteria activity at the beginning. After therapy were considered PR 41 Ycomo NRP 37. A year retained terapia56 patients (35 PR Y21 NRP). The microsatellite TNF haplotypes were not differences, except TNF a11b4c1d3e3 (41% and 16% PR NRP). Nor had the alleles of epítopo shared and microsatellites MICA, 06S2223 and BAT2. The only allele plus NRP was 06S273_3 (p = 0.04, OR = 0.37). This allele is associated with BAT2_2 in population control. In our case, this association was in the NRP (85%) but not in PR (46%), p = 0.02. In the PR associated the 06S273- 4 with BAT2_2 (17 of 37 vs. 4 of the 35 NRP, OR = 6.39 and p = 0001). With regard to the control group only associated with PR (OR = 4.27 Yp = 0.00002), and therefore with the favorable response to therapy. It seems that there is a haplotype largest PR formed by 06S273_3, BAT2_2 and TNF a11b4c1d3e3 (OR = 10.93, P = 0009). Even seems to be associated with the presence of ORB1 * 0404. CONCLUSIONS: There were no differences in the distribution of alleles of epítopo shared polymorphisms in the promoter of TNFa or microsatellites YMCA and 06S2223. The 06S273_3 is the only plus NRP and is associated with BAT 2_2 in population control. The alleles BAT2_2 And 06S273- 4 are increased only in PR, formed haplotype with TNF a11 b4c1 d3e3 and, therefore, is associated with a favorable response to treatment with Infliximab. There are markers in the MHC that can predict clinical response to treatment with infliximab in short term RA patients refractory to other FAME.

Author: PRIEGO CUADRA TERESA.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FAC. DE MEDICINA.

Summary: During inflammation shaft somatotropo is inhibited. The administration of LPS is used as the experimental model of inflammation and sepsis. The LPS results in a decline in serum growth factor similar to insulin (IGF-I). The IGF-I is regulated by growth hormone (GH) and the protein binding to this serum, IGFBP-3. During the ignition is activated the shaft hipotálamo-hipófiso-adrenal (HHA) releasing gluccoritcoides and induces the synthesis of another important regulator of the inflammatory process, nitric oxide (NO). Both compounds can be mediating inhibition of IGF-I induced by the administration of LPS. Therefore, the goals set were studying the effect of the administration of LPS on the shaft somatotropo and analyze the role of the trigger shaft HHA and the increase in NO in the process. Hypothalamic level, the administration of LPS, the gene activates the expression of somatostatin. This stimulating effect of LPS on the hypothalamic somatostatin is mediated by the increase in the release of NO. At pituitary, LPS, at low doses, it has a stimulating effect on the secretion of GH. At high doses, reduced secretion of pituitary GH. The administration of LPS has a direct inhibitory effect on the hepatic expression of genes GH receptor, IGF-Iy of IGFBP-3. The decrease in IGFBP-3 circulating contributes to the decrease in serum levels of IGF-I. The increased NOT occurring after administration of LPS plays an important role in the inhibition of hepatic expression of genes of IGF-Iy of IGFBO-3. The increase in glucocorticoid after administration of LPS not half this inhibition, but has a protective effect.

Author: MARTÍNEZ GARAY ISABEL.
Year: 2004.
University: VALENCIA [www.uv.es].
Place of defense: BIBLIOTECA DEL CAMPUS DE BURJASSOT.
Place of preparation: FACULTAD DE CIENCIAS BIOLÓGICAS.

Summary: Mental retardation is a social and health problem that is growing in both directions, when it is a condici6n hereditary. Various studies indicate that for years, in Concrete, mental retardation linked to the X chromosome is one of the leading causes of psychological deficit mild and moderate, with a cumulative incidence is estimated at 1: 300 to 1: 600 boys. This paper has dealt with the analysis of several families affected late mentalligado to X, both forms inespecíficas as sindr6micas. The analysis has focused primarily on doS regions: Xp22 in 10S cases inespecíficos and Xq11.4 in syndromic, but also have been analyzed two genes in Xq24-q25. In Xp22 and Xp11.4 have studied 13 genes respectively habiendóse identified in a family of a change in one (FLl14503), which is not present in sequence databases or in healthy individuals. His analysis has made it possible to classify the protein coding as a new protein associated with microtUbulos, but his implicació in mental retardation to (m has not been tested. In the case of families affected by the syndrome Lenz has been identified mutaci6n responsible gene PQBP 1, located in Xp 11.23. This will expand both the heterogeneity alelica this gene is responsible for other syndromes and mental retardation inespecífico as heterogeneity genica the syndrome of Lenz, as the third locus associated with this disease. analysis of the case of sporadic syndrome Coffin-Lowry has identified an insertion of an element LINE L 1 defectivo in the gene RPS6KA3 as the cause of the molecular pathology by the patient. Insertion has occurred near Site giver of intrón 3, causing the skipping of exon 4, 10 involved a shift in the pattern of reading and the emergence of a premature stop codon, obteniéndose an incomplete protein.

Author: GONZÁLEZ CABO MARÍA PILAR.
Year: 2005.
University: VALENCIA [www.uv.es].
Place of defense: INSTITUTO DE BIOMEDICINA DE VALENCIA.
Place of preparation: INSTITUTO DE BIOMEDICINA DE VALENCIA.

Summary: The Deficit frataxina is the leading cause of the Friedreich ataxia, a neurodegenerative autos6mica recessive disease. The role of frataxina still not known. In this paper we show that Yfh1p, ortólogo of frataxina Saccharomyces cerevisiae, physically interacts with succinate dehydrogenase, specifically with the subunits Sdh1 py Sdh2p, in the transport chain mail mitochondrial yeast, and also with the subunits ETF (Ly ETFj: the flavoproteina transferidora electron interaction synthetic geneticos Experiments have confirmed a functional relationship between the gene YFH1 and genes of succinate dehydrogenase SDH1 and SDH2 We have also shown a physical interaction between frataxina human and succinate dehydrogenase subunit of the human, suggesting that frataxina has a role in the transport chain mail mitochondrial in humans. Therefore, we suggest a direct involvement of the cadenarespiratoria in the pathogenesis of the Friedreich ataxia, which suggest they may be considered as a disease OXPHOS.Desde discovery the frataxina and localizacipn like molecule of the mitochondrial matrix, of Friedreich ataxia has become the prototype of mitochondrial disease caused by a gene nuclear However, it is not the only ataxia which can be seen as mitochondrial. another example anemia gene counterpart ABC7 in Caenorhabditis efegans and then generaci6n a transitional mutant, which presents the following phenotype. embryonic lethality (Amb), stunting (Gro), reduction in egg-laying (Egi), and altered bowel increase in longevity. phenotype This is similar to other phenotypes associated with transient mutant gene related to the biogenesis of clusters Fe-S in yeast.

Author: López Nieva María del Pilar.
Year: 2005.
University: AUTÓNOMA DE MADRID [www.uam.es].
Place of defense: Facultad de Ciencias.
Place of preparation: Facultad de ciencias.

Summary: Lymphomas tímicos mouse induced by gamma radiation are a class of relatively heterogeneous lymphomas linfoblásticos type T formed by immature thymocytes (usually double negative (DN) or double positive (DP)). The obvious difficulties of working with human samples are desirable development of animal models, especially when it comes to identifying susceptibility genes minors. The analysis of a large collection of this type of lymphoma induced in susceptible strains of mice (C57BL/6J and BALB / cJ) has enabled us to identify new disturbances in several major susceptibility genes, as c-Myc, Notch and p21 to be on - expressed in practically all the same. Using strains consómicas and strains recombinant congénicas created between a strain highly susceptible (C57BL/6J), and other highly resistant (SPRET or SEG / Pas), we also identified two regions contain genes candidates under susceptibility (some character modifier) Chromosome 16 (Tlyr2) and 19 (Tlyr1). The genes coding for DNA-PKcs and a ligand system PD-1/PD-L1 could be good candidates in these regions.

Author: ANTONELL BOIXADER ANNA.
Year: 2005.
University: POMPEU FABRA [www.upf.edu].
Place of defense: DEPARTAMENTO DE CIENCIAS EXPERIMENTALES Y DE LA SALUD.
Place of preparation: DEPARTAMENTO DE CIENCIAS EXPERIMENTALES Y DE LA SALUD.

Summary: This paper presents molecular evolution and functional study of genes located in the segmental duplications in the region 7q11.23, has been implicated in the syndrome Williams-Beuren (SWB). Each of these consists of three overlapping blocks called A, B and C. It has been dated the emergence of these duplications in the past 25 million years of evolution and characterized in detail the region 7q11.23 human and ortólogas in other primates (chimpanzé, gorilla, orangutan and macaque). Each block has evolved independently, with Block B doubled exclusively in humans. In addition we propose an evolutionary model with specific rearrangements (mostly investment) and generation mechanisms. Alu sequences were detected in all ends of the blocks of segmental duplications, suggesting that phenomena of homologous recombination between these non-allelic have mediated the generation and expansion of local duplication. The extraordinary rate of evolutionary change in this region, extrapolates to other regions of the genome rich segmental duplications ago that there is a significant genomic variation among species of primates hominids, which may be functionally relevant and predispose to disease. Correlations clínico-moleculares in patients with SWB have identified the haploinsuficiencia by NCF1, located in a gene duplication and variable delecionado in patients, it is a protective factor for hypertension. It has proposed a model to explain this association pathogenic, implying oxidase NAD (P) H and oxidative stress. The haploinsuficiencia for the elastin gene present in all patients with SWB is known to lead to vascular stenosis i predisposes hypertension, and together with non-deletion of the gene NCF1 and therefore a normal ability to generate oxidative stress, makes patients with hypertension develop much more likely that if they deletion of the gene NCF1. It has also been suggested that new therapeutic strategies could be used. Finally, it has been partially characterized the role of GTF2lRD2, located in another gene duplication GTF2lRD2 interact with other transcription factors linked, has a location subcel.lular variable and does not bind to DNA. These results contribute to better understanding of the mechanisms of pathogenicity and mutacionales SWB.

Author: GÓMEZ ABAD CRISTINA ISABEL.
Year: 2005.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE CC. QUÍMICAS.
Place of preparation: FACULTAD DE CIENCIAS QUÍMICAS.

Summary: Lafora disease is a Epilepsy Mioclónica Progressive starting occurs during adolescence, and is accompanied by a progressive neurological deterioration of rapid evolution towards a terminal vegetative state. Patients usually die within a range that varies between 5 and 10 years after the onset of the disease. The hallmark of the disease is the presence of intracellular PAS-positivos deposit spread. We have described two genes responsible for disease: EPM2A and EPM2B. In this work we analyzed clinically and molecularly a total of 104 patients diagnosed with Lafora disease, belonging to 82 families. The mutated gene is found most frequently in our series of patients is EPM2A (67.1% of households). EPM2B is mutated in 30.5% of households. A 2.4% of the families have not been detected mutations in either of these two genes. In EPM2A we have identified 34 mutations different, 8 of which are new. Analysis of haplotypes associated with the most common mutation in EPM2A, R241X, indicates that the origin of this mutation is due to a founder effect as of recurrence. In EPM2B we have identified 18 mutations different, 12 of which are new. Analysis of haplotypes associated with the most frequent mutations in EPM2B indicates that the origin of the mutation P69A is due to a founder effect as of recurrence, whereas the mutation C26S is due to the existence of a founder effect. It has also carried out a comparative study between genotype and phenotype. The various clinical variables discussed in the comparison of the phenotypes EPM2A and EPM2B (age of onset of the deteriorating engine, age of death and years of disease progression) indicate that although mutations in both genes produce the same phenotype, the period of evolution it is longer in patients with mutations in EPM2B. The existence of families diagnosed with Lafora disease confirmed by biopsy without mutations in EPM2MA nor EPM2B, imply the existence of at least a third gene involved in Lafora disease.

Author: SAN PEDRO GARCÍA JOSÉ IGNACIO.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: HOSPITAL DE CRUCES.
Place of preparation: UNIVERSIDAD DEL PAIS VASCO.

Summary: The type 1 diabetes is an autoimmune disease in which takes place destruction of the pancreatic beta cell mediated by T lymphocytes Celiac disease, for its part, is an autoimmune disorder caused by an intolerance to gluten diet. Both are developed in genetically susceptible individuals. The region of HLA class II, on chromosome 6, has been proposed as the principal involved in genetic susceptibility to these two diseases, with HLA-DR3.DQ2 and HLA-DR4.DQ8, the major determinants of risk. In recent years, it has been suggested the existence of another region susceptiblidad for these two autoimmune diseases, the locus VDR (vitamin D receptor) on chromosome 12. One of the main functions of vitamin D is to act as a modulator of the immune system, exercising its main biological activity via its nuclear receptor (VDR), which acts as a transcription factor nuclear other genes. The partnership between allelic variants of the receptor gene of vitamin D and autoimmune diseases has been described in numerous works, we have studied different polymorphisms in the VDR locus on chromosome 12q12-14, with the aim of studying possible these association with type 1 diabetes and / or celiac disease in our population, as well as whether the same alleles were associated with both diseases. To perform this work techniques RFLP and allelic discrimination through probes TaqMan MGB. The results show, on the one hand, a statistically significant association between the haplotype fBAt and diabetes mellitus type 1, and secondly, an association, also statistically significant between genotype and ff celiac disease. In the light of these results we conclude that the gene polymorphisms of the vitamin D receptor are markers of susceptibility to type 1 diabetes mellitus and celiac disease. However, there is a heterogeneous population, but also in various pathologies within the same population. Because of this heterogeneity is not clear whether the VDR locus is the primary determinant etiological if it is a marker linked to the true susceptibility gene.

Author: SABATER LLEAL MARIA.
Year: 2005.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAT DE BIOLOGÍA.
Place of preparation: FACULTAT DE BIOLOGÍA - UNIVERSITAT DE BARCELONA.

Author: PAISÁN RUIZ CORO.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: E.U. ENFERMERÍA DE DONOSTÍA.
Place of preparation: HOSPITAL DONOSTIA/LAB. NEUROGENETICS (NIA/NIH).

Author: ALVAREZ ALVAREZ MAITE.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGÍA.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. There are some well-established environmental risk factors (gender, age, family history of dementia, etc.) and genetic (PDB PS1, PS2 and APOE), but still a lot of unknown / s cause / s that can cause this disease. On the other hand, a pre-EA is the Mild Cognitive Impairment (DCL). In this work we analyzed potential genetic markers located in the genes ESRalfa, ESRbeta, TNFbeta IDE, HTR-6 and CYP46A1 to determine their possible involvement in the EA (n = 246) and / or DCL (n = 156) as factors risk protection. Markers in the genes ESRalfa, TNFbeta, HTR-6 and CYP46A1 seem to show some association with the EA Or DCL, an association that mostly becomes apparent when the sample of patients was stratified on the basis of gender and / or presence / absence of APOE allele * 4.

Author: MARTÍN PAGOLA AINHOA.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: HOSPITAL DE CRUCES.
Place of preparation: HOSPITAL DE CRUCES.

Summary: Celiac disease (CD) is an autoimmune disorder caused by intolerance to gluten diet that develops in genetically susceptible individuals. The HLA region on chromosome 6 has been proposed as the principal involved in the susceptibility to the disease (specifically genes HLA class II DQ and DR). Thus, more than 90% of patients celíacos presented the allele DQ2, while a minority introduced allele DQ8. In recent years, it has been suggested the existence of a second susceptibility locus in the HLA region, near the HLA-B gene, which could have an independent effect on the class II genes. One of the candidate genes located in this region is the gene MICA (MHC class I Chain-realted A gene). This gene encodes a protein that is expressed in terms of stress in the gastrointestinal tissue and active cells of the immune system. The objective of this study is to determine the involvement of MICa in celiac disease. The results of this study show an association of a genetic polymorphism of the gene MICA CD, but is due to the linkage disequilibrium with HLA class II genes. Moreover, from the functional point of view, there seems to be an implication of MICA in the beginning of the innate immune response that develops in the intestine of patients celíacos, as a direct result of exposure to gluten of the intestinal mucosa, while does not appear to have an important role in the immune response that takes place in the advanced stages of celiac disease, where there is an intestinal lesion.

Author: PEDROLA VIDAL LAIA.
Year: 2006.
University: VALENCIA [www.uv.es].
Place of defense: FACULTAD DE MEDICINA DE LA UNIVERSITAT DE VALÈNCIA.
Place of preparation: FACULTAD DE CIENCIAS BIOLÓGICAS - UNIVERSITAT DE VALÈNCIA.

Summary: The disease Charcot-Marie- Tooth (CMT) is the most common neuropathy sensitivo-motora hereditary and is a very heterogeneous group of diseases both clinically and genetically. There are two ways depending on the topography of the primary lesion in the peripheral nerve: CMT demyelinating or type 1 and CMT axonal or type 2. It is now twenty-one described over and over forty gene loci associated with CMT, being most responsible for demyelinating forms. The disease Charcot-Marie- Tooth is characterized by progressive weakness and muscle atrophy in the limbs. Patients have to walk defects, feet cavos and hand grip. The age of onset of the disease is usually on the first or second decade of life. Charcot-Marie- Tooth type 4A (CMT4A) is a severe clinical form of CMT axonal with autosomal recessive inheritance, associated with disfonía. In 2001, our group isolated and characterized the gene responsible for the disease, GDAP1 (-ganglioside-induced differentiation-associated protein 1 ') located on chromosome 8q21. After characterization of the gene, we are studying GDAP1 in rare in patients who had been diagnosed and disfonía axonal neuropathy. In fourteen cases that we investigate and find a neutral polymorphism described above (S169S in eight chromosomes polimorficos of 28 chromosomes total) and two polymorphisms not described (L28L on a chromosome and R225R also in a chromosome of the 28 total). Given the frequent high of 51695 in our series calculate allelic frequencies of this (T and G = 51.3% = 48.6%). In addition there are two pathological changes in homozigosis and also described earlier, Q163X two chromosomes and S194X in six chromosomes. The three patients in our series showed that the mutation S194X as described in a Spanish family, were of Moroccan origin. We conducted an analysis of haplotypes for studying the origin of the chromosomes carrying the mutation and concluded that the mutation S194X has the same origin in individuals espaiioles and individuals Moroccan. To investigate the cellular origin of the pathogenesis studied the expression of GDAP1 in several neuronal and non-neuronal tissues of adult rats, as well as in cells 5chwann rat in different growing conditions. Note that GDAP1 is expressed predominantly in neuronal cells, suggesting that CMT4A is, in fact, an axonal neuropathy. Furthermore, we confirmed the expression of GDAP1 in various types of nerve cells and neurons in the olfactory bulb, hippocampus and cerebellum Purkinje cells. Note also expression in motor neurons of the spinal cord and sensory neurons in the dorsal root ganglion of the (DRGS), as is expected in a neuropathy axonal sensitivo-motora. The study of the subcellular localization of the protein determines that GDAP1 is located in mitochondrial membranes. AI to analyze the pattern of expression of GDAP1 define GDAP1 as a protein involved in the dinámic mitochondrial, inducing processes of fission. Mutations -missense "found in GDAP1 are expressed in mitochondria correctly by 10 that the molecular mechanism underlying the disease must be another, perhaps GDAP1 have other functions besides inducing mitochondrial fission or simply pequeiias differences in morphology trigger big effects in the balance of fusion and fission. Between these mutations exists one exception, the de novo mutation dominant T157P that when sobreexpresada produces mostly a morphology of mitochondria added. addition, the sobreexpresar protein without transmembrane domains to simulate mutations -nonsense II ( these mutations always truncated protein prior to the transmembrane domain) there is a relocation of the protein. Anyway, a defect in the function of GDAP1 leads to serious consequences in the nervous system, probably because mainly neurons have a high energy requirement it aportad 8 or gra 43b n measured by mitochondria. also confirm that the transmembrane domain further if necessary is sufficient to locate GDAP1 correctly. Lastly, we analyze whether GDAP1 was able to act as the other enzymes GSTs conjungando the glutathione with a standard chemical compound (CDNB) and note that at least in these test conditions, GDAP1 has no GST activity

Author: MARÍN GARCÍA PABLO.
Year: 2006.
University: VALENCIA [www.uv.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGÍA.
Place of preparation: FUNDACIÓN VALENCIANA DE INVESTIGACIONES BIOMÉDICAS/INSTITUTO DE INVESTIGACIONES CITOLÓGICAS.

Summary: Hypertension is a leading cause of cardiovascular morbidity and mortality of man. The implication of hypertension in the development of diseases of the cardiovascular system and kidney in each individual are the result of complex intereacciones between genetic factors and environmental conditions. This interaction not only genes can determine the answer to the blood pressure, but also the susceptibility of the target organ (heart, blood vessels, rilion etc.). Agents stressful com high blood pressure. This thesis assesses the possible link between several of the genetic polymorphisms of the major components of Renina Angiotensin Aldosterone System (SRAA) and the organic damage in hypertensive patients (as measured by the presence of microalbuminuria). It conducted a survey of several of the association between polymorphisms of genes of SRAA, and the prevalence and levels of microalbuminuria through a cohort study cross while entry into the study and other developments to 3 years. Of the studied polymorphisms (including the ACE I / D AGT c.-6G> A AGT p.M235T, AGT p.T174M, AGTR1 c.573C> Ty AGTR1 c.1166A> C), the cross-sectional study only c.573C> T seems to have any effect on the basal levels d microalbuminuria taking the TT allele the lowest levels of microalbuminuria. The longitudinal study has been that individuals with genotype AGT c.-6 M have an increased resistance to cuts microalbuminuria and this effect is independent of the reduction in blood pressure, and the ACE DD genotype has a positive correlation between the variation in PAS and the variation of microalbuminuria.

Author: Pérez Cadahía Beatriz.
Year: 2006.
University: A CORUÑA [www.udc.es].
Place of defense: Facultad de Ciencias.
Place of preparation: Facultad de Ciencias.

Summary: On November 19, 2002 the oil tanker Prestige broke his helmet to 130 nautical miles from the Galician coast spilling about 40,000 tons of fuel oil. Over the following weeks 22000 more arrived at the coast in the form of three oil slicks. The accident resulted in widespread shock because of the importance and richness of the eco-ary Galicia. A large number of people were mobilized to assist in the task of recovery of the affected areas and wildlife, positioning itself as part of a population exposed and potentially affected by the effects of fuel oil. In this paper we have analyzed these effects in a population of 240 individuals: 60 volunteers (exposed 5 days) 60 workers to collect fuel (4 months) 60 workers employed hidrolimpiadoras (3 months) and 60 controls. The exposure levels were determined through the analysis of volatile organic compounds environmental (VOCs) and heavy metals present in blood. It was used as biomarkers of genotoxic effect at the trial of the comet, the micronucleus test and exchanges between sister chromatids, and level endrocrino plasma levels of prolactin and cortisol, taking into account the possible influence of individual factors fisológicos, habits consumption and genotypic on susceptibility to the harm caused by exposure. After the analysis have been observed significant levels of VOCs in the air samples, and the concentrations of heavy metals in the blood reflect the existence of an internal exposure. It has achieved an increase in levels of DNA damage in the exposed individuals. As for endocrine toxicity, the results suggest that the mixture of xenobiotics in the oil from the Prestige induces alterations in the hormonal status, which can be seen as an endocrine disrupter. Moreover, the results show that the levels of damage are influenced by gender, age and consumption of snuff, while the use of protective equipment during the cleanup had not proved relevant. The analyzed genetic polymorphisms in metabolic enzymes and DNA repair appear to exert considerable influence over the biomarkers effects analyzed. The selected parameters have proved to be good indicators of the processes of toxicity associated with exposure to fuel oil from the Prestige.

Author: OTAEGUI BICHOT DAVID.
Year: 2006.
University: PAÍS VASCO [www.ehu.es].
Place of defense: ESCUELA DE ENFERMERÍA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGÍA - UPV/EHU.

Summary: INTRODUCTION This paper attempts to draw closer to the genetic susceptibility factors that influence the risk to suffer from multiple sclerosis (MS) or in the evolution of it. This would have used two methods of approximation. First were studied SNPS at 8 gene proposed in the literature as partners with MS and in the system of haplogrupos mitochondrial DNA. The second approach has been to study the patterns of gene expression in nodules Linfáticos a mouse model SEA. In mice is coughing has led to an SEA made on outbreaks and has built a model of the longitudinal disease with tissue extractions in 12 different points. In these tissues has been studied the expression of 18000 transcribed by RNA arrays. To corroborate the findings in this study have been studied some of the proposed RNA genes obtained from patients. RESULTS haplogrupos mitochondrial and proposed SNPs in genes CD24, APOE and PD1.3 unrelated to MS. In our data do appear related to the disease studied changes in gene CCR5, TLR-4, UCP-2 and SYN III. In the study of speech in SEA has been characterized transcriptional signatures of nonspecific immune response against the adjuvant. It proposes a model that looks like the transcriptional signatures of immune cells migrate to the lymph node SNC. It is proposed that the genes of casein, lactoalbumina and Expri play a protective role in the outbreak in the EAE model. It is proposed that the kappa casein plays a role in the body's response against the outbreak in humans.

Author: URREIZTI FREXEDAS ROSER.
Year: 2006.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: FACULTAD DE BIOLOGÍA (UNIVERSIDAD DE BARCELONA).

Summary: The aim of this thesis has been studying molecular changes in plasma two pathologies associated with this metabolite. On the one hand, the disease monogéncia homocistinuria (Hcu) classical [deficiency in the enzyme Cistationina beta-sintasa (CBS)]. Moreover the study of association of candidate genes for the metabolism of homocysteine (Hcy) lahiperhoimocisteinemia and ischemic heart disease (IAC). The study molecular the Hcu in patients of the Iberian Peninsula and Latin America has characterized the 96% of the alleles grounds. We have found a high prevalence of allele p.T191M therefore on the Peninsula and in Colombia. Through the study of haplotypes have been identified multiple origin for this allele. To check patogeneicidad of mutant alleles study functional 14 of the changes found that most mutated enzymes completely lose the changes found in the cohort study found that most mutated enzymes completely lost their enzymatic activity while only 3 preserve values of activity more than 10, including the enzyme mutated p.R548Q retains 60% of the activity and correct a pattern of activation, suggesting that this change is a polymorphism rather than a pathogenic mutation. In partnership with studying candidate genes we found that the allele c.66 G gene MSR is significantly associated with an increased relative risk (RR) to suffer IAC 1.76. Ace or rather, the haplotype present in the CBS gene is significantly associated with an increased RR of 2.16. The polymorphisms in the gene MTHFR are the only significantly associated with the levels of Hcy.