CLINICAL GENETICS

Author: RODRIGUEZ-REVENGA BODI LAIA.
Year: 2003.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE BIOLOGҍA-UNIVERSIDAD DE BARCELONA.

Summary: The sÃÂndrome Williams (SW) is a disorder of development characterized by facial features caracterÃÂsticos, with a particular mental retardation and ÃÂ º nico cognitive profile and personality, hypercalcemia and child anomalÃÂas in the connective tissue which include arteriopatÃÂas, mÃÂ ¡s caracterÃÂsticas is stenosis supravalvular aÃÂ ³ rtica (SVAS). It is therefore a disorder multsistÃÂ © mico that occurs with an incidence of 1/20.000 live births and it gives them evenly between men and women. Although mayorÃÂa cases of 3W are esporÃÂ ¡dicos have documented several families in which the sÃÂndrome is presented using a patrÃÂ ³ n inheritance autosÃÂ ³ mico dominant. The alteraciÃÂ ³ n molecular involved in the SW is a deleciÃÂ ³ n hemicigota approximately 1.5 Mb on chromosome 7 that specifically affects regiÃÂ ³ n 7q11.23. It is therefore one of the sÃÂndromes gene contiguous since the deleciÃÂ ³ n affects several genes located on the regiÃÂ charges involved. The causal mechanism in the SW appears to be the haploinsufiencia gÃÂ © nica some of the genes that are found in regiÃÂ ³ n delecionada. Anyway, there are discarded as other mechanisms: 1-That the deleciÃÂ charges put to the discovery a mutaciÃÂ charges in the other allele recessive gene. 2-That the deleciÃÂ charges may affect undergoing gene imprinting, namely that normally are expressed from one of the alleles, depending on its parental origin. 3 - The deleciÃÂ charges of any of these genes affect the expresiÃÂ ³ No other located in another area of the genome. Up to now, have been described 20 genes with locus in this regiÃÂ charges, one of which is the coding for proteÃÂna of elastin (ELN). This is the ÃÂ fourth single gene with which it has been possible to establish a correlaciÃÂ ³ n genotipo - fenotipo since altered its sequence given caracterÃÂsticas demonstrations cardÃÂacas and vascular present in the SW. While the SW is the result of haploinsuficiencia gene ELN and other genes located nearby, mutations in this gene lead to the riots autosÃÂ ³ dominant monkeys distinct stenosis supravalvular aÃÂ ³ rtica (SVAS) and the loose skin. Studies genÃÂ © ticos using hibridaciÃÂ ³ n ins itu fluorescent (FISH) and anÃÂ ¡lysis of pÃÂ © rdidas of heterocigosidad with markers of regiÃÂ ³ n 7q11.23 show the pÃÂ © rdidad material genÃÂ © tico and enable diagnÃÂ ³ lstico of SW. These studies allow the narrow Gross deletions, establish a correlaciÃÂ ³ n genotipo - fenotipo study the origin and parental its repercusiÃÂ charges and the phenotype. The use jointly tÃÂ © cnicas molecular and FISH not sÃÂ ³ permits characterize different deletions presenting patients. This paper tries to deepen the knowledge of SW travÃÂ © s of caracterizaciÃÂ ³ n of patients suffering that the Service GenÃÂ © tica Hospital ClÃÂnico has collected in ÃÂ eighth past seven aÃÂ ± os.Igualmente, tambiÃÂ © n intends to conduct a study mutacional gene ELN in those patients who had not been demonstrated deleciÃÂ charges in the same gene but fenotÃÂpicamente presented algÃÂ º n type afectaciÃÂ ³ n cardiovascular, and molecularly characterized the sÃÂndrome of Cutis Laxa. We analyzed 200 patients with suspected clÃÂnica SW and through some of the two tÃÂ © cnicas used, it has been revealed a hemicigosidad of regiÃÂ ³ n crÃÂtica in 70 cases. This represents that sÃÂ ³ what to 35% of the cases received were suspected clÃÂnica SW actually submit the delecciÃÂ ³ n. In 5 of these, the molecular study has not been informative while in the 65 remaining, it has been able to study and determine the parental origin of the deleciÃÂ ³ n. It has conducted the study mutacional ELN gene in a total of 28 individuals who had their phenotype in any afectaciÃÂ ³ No cardiac or hallmarks of Cutis Laxa. This study 8 has allow 442 tido identify a total of eleven changes which three already habÃÂan been described previously. Nine are polymorphisms and the other two are missense changes in exons 22 and 26. Among the polymorphisms, sies are intrÃÂ ³ nicos and three are expressed to be exÃÂ ³ nicos. Respect for the Cutis Laxa, in the literature sÃÂ ³ what existÃÂan 3 cases des critos where mutaciÃÂ ³ n cauante mentioned. This study tambiÃÂ © n has identified a fourth mutaciÃÂ charges related to this disorder. Besides the implications cientÃÂficas, this work investigaciÃÂ ³ n demonstrates once mÃÂ ¡s usefulness of anÃÂ ¡lisis genÃÂ © tion as a tool diagnÃÂ ³ sightseeing for this sÃÂndrome.

Author: ROS MACHO-QUEVEDO RAQUEL.
Year: 2003.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: BANCO DE TEJIDOS PARA INVESTIGACIÓN NEUROLÓGICA.F.MEDICINA.UCM.

Summary: This work has been the search for potential genetic lesions responsible for taupatías, diseases constituting after Alzheimer's disease and Parkinson's the most important group of emerging diseases neurodegenerativas.En particular, we have focused on the study of progressive supranuclear palsy both sporadic as family and frontotemporales dementias. Our analysis has allowed in the case of the PSP:. The localization of a locus in a large Spanish family with pathological confirmation in the testing, on chromosome 1 in the region 1q31. . Identifying risk factors, both inthe sporadic cases as relatives of polymorphisms in genes TAU, STH And PARK2. . A new mutation in the gene TAU in a family with a clinical diagnosis and patolófico PSP. For other non-Alzheimer degenerative dementias, the analysis of gene TAU in the 33 cases studied has enabled us to the identification of three mutations in the gene TAU, two already reported in two patients with frontotemporal dementia, and a new, in a case of aphasia Primary Progressive.

Author: QUINTEIRO GARCÍA CELSA.
Year: 2004.
University: SANTIAGO DE COMPOSTELA [www.usc.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: UNIVERSIDAD DE SANTIAGO DE COMPOSTELA.

Summary: The low height affects the 2 or 3% of the general population and less than 1% identifies the cause of the disruption of growth, its diagnosis is taIla low idiopathic (BITs), and many cases are probably caused by defects in subtle elements involved in the response to GH. The study of the DNA sequence has increased awareness of other causes of hipocrecimiento as DCHH, the deficit isolated GH deficiency syndrome Laron and insensitivity syndrome partial GH. The foundations of molecular alterations that IIevan to taIla low have desarroIlado by location and characterization of the genes encoding proteins involved in growth. Objectives: 1.Estudiar in the group of GH deficiency associated with deficiency of other pituitary hormones genes PROPI and POUIFI, in the group of patients with isolated GH deficiency, the gene GHl yen cases of insensitivity to GH gene RXQFLO DQG PDUFK and in patients with discondrosteosis gene SHOX. 2. In patients with TBI analyze genes and GHI RXQFLO DQG PDUFK trying to raise the specter of mutacional genes GHI and RXQFLO DQG PDUFK. 3. Consider fTecuenciade polymorphisms of these genes by comparing different diagnostic groups among themselves, and in some cases with population control. Conclusions: l. Confirmation of the genetic basis of impaired growth requires the demonstration of mutations in the genes involved, so we have to point the techniques of molecular analysis of genes PROPl, POUIFl, GHl, RXQFLO DQG PDUFK And SHOX by sequencing complete the same. 2. It was found in 14 patients (28% of cases) with DCHH, mutations in PROPl and POUIFl. The mutations are found most often seen in all published series. 3. In GHl we have identified 31 changes nucleotídicos of these 20 have not been previously described. The sequence coding are 9 mutations. The gene GHl presents a high variability with two "hotspots" areas, one in the region 5 'and the other in the intrón IV. Some of these variants can be caused by a conversion mechanism, a result of the structure multigénica dellocus GH. The broader spectrum of variants was found in patients with taIla low family and in no case were found large deletions. 4. The gene RXQFLO DQG PDUFK find 4 mutations in 5 patients, describing for the first time a mutation in exon 2 of this gene (M 1L) And demonstrating that the analysis of the coding region of the mature protein is insufficient to identify all mutations. It was found in the one patient with syndrome Laron. Mutations in RXQFLO DQG PDUFK can play an important role in the pathogenesis of low stature when presented as part of other syndromes, as in Costello syndrome. 5. We found a 43% of cases with haploinsuficiencia gene SHOX, half of them for loss of allele and half by point mutations. It has been described three new mutations, one in the regiól1 OHR, which were never found. The analysis by sequencing of exon 5b has revealed a single nucleotide polymorphism, useful in establishing whether or not the deletion of an ale it. 6. Patients with TBI were identified mutations in the genes in heterocigosis GHI and RXQFLO DQG PDUFK, none of nava, which supported the tabling of the family table. These findings are consistent with other work, where tables are associated with milder mutations in a single ale it, whereas in the more severe are both affected. 7. The development of knowledge enables molecular diagnosis increasingly precise alterations 8 of crec 2a2 imiento, not only in cases of hormone deficiencies, but in clarifying etiology of this "catch -" which is the BIT and consequently lead the correct treatment for those individuals who feasible, and to conduct a proper genetic counseling.

Author: FÉRNANDEZ GARCÍA RAQUEL M..
Year: 2004.
University: SEVILLA [www.us.es].
Place of defense: HOSPITALES UNIVERSITARIO VIRGEN DEL ROCIO.
Place of preparation: UNIDAD CLÍNICA DE GENÉTICA Y REPRODUCCIÓN, HHUU VIRGEN DEL ROCIO.

Summary: A. HIPOTESIS OF WORK: Functional Studies have shown that the proto-oncogén RET associates, po mechanisms contrary both to the emergence of Hirschsprung's disease (HSCR) and medullary thyroid cancer (MfC). So, today we know that germ RET mutations leading to a gain of receptor function originate familiar forms of MfC (syndromes MEN 2), while other mutations that cause a loss of function are causing HSCR. Our group has significant evidence of the association of variant A45A, located in exon 2 of RET with the phenotype HSCR. All results previously published by our group suggest a locus associated with ancestral haplotypes containing A45A, located in 5 'on this option and an interval 0-20Kb (region that corresponds to intrón 1de RET) . The main objective of this thesis project is the identification and molecular characterization of this susceptibility locus for HSCR. Specifically, this locus could be associated with a domain involved in regulating the expression of RET. Achieving these objectives and contribute to the elucidation of the genetic basis of this disease. Also, given the polygenic nature of HSCR, we wanted to develop a systematic evaluation of other genes candidates, in order to identify factors associated with susceptibility to emerge. Moreover, knowledge on the etiology of sporadic medullary thyroid cancer is quite low. However, since activating mutations in RET are responsible for the familiar forms of MfC and that the mutation somatic M918T was found in lma significant proportion of sporadic tumors, this gene becomes the primary candidate gene for susceptibility to as forms MfC sporadic. This hypothesis is supported by the fact that the starting point of this study, the only factor described susceptibility to sporadic MTC in a number of cases was the German polymorphism S836S, located in exon 14 of RET. Therefore, we have the possibility of changing sequence of the genes involved in the cascade of metabolic RET, such as the receiver, their ligands or coreceptores, might have a role in the pathogenesis of ERM. Based on this idea, we have initiated a search for genetic susceptibility factors for this disease in these candidate genes. B TARGETS RAISED l. Identification and molecular characterization of a new locus HSCR linked to the haplotypes containing the gene polymorphism A45A of RET. 2. Analysis of mutations and polymorphisms in genes other candidates for HSCR. Evaluation of his involvement in the emergence of enfemledad. 3. Searching for genetic susceptibility factors for MfC sporadic in candidate genes for this disease. L. C CONCLUSIONS It has marked a new mutation in the proto-oncogén RET, c.2304G lower T (E768D) in a patient with medullary thyroid cancer. The absence of other clinical features or a family history of MEN 2A suggests that this mutation is associated with the phenotype FMTC. 2. The phenomenon of association variants -193C lower Gy 537Tmenor C gene GFRAl to sporadic forms of MfC in the German population is not reproducible in the Spanish population. None of the variants of genes GFRAl-3 appear to be factors in susceptibility to the development of disease in our population. 3. Both the analysis mutacional as evaluating polymorphisms in genes GFRAl, GFRA2, GFRA3 and GFRA4 as susceptibility factors for HSCR, discard these genes as being responsible in the pathogenesis of the disease. 4. We have identified two variants of sequence in proto-oncogén RET sobre in our series MfC, S836S and IVSl-126G lower T. These findings sug 8 ieren the 4c1 existence of a susceptibility locus for low penetrance ERM linked to both alternatives, which could occur in the direction 5 '. 5. We have identified a specific proto-oncogén RET allele, associated with sporadic forms of Hirschsprung's disease. The functional in vitro studies suggest that the allele causes a decrease in the level of gene expression level RET. These results argue that this allele, probably in conjunction with other factors susceptibility, is causing the emergence of HSCR sporadic. 6. The mutation C620S of proto-oncogén RET is the cause of the table MEN 2A, but not the disease HSCR in a family where cosegregan both phenotypes, both ruled by the dual effect proposed by other authors for this mutation.

Author: CORNO CAPARROS ANDRES.
Year: 2004.
University: MIGUEL HERNÁNDEZ DE ELCHE [www.umh.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: ANALISIS GENETICOS ANCOR.

Summary: Colorectal cancer (CRC) is a very prevalent disease. It is associated with genetic factors, among others. The individual susceptibility to RACs may be due to variations in the ability to activate and detoxify endogenous and exogenous and repair the damage they cause in the DNA. Some polymorphisms in genes can lead to variations in activity detoxificadoras and remedial and thus increase the risk of individual padecerlo. Issues related to the frequency of null polymorphism in the gene detoxiviación GSTM1 and GSTT1, the frequency of polymorphism court MSp I (T6235C) and lle462Val 8C4889G) in the gene CYP1A1 metabolic activation and frequencies of polymorphism Ala677Val (C677T) in the gene MTHFR metabolism of folate involved in the mechanisms of synthesis and repair of DNA methylation. MATERIALS AND METHODS observational study of incident cases and controls, in Caucasians living in the same geographical area (Vega Baja Alicante). Sample cases: 93 patients with a confirmed diagnosis of colorectal adenocarcinoma (pathological) and controls, 117-patient with non-neoplastic disease (herniorrafias and colecistectomías). Qiagen kit was used to extract and purify DNA from whole blood. The null polymorphisms in GST; 1 and GSTT21 were analyzed using a multiplex, following the method described by Arand. The polymorphisms in the CYP1A1 were determined by the method described by Drakoulis 1994, amplification and cut with Msp I CYP1A1 * 2, and ASO CYP1A1 * 3 for the polymorphism A4889G. The polymorphism C677T in the gene MTHFR by the method of Frosst by PCr and subsequent digestion of amplified with Hinf.I. We reviewed the following variables: age, gender, weight, height, body mass index, alcohol intake habits, smoking, tumor location, estadiaje of Dukes and histological type of the tumor. In the analysis of results has been used a statistical model of linear regression, calculating odds ratio and value of P. There has been an individualized analysis of each variable versus risk of pathology and analysis of partnerships between genotypes and epidemiologic and clinical variables. RESULTS In our series was significantly associated with risk of CRC carriers of the polymorphisms: GSTM1 * 1 OR = 1.90 (95% CI 1.52-2.28) Pmenor 0.05, GSTT1 * 0 OR = 3.09 (95% CI 2.34-3.85) P less 0.05 and MTHFR * 2 OR = 3.08 (95% CI 1.81-4.36 = P less 0.05. null genotype in GSTM1 * 0 OR = 0.7 (95% CI 0.48-0.92) P less 0.05 was significantly associated with protection. was obtained significant value P less 0.05 in the distal location in relation to gender, being more common in men 64% vs. women 36%. analysis of the genotypes of risk according to age groups: 15-44 years, 45-64 and over 65 years were obtained values significant association with the risk yd eP in polymorphisms: GSTM1 * 1 OR = 1.57 (95% CI 1.45-1.69) P less 0,001, GSITT1 * 0 OR = 3.98 (95% CI 3.88 -4.1) P less 0,001 and MTHFR * 2 OR = 5.49 (95% CI 5.35-5.63) P less 0,001 in the age group older than 65 years. People with a higher risk are the carriers of the following combinations of polymorphisms, in the age group older than 65 years. GSTM1 * 1 + GSTT1 * 0 OR = 3.99 (95% CI 3.9-4.1) P less 0,001 GSTM1 * 1 + MTHFR * 2 OR = 5.49 (95% CI 5.3-5.6) P lower 0,001 GSTT1 * 0 + MTHFR * 2 OR = 7.17 (95% CI 7.02-7.3) P less 0,001 GSTM1 * 1 + GSTT1 * 0 + MTHFR * 2 OR = 13.9 (95% CI 13.8-14.0) P less 0,001 were also significant in the age group 45-64 years associations GSTT1 * 0 + MTHFR * 2 OR = 1.53 (95% CI 1.2-1.8) P less 0.01 and GSTM1 * 1 + GSTT1 * 0 + MTHFR * 2 OR = 2.98 (95% CI 2.8- 3.2) P less 0,001. CONCLUSIONS have been identified genetic factors significantly associated with risk fren 8 you to ade 667 nocarcinomas sporadic colorectal in our series. Their analysis can help identify risk groups and the elucidation of factors involved in colon cancer . in GSTM1 null The results are contrary to the assumption of risk heading partnership. our series of null genotype was significantly associated with protection and the savage is the genotype is associated with significant risk. polymorphisms in CYP1A1, CYP1A1 * 2 and * 3 are associated with reisgo but with no significant values. metilen tetrahidrofolato reductase activity smaller MTHFR * 2, confers an increased risk compared with CCR, in the studied population. association of two or more genotypes risk, in a way special GSTM1 * 1-GSTT1 * 0 and MTHFR * 2 confers a high risk especially in the age group of over 65 years, which raises the desirability to investigate the preventive potential of dietary supplements to foods rich in folate.

Author: GIMÉNEZ BACHS JOSÉ MIGUEL.
Year: 2004.
University: AUTÓNOMA DE MADRID [www.uam.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: INTRODUCTION The etiology of renal renal cell cancer (RCC) has been involved a number of factors, including genetic. Among them, altering the short arm of chromosome 3 is a very common. That location is the gene vhl, tumor suppressor gene, which is related to the von Hippel-Lindau disease, transmitted family. This gene may submit alterations in the CCR occasional, so that changes occur that prevent the proper execution of the suppressive function of the resulting protein. Objectives To determine the presence of mutations in the gene vhl in kidney tumor tissue of patients with renal carcinoma sporadic. Analyze the type and location of mutations found, as well as the change in the protein it produces and if it sits in key locations from the functional point of view. Moreover, the presence of mutations associated with prognostic factors such as tumor stage, type histopathology, nuclear grade, and so on. Analyzing the secondary structure of the mutated protein. SUBJECT, EQUIPMENT AND METHOD observational descriptive and analytical study on 86 patients diagnosed with RCC and treaties surgical mind in the Service of Urology University Hospital Complex Albacete, between August 2000 and May 2004. Samples were obtained from tumor tissue and surgical specimens of healthy kidney tissue to be utílizaron control. Of these samples were extracted for DNA amplification from each of the 3 exons that make up the gene vhl, using the PCR technique. The amplified product was subjected to automatic sequencing, with the aim of detecting mutations in the regions codíficantes gene. He also performed the characterization of the mutations found by analyzing changes in amino acid produced in the protein and a prediction of the secondary structure of the same. The dependent variable was considered the presence of mutations in the gene vhl, performed descriptive analysis with measures of central tendency and dispersion of each of the independent variables; bivariate analysis to study the association between two variables; and applied a multivariate regression model logistics to study the relationship between the independent variables analyzed and dependent. RESULTS The average age of patients was 63.1 years, with a sex ratio of 58 males (67.4%) and 28 women. Patients were radical surgery in 66.3% of cases and a 30.2% nephrectomy conservative parenchyma. The incidental finding of the tumor was the most frequent cause of consultation (52.3%). There were complications from surgery in 25.6% of patients, either at the time of íntervención surgery or post-operative. The tumor size was a 45.3% between 4 and 7 cm, and a 29.1% greater than 7cm. The most common type histopathology was clear cell with a 62.8% share, followed by papillary (14%) and cromófobo (10.4%). A 55.8% of cases the grade nuclear Fuhrman was 2 and the 23.2% was 3. A 59.2% of patients had a stadium pT1a or pT1 b diagnosis and only 4.7% were stage pT4. The evaluation of lymph node involvement was performed in 22 cases, of which 16 had adenopatías tumor. The 16.3% of the cases filed metastases in rr.omento the distance diagnosis. We detected a total of 20 mutations the gene vhl in kidney tumor tissue of 19 patients (22.1%), not being mutations in the control samples. The average age of patients with mutation was 74.2 years 8 and hal 9d8 laron mutations in a 17.8% women compared to a 24.1% in men. Mutations presented statistical association only with the histopathological subtype, so that the 78.9% happened in clear cell carcinomas. Some 45% of the mutations were found in exon 2, a 35% e11, a 5% for the 3 and the remainder in locating intrónica. The 65% of the mutations were isolated, a 30% and a 5% deletions insertions. 7 of the mutations exónicas rise to a truncated protein. Altogether it was felt that the 17 mutations exónicas, a 70.6% rise changes relevant to the function of the protein, either lead to a truncated protein, the physico-chemical characteristics of the amino acids mutated or by the degree of conservation of amino acids along the evolution, while the 41.2% generated significant changes in the secondary structure of the protein made according to the prediction. Of the 3 mutations intrónicas, 2 generated changes that could affect the function of the protein. In the multivariate analysis applied the only independent variable that remained in the model was the histological studies of the tumor, so the existence of mutations in the gene vhl is 8.33 times higher in the cell subtype clear than in the rest of the variants pathological. CONCLUSIONS The gene vhl introduced mutations in the renal cell carcinoma occasional, these being the most common subtype in clear cell. These mutations have no association with different parameters as clínico - patológicos stadium tumaral, size and nuclear grade. Mutations recorded mostly in key locations from the functional point of view, places conserved over evolution and where they are located binding domains of other proteins by exercising its function suppressor. Therefore, mutations of the gene vhl represent an event implicated in the génesís of kidney cancer, which helps your understanding and approach new weapons diagnostic and therapeutic approach for this clinical disease.

Author: CORRAL GUDINO LUIS.
Year: 2004.
University: SALAMANCA [www.usal.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Introduction Bone Paget's Disease (EOP) is a chronic disease of the skeleton and focal whose initial disturbance is located in osteoclasts. The cytokines IL-1 and IL-6 play an important role in bone remodeling, modulated osteoclast differentiation and activity, so that their study could provide data to the pathogenesis of the EOP. Objectives - Establishing the clinical features of EOP in a hotbed of high prevalence. - Describe the response to treatment in a historical cohort. - Assess the relationship between polymorphisms of IL1 and IL6 and the EOP. Materials and Methods We studied 211 patients (35% from the hotbed of high prevalence for the party judicial Vitigudino [Salamanca]). We got sample of peripheral blood of 126 of these patients for further study of DNA by PCR-RFLP. Was selected as a control group to 122 individuals without metabolic bone disease known. Results and Conclusions Patients belonging to the hotbed of high prevalence of Vitigudino have more severe clinical forms of EOP, most are diagnosed early and have a higher percentage of men than patients in the rest of the province of Salamanca. - The effectiveness of therapy with calcitonin is lower than that of any bisphosphonate and there is a trend towards a better response to treatment with the EOP nitrogenous bisphosphonates. - The presence of allele A2 polymorphism -511 C / T in the promoter region of the gene of IL-1B is associated with a better response to treatment with bisphosphonates. - We found no relationship between polymorphisms +3953 T / C in exon 5 of the gene of IL-1B, VNTR in intrón 2 of the gene IL1-RN, in the region 5Â'UTR of the gene IL-1 R1 and the -174 G / C in the promoter region of the gene for IL-6 and the EOP.

Author: CRUZ GONZALEZ IGNACIO.
Year: 2004.
University: SALAMANCA [www.usal.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The HIPERTENSIÓN ARTERIAL REFRACTORY (HTA-R) is defined as situations in which it is not possible to achieve the goal blood pressure in patients who have made changes in lifestyle and are taking the appropriate dosage of a drug therapy for 3 drugs including a diuretic. So far this entity has been addressed as a lack of compliance or malpractice, however part of this resistance could be determined at the genetic level studied in 50 patients HTA-R, 234 hypertensive controlled hypertension and 112 subjects without the genetic polymorphisms -786C higher T NOS3, 984G greater than T, 35G higher than C PPARG, 8473C greater than T PTGS2, 825C higher than T GNB, 1947G greater than A COMT, GSTM1, GSTT1, 313A greater than G GSTP1. We found differences between HTA-Re hypertensive checked the C allele of -786C higher than T NOS3 is more common in HTA-R with respect to the control (p = 0014 OR 2.32 (1.17-4.63)) the T allele of 825C higher than T GNB3 is associated with hypertension with regard to control subjects (p = 0016 OR 1.4 (1,04-1.91)), hypertension and controlled with respect to HTA-R (p = 0035 OR 0.6 (0.38-0.96), the null allele of GSTM increased susceptibility to develop HTA-R regarding controlled hypertension (p = 0025 OR 2029 (1.08-3.78)), and the presence of GSTT is linked with hypertension with respect to controls (p = 0040 OR = 1.68 (1021-2,77)) So there are differences in the distribution of genotypes of the genes selected in this study in patients with refractory hypertension, hypertension controlled and subject not with hypertension, suggesting that the origin of high blood pressure and its response to treatment are, at least in part, depend on the genetic level.

Author: ESTEBAN CARDEÑOSA EVA Ma..
Year: 2004.
University: VALLADOLID [www.uva.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FAC. MEDICINA.

Summary: It is estimated that approximately 5% of breast cancers are hereditary. Haste the time was described two genes high susceptibility to breast and ovarian cancer, called BRCA1 (Miki et al. 1994) and BRCA2 (Wooster et al. 1995). It has been described over 3000 mutations spread over the two susceptibility genes described (BIC). The carriers of a pathogenic mutation in one of them have a very high risk of developing the disease over their lives. The genetic analysis through molecular biology techniques that define mutations in both genes can identify families with breast or ovarian cancer are hereditary, posibilatando the implementation of protocols for monitoring and treatment for specific individuals, healthy or sick, those who detect a pathogenic mutation. These processes are very laborious, as it is the tracking of two major genes in which mutations have been described in all its exons. In most studies, the detection of mutations PROCEDURE is based on the use of techniques pre-rastreo (SSCP, DGGE, CSGE, PTT ...), and later studied by sequencing samples suspected of carrying a mutation (Easton et al. 1995). For these reasons, the results of genetic tests of BRCAs, on the other hand, casda again defendants, it takes several months to arrive. The main aim of the thesis is the detection of mutations in the genes BRCA1 and BRCA2 among families of Castile and Leon and the evaluation of their impact pathogenic, as well as the identification of families who carry these mutations pathogenic, which They can implement measures to prevent and tratamientoespecífico of breast and ovarian hereditary. To facilitate this search mutations aims to develop a new method of detecting mutations rapid and sensitive based on capillary electrophoresis on an automatic sequencer. It also wants to know whether the families without mutation in the genes NÂ Do BRCAs is present allele low penetrance c.1100delC gene CHEK2. It seleccionana 280 families castellano-leonesas with a family history and / or pesonal of breast cancer and ovarian cancer, contains sample of peripheral blood from them and then proceed to their analysis mutacional using different techniques. (TTP and analysis heterodúplex by CSGE). In addition it is set to develop a new method, the analysis Heterodúplex by Capillary Electrophoresis (AHEC), higher performance and greater sensitivity analysis that previously appointed. With the new method can be analyzed in two patients in a single career electroforética an hour and a half in duration. After análissi molecular in 280 selected families, have been found 101 mutations in two different genes analyzed, 30 of them are described for the first time on a global basis in our study. Venticuatro are pathogenic mutations, namely that relacionana with the onset of breast and ovarian cancer in those families. Two of them are large gene rearrangements representing the first cases described in Spanish population of this type of mutacioens in gernes BRCAs. We have identified 44 families unrelated presenting m utación pathogenic in one of the two high susceptibility genes, and thus breast cancer and ovarian there is hereditary. The highest rate of mutation was found in families with cases of breast cancer and ovarian cancer at the same time. Variant c.1100delC gene CHEK2 is absent from our sample population. Therefore, CHEK2 is not a gene for susceptibility to breast cancer in the study population. It dismisses thus tracing mutacional routine in our population moderado-alto risk for breast cancer and ovarian cancer. Failure to identify deleterious mutations in 8 of gene 3cc is high susceptibility to breast cancer, BRCA1 and BRCA2 suggested the existence of more genes high susceptibility to breast cancer hereditary, or the existence of an alternative model of inheritance (model polygenic) in a significant proportion of what we know as family breast cancer.

Author: BLANCO VICTOR MARTIN.
Year: 2004.
University: PABLO DE OLAVIDE [www.upo.es].
Place of defense: FACULTAD DE CIENCIAS EXPERIMENTALES.
Place of preparation: FACULTAD DE CIENCIAS EXPERIMENTALES.

Summary: We studied the effects of conjugated NH3/NH4 + pair (ammonia / ammonium) on volu-men cellular aqueous (VCA) and intracellular pH (pHi) cells in vitro neuroblastoma N1E-115 in. The VCA and pHi are measured simultaneously in cells isolated from changes in the fluorescence of the indicator BCECF, by incorporating it into the cells. For records used a technique microscopy and fluorescence cuanti-tativa developed validated in our laboratory. It proves that the transient exposure of the cells to solutions isosmóticas containing NH3/NH4 + (NH4Cl: 0,5-30 mM) produces, in addition to expected changes in the pHi, changes in the VCA, which distinguishes 4 phases: 1) a rapid rise; 2) a decrease in the volume regulator (DRVi), and after the elimination of pulse NH4Cl: 3) a rapid shrinkage, followed by 4) an increase in the volume regulator (ARVi). The occurrence of changes in cell volume before exposure to ammonium salts, but predicted for more than 80 years (HM Jacobs, 1940), had not been demonstrated so far. From the characterization of these changes, investigated the mechanisms underlying them. We conclude that a significant part of the initial increase in the VCA was de-be the intracellular accumulation of NH4 + and a hypothetical anion companion, not yet identified, it would be necessary to preserve the electroneutralidad macroscopic cell interior. The model is presented in the pathophysiologic correlate cerebral edema associated with hiperamonemias acute in humans, and is a useful tool for studying the pathogenic mechanisms of the latter.

Author: Camprubí Sánchez Cristina.
Year: 2004.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: Facultat de Ciències.
Place of preparation: Escola de Postgrau.

Author: GARCIA HOYOS MARIA.
Year: 2004.
University: AUTÓNOMA DE MADRID [www.uam.es].
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Author: SANTIAGO ALVAREZ JOSE LUIS.
Year: 2004.
University: SALAMANCA [www.usal.es].
Place of defense: FACULTAD DE BIOLOGIA.
Place of preparation: UNIVERSIDAD DE SALAMANCA.

Summary: The Type 1 diabetes (T1D) is an autoimmune disease mediated by T lymphocyte multifactorial result of the selective destruction of pancreatic islets in the insulin-producing cells. The risk to suffer T1D is determined by a complex interaction between multiple genes and environmental factors. Although the disease is strongly associated with major histocompatibility complex (MHC), there are more than 18 potential loci identified thus far. We analyzed the genetic markers MHC in a case control study with 302 patients T1D and 529 controls. The frequency phenotypic DR3-TNFa1b5 was higher in patients heterozygous T1D DR3-positivos that controls DR3 heterozygotes DR3-positivos. These data were confirmed by analyzing allelic frequencies and using the program to review Arlequin haplotypes DR3-positivos. These data were confirmed by analyzing allelic frequencies and using the program to review Arlequin haplotypes DR3-positivos. Our results support unequivocally the existence of a second in the region susceptibility haplotype ancestral 18.2 in the Spanish population. In addition, our results suggest that exist in the MHC haplotype of susceptibility and / or additional protection to DR3-DQ2, DR4-DQ8 and DR2-DQ6. It's clear that the MHC is responsible for about half of the susceptibility to T1D. However, it has been noted that changes in the balance of responses Th1/Th2 seem to play an important role in the development of autoimmune diabetes in fact the disease is correlated with the production of cytokines type 1, while the protection for the disease is associated with cytokines type 2. For an overview decided to make a range of cytokines from both groups. So within the first group we studied interleukin-12 (IL-12) and interferon (IFN) and the second group IL-10 and IL-4. The gene IL-10 we have analyzed 3 polymorphisms of a single nucleotide (SNPs) in the promoter region and 2 microsatellite (IL-10G and IL-10R) in the vicinity of the gene. We found a positive association of alleles IL-10G * 12 and IL-10G * 14 with the disease, association previously observed with other diseases Th1 such as multiple sclerosis and rheumatoid arthritis in the case of IL-10G * 12 and the Crohn's disease for the allele IL-10G * 14. In the case of another cytokine Th2 studied (IL-4) none of the markers analyzed were found associated with T1D. With regard to the polymorphisms in the regions where they are located genes cytokines Th1 (IL12B and IFNG), we believe the frequencies haplotipicas through the program Arlequin. Of all the haplotypes are analyzed two significantly associated with the disease, one in the region IL12B and another including gene IFNG. In addition, we found a haplotype IL12B protector.

Author: FERNÁNDEZ NÚÑEZ JUAN M..
Year: 2004.
University: EXTREMADURA [www.unex.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD MEDICINA (BADAJOZ).

Summary: The familial hypercholesterolaemia (HF) to join disorders mogénicos more common in the human pathology. It occurs in 1 / 500 people heterocigotas and 1 / 1000000 for --. Patients have a high coronary risk in young ages of gracious living. The biochemical alteration is a mutation in the gene receptor CD. We have studied 100 patients with a clinical diagnosis of HF in Extremadura. We present data from the clinical study, the prevalence of cardiovascular disease in patients early and first-degree relatives, as well as factors predictos of cardiovascular risk in this population. It also explores imitations of the gene R-LDL found. Comparisons are made with the major studios nationally and internationally.

Author: CORDOBÉS LÓPEZ JESÚS.
Year: 2004.
University: SEVILLA [www.us.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: UNIDAD DE INVESTIGACIÓN. ÁREA SANITARIA DE OSUNA - SEVILLA.

Summary: INTRODUCTION type 2 diabetes represents an important cause of morbidity and mortality and permanent disability in developed countries. The association with other cardiovascular risk factors, especially hypertension, dyslipidemia and consumption of snuff, it increases the probability that the diabetic submit a vascular event. At present there is a consensus to carry out an intensive treatment of these cardiovascular risk factors in the diabetic population. Lipid-lowering therapy with HMG-CoA reductase inhibitors (statins) has shown a reduction in mortality from cardiovascular events, but there are few studies that assess the decrease in the incidence of cardiovascular disease in patients with type 2 diabetes. The atherosclerosis is a multifactorial process, involving both genetic and environmental factors: it is increasingly aware of the relationship between certain genetic polymorphisms, altering the condition that lipoprotein metabolism and modulation of vascular risk they cause. One of the most polymorphisms associated with the alteration of lipoprotein metabolism and cardiovascular disease is the apolipoprotein C-III gene. It is not known the potential influence of genetic polymorphism of the apo C-III on the modulation of lipoprotein metabolism of semivastatina in type 2 diabetics with dyslipidemia. Objectives To assess the degree of control of different cardiovascular risk factors in type 2 diabetics with dyslipidemia, after 6 months of follow-up, and determine the therapeutic response of simvastatin during that period. To determine the frequency and impact of polymorphism of apolipoprotein C-III on metabolic control, its relationship with cardiovascular risk factors and the presence or absence of macroangiopatía diabetic. DESIGN Study quasiexperimental of therapeutic intervention with simvastatin, longitudinal and prospective, conducted on a population of type 2 diabetics with high cholesterol, followed for 6 months, chosen at random from the consultations of Family Medicine and Internal Medicine Area Health Osuna, divided in two groups, in a non-random, without macroangiopatía diabetic (sMD) and diabetic macroangiopatía (sMD). MATERIALS AND METHODS Patients type 2 diabetics with high cholesterol aged 40-80 years, were followed up for 6 months, divided into 3 consultations (baseline, 3 months and final), which identified the anthropometric data and the different metabolisms involved. It identified the genetic polymorphisms in the apolipoprotein C-III, the apolipoprotein E of glycogen synthase and receptor beta-3-andrenérigco. RESULTS With a sample size of 101 patients (45 men and 56 women) with an average age of 66 years, the distribution groups was similar (sMD: 35.6% and cMD: 46.5%). The simvastatin in doses of 20 mg per day resulted in a reduction of 23.5% in total cholesterol and 31% of c-LD: already dose of 40 mg per day of the statin the fall was 31% of total cholesterol and 41% of c-LDL. The decline in coronary risk in type 2 diabetic patients with hypercholesterolemia and non-smokers was 32% in males and 36% in females. The distribution of genetic polymorphism of our series was 85% with genotype S1S1 and 15% of genotype S1S2, was not found regarding the presence of cardiovascular disease. Patients with allele rare S2 and the most common haplotype (TT, A1A1 and E3E3) had a higher reduction with 20 mg of simvastatin daily in total cholesterol (-22% vs. -32%), c-LDL (- 30% vs -44%) than those with genotype S1S1. Conclusions The therapeutic intervention in type 2 diabetics with hipercolestolemia during 8 6 months 54e got a decrease in vascular risk by increasing physical activity and decreasing levels plasmásticos of c-LDL and microalbumunuria. Obesity had a high prevalence and determining the perimeter of the waist was the variable most often associated with vascular disease. The polymorphism of the apo C-III not moduló risk factors caridovascular of our type 2 diabetic patients with hypercholesterolemia, and was not related to the presence or absence of macroangiopatía diabetic. Patients with genotype S1S2, and the most common haplotype are hiperespondedores to treatment with 20 mg and simvastatin respect to genotype S1S1.

Author: Relaño Reyes Eva.
Year: 2004.
University: ZARAGOZA [www.unizar.es].
Place of defense: Facultad de Medicina.
Place of preparation: Facultad de Ciencias.

Summary: Breast cancer is the most common tumor in women, accounting for 32% of neoplastic diseases, and the biggest cause of death among women in industrialized countries. One of the main problems of neoplastic diseases is the lack of response to treatment or developed resistance to it by some patients, as well as the different developments sick with the same initial clinical feature, which would suggest at the outset a similar behavior . P53 is involved in cell cycle arrest, apoptosis and DNA repair, being frequently mutated in cancers. However, the exact role played p53 in the development of breast cancer and response to therapy is to be defined. Therefore, our goals were: 1. To determine the prevalence of mutations in p53 in tumor tissue of locally advanced breast cancer. 2. Identifying the possible relationship between the presence of mutations in p53 and other variables of prognostic value in breast cancer. 3. To evaluate the possible role of the presence of mutations in p53 in tumor tissue as a factor predictive of response in patients with locally advanced breast cancer treated with neoadjuvant therapy with anthracyclines. 4. To evaluate the possible role of the presence of mutations in p53 in tumor tissue as a prognostic factor in patients with locally advanced breast cancer treated with neoadjuvant therapy with anthracyclines. It proceeded to the sequencing of exons from 5 to 9 p53 through médodo of dideoxinucleótidos triphosphate scored in 100 patients with locally advanced breast cancer treated with neoadjuvant chemotherapy with anthracyclines. It was also analyzed by the model mutacional by computer system Swiss-Pdb Viewer 3.4., The possible effect of the mutations found in the protein TP53. It identified 16 mutations in a different direction, 7 in the same direction, 2 deletions, 1 insertion, 1 mutation ayuste and 1 mutation in 25 patients senseless, as three sick Two mutations. In these three patients were detected a mutation in the same direction, and two of them also a mutation in a different direction, while the third insertion. For reasons of sample size, split the sick in Class A (sick without mutations or possibly a recessive mutations: changes in the same vein, the insertion, deletions, and the mutation nonsense mutation ayuste ) and Class B (patients with mutations in a different sense) The presence of mutations in p53 in a different sense in tumor tissue was independent of the stadium menopáusico of the sick at the time of diagnosis, histologic grade of the tumor, the expression of the gene Her2 / neu and the expression of estrogen receptors and progesterone. Although the presence of mutations in a different direction was independent of the clinical stage of the tumor, to break down the stage clinical tumor stage and lymph node is found that is related to the stage of primary tumor, but not with lymph node Stadium. Lastly, the presence of mutations was also related to the tumor size and histological type. As for the value of the presence of mutations in a different sense in p53 as a factor predictive of response, while patients with complete response to treatment had no such mutation, the difference was not statistically significant. Finally, the presence of mutations in a different sense in p53 is related to the overall survival of the patient as well as the death from breast cancer. Not true in the case of relapse and disease-free survival, and that while sick with mutations in a different direction suffer a relapse more often and have a free survival and 8 nfermeda 2cd d minor, the difference between the two groups is not statistically significant.

Author: CHICA DÍAZ ROSA ANA DE LA.
Year: 2005.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: AUTONOMA DE BARCELONA.
Place of preparation: UNIDAD BIOLOGÍA CELULAR Y GENÉTICA MÉDICA.

Summary: The SNUFF increases the risk of different diseases: clotting problems, chronic pulmonary obstructive disease, cancer and adverse effects on pregnancy. Recently, several authors have detected the presence of specific snuff metabolites in the urine of infants and liquid amniótico of pregnant smokers, suggesting a possible genotoxic effect at early stages of embryonic development. Currently data to detect the possible effect of transplacental snuff during pregnancy are controversial. There are only two studies using indirect coriales villi. The objectives of this study were: 1) Design of the art uniforme-bandas Ga from extensions amniocitos obtained previously for diagnostic. 2) Analysis of chromosomal instability and chromosomal abnormalities in cells of amniotic fluid 3) Analysis of the points of rupture involved in the injury and chromosomal abnormalities In this prospective study has analyzed a total of 50 samples of amniotic fluid different from women divided into two groups 25 pregnant smokers of 10-20 cigarettes a day for at least 10 years and continued to smoke during pregnancy and 25 pregnant non-smokers and non-exposed ahumo cigarette or at home or in the workplace (non-smokers passive). It required 800 surveys. The chromosomal instability was analyzed with staining uniforme-bandas G. Comparison of cytogenetic data between pregnant smokers and non-smokers showed significant differences between the proportion of structural chromosomal abnormalities (P = 0.002) and to a lesser extent in the proportion of metaphases with chromosomal instability, (P = 0.04), and the proportion of chromosome damage (P = 0.045) The statistical analysis of the 689 points of rupture showed that the band 11q23, which is more involved in diseases oncohematológicas, was the chromosomal region most affected by the snuff. Our results show the following conclusions: 1 .- The habit of smoking among women in quantities of 10 or more cigarettes daily for a long period (10 years or more) and especially during pregnancy influences the increase in chromosomal instability observed in amniocitos. 2 .- The age of mothers, but significantly higher in the group of smokers than in the control (3 years apart), no effect on the increase of chromosomal instability observed in amniocitos. 3 .- In comparing the results obtained in cytogenetic fetuses exposed in utero to snuff (F) and controls (C) there are significant differences in the proportion of structural chromosomal abnormalities [P = 0,002; F: 12.1% (96/793 ), C: 3.5% (26/752)] and to a lesser extent in the proportion of metaphases with chromosomal instability [P = 0.04; F: 10.5% (262/2492) and C: 8.0% (210 / 2637)] and the proportion of chromosomal lesions [P = 0,045; F: 15.7% (8391/2492) and C: 10.1% (267/2637)] 4 - The distribution of 689 points breakage involved in injuries and structural alterations in both groups was not random and there is a preferential location where gangs have been described fragile sites (P less than 0.01). 5 .- The band 3p14.2, where the place fragile FRA3B most frequently expressed, has only been found in the affected group of smokers, indicating that the expression of FRA3B is directly related to snuff. 6 .- We have identified three chromosomal bands particularly affected by exposure to snuff: 5q31, 17q21 and above the 11q23 7 .- The band 11q23, which we have identified as particularly sensitive to the components of snuff, is heavily involved in the pediatric haematological malignancies. The other two bands, 5q31 and 17q21, are also involved with child processes leucémicos aunq 8 ue in mu 3ea cho lesser extent 8 .- Our results support the hypothesis that in the fetus, exposure to the components of snuff crossing the placenta might be associated with processes oncohematológicos pediatric, although epidemiological studies will be needed to establish the association between smoking and increased risk of blood cancer in children.

Author: PRAT PEDROLA ESTER.
Year: 2005.
University: AUTÓNOMA DE BARCELONA [www.uab.es].
Place of defense: FACULTAT DE MEDICINA..
Place of preparation: UNITAT DE BIOLOGIA, FACULTAT DE MEDICINA.

Summary: Cancer is a group of more than 100 diseases that are characterized by the accumulation of multiple genetic alterations. Of the various diseases that are included in this terminology, we have focused on the study of three types of solid tumors epithelial: sporadic bladder tumors, tumors or relatives of hereditary colorectal cancer and kidney cancer. To make the studies comprising this thesis, the technique has been used in more routine has been Comparative Genomic Hybridization (CGH). The comprehensive analysis of the genome that allows this technique provides information on desquilibrios, either gains or losses, which occur on a more frequent and therefore it would be regions that may contain tumor suppressor gene or oncogene well also permits to carry out studies and clonalidad detect diferrentes patterns converging or diverging chromosomal evolution. Regarding bladder tumors, these are very heterogeneous both morphologically as clinically, it is for this reason that one of the goals that we considered was the fact provide new data on genomic imbalances of these tumors. In our studies we find that the transitional cell tumors (CBT) of the bladder, genomic damage increased with tumor stage and grade, being imbalances Frequently, corresponding to the losses of 9q, 9p, 5q, 8p and earnings of 1q, Xq, 17q, 8q i 20q. However, a number of changes which have significant differences between the various stages tumor. The changes presented significant differences between the stadiums pTa and pT1 are loss of 5q, 9p, 9q, 10q, 8p, 11q, 18q and gains 8q, 10p. While between tumors pT1 i pT2-T4, and those differences are significant gains 5p, 7p, 3p, 10p and the loss of 6q. As a high number of tumors (CBT) were studied superficial tumors or minimally infiltrantes also classificamos these tumors based on the patterns of genomic imbalances observed, so that revealed the existéncia three subgroups: one characterized by the predominance profit, the most frequent of: 1q, 1p, 17q and 19p, the second marked by losses principally affecting chromosome following regions: 9q, 9p, 11q, 8p, 5q, 11p, and a third group characterized by the presence of a small number of imbalances. Finding two subgroups with complex karyotypes may suggest that the evolution of these tumors occur at least two tracks, one marked by gains and losses other. On the other hand, 30% of tumors uroteliales presented multifocalidad or multiple injuries, a fact that makes these tumors in a unique model for the analysis of the relationship between sporadic synchronous tumors. The study of these tumors synchronous of a patient confirmed their origin monoclonal us and enabled us to chart ways of changing from a single original tumor. As far as studies of synchronous tumors family is concerned, we did two studies, one of them with tumors of patients suffering from kidney Papilar Hereditary Cancer (HPRC), and another with tumors of patients with Familial Adenomatous Polyposis (FAP), the study these tumors provides an excellent model for studying natural alterations present in the early stages of tumor development at the same time and provide important information on the dynamic alterations in the formation of these tumors. As the study of HPRC concerns were obs 8 ervaron 790 the presence of chromosomal structural alterations identical in different tumors from the same patient fact that suggests a common origin embryonic, or genetic predisposition may make the acquisition of chromosomal abnormalities in regions specific. In addition, these patients were studied at the behavior of MET (patients who suffer from this disease are characterized by a mutation of this proto in the germ line, which predisposes to the families who have this mutation to HPRC); this study note that the doubling of the guy carrying the gene mutation germ, it is associated with the trisomía 7. In those tumors with tetrasomia 7 was observed doubling as both the mutated allele of the normal allele. As far as the study of patterns of evolution in colorectal cancer is concerned, this was done from the imbalances present in adenomas and carcinomas from patients with tumors of FAP; note that the various adenomas from the same patient showed a clear link genetics, indicating a common pattern of evolution. This suggests again that genetic predisposition may make the acquisition of genomic alterations in specific chromosomal subregions.

Author: GORDILLO URBANO RAFAEL MANUEL.
Year: 2005.
University: CÓRDOBA [www.uco.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The hepatitis C virus (HCV) is a virus worldwide distribution which has a prevalence of infection varies among different countries but it is estimated that between 150 and 200 million people. It is a virus RNA positive polarity with approximately 9.5 Kb and a size of between 55 and 65 nm. One of the salient features of the Hepatitis C virus is its ability to change that occurs primarily embodiments erroneous nucleotide by homologous recombination between viruses with similar sequences or non - homologous recombination between viruses in different sequences. This gives rise to different genotypes, subtypes and cuasiespecies according to their degree of homology. In addition to its importance as a marker epidemic, the virus genotyping in the case of HCV, has interest from the point of view prognosis and therapeutic. With this paper we propose to determine the distribution of genoptipos Hepatitis C in patients infected with the virus C in the province of Cordoba, establishing the relationship between HCV genotype and the mode of acquisition of infection; see what relationship among the genotype of the virus C alteration between different biochemical and histological parameters, to determine the significance of viral genotype on response to treatment in patients who receive it. This has made the determination of viral genotype to 511 patients with chronic HCV infection from different services and has been studied in a retrospective clinical records of 138 patients from the unit hepatology. The genotype most common among all the sick that he had been given is 1b. We found the relationship between acquiring the disease and genotype infective. We found a significantly higher viral load in patients infected with genotype 1. Patients treated with inteferón pegylated in combination with ribavirin have a higher response rate than those receiving standard interferon and ribavirin.

Author: FERNÁNDEZ MATA IGNACIO.
Year: 2005.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE MEDICINA DE LA UNIVERSIDAD DE OVIEDO.
Place of preparation: UNIVERSIDAD DE OVIEDO.

Summary: In recent years, the biggest advance in the understanding of the etiology of Parkinson's disease (PD) has been the identification of several genes involved in the familiar. In this study we conducted an analysis of the spectrum mutacional four of these genes, SNCA, PRKN, PINK1 and LRRK2, in 411 patients of Asturias. These genes were chosen because of their importance in the development of the JV, both by a high rate of mutations in patients for the functional significance of the protein encoded. To study the molecular employ techniques such as DNA amplification (PCR), indirect detection of changes sequential (SSCA), direct sequencing, analysis of gene dosage, genotipado by PCR-RFLP or Tagman, among others. The results we obtained show that mutations in the genes PRKN and LRRK2 could be found in about 10% of patients, a frequency so far not found in other populations. While additional studies are needed to assess the significance of these gene variants in the origin and progression of the neurodegenerative process, knowledge of the molecular basis of the disease could have an application in the clinic, both to facilitate the diagnosis and genetic council, as for studies of response to therapy (pharmacogenetics / pharmacogenomics).