{"id":95982,"date":"2018-03-11T10:16:08","date_gmt":"2018-03-11T10:16:08","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/splicing-anomalo-de-los-genes-brca1-y-brca2-y-susceptibilidad-genetica-a-cancer-de-mama-y-ovario\/"},"modified":"2018-03-11T10:16:08","modified_gmt":"2018-03-11T10:16:08","slug":"splicing-anomalo-de-los-genes-brca1-y-brca2-y-susceptibilidad-genetica-a-cancer-de-mama-y-ovario","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/genetica\/splicing-anomalo-de-los-genes-brca1-y-brca2-y-susceptibilidad-genetica-a-cancer-de-mama-y-ovario\/","title":{"rendered":"Splicing an\u00f3malo de los genes brca1 y brca2 y susceptibilidad gen\u00e9tica a c\u00e1ncer de mama y ovario"},"content":{"rendered":"<h2>Tesis doctoral de <strong> David Jos\u00e9 Sanz San Jos\u00e9 <\/strong><\/h2>\n<p>El espectro de predisposici\u00f3n gen\u00e9tica a c\u00e1ncer de mama y ovario ha sido resuelto tan solo parcialmente. Un gran n\u00famero de mutaciones han sido descritas, principalmente sustituciones de nucle\u00f3tido y peque\u00f1as inserciones o deleciones en la regi\u00f3n ex\u00f3nica de los genes de alta susceptibilidad a c\u00e1ncer de mama y ovario hereditario brca1 y brca2. Sin embargo el efecto en la enfermedad de la mayor\u00eda de mutaciones no truncantes en estos genes a\u00fan es desconocido. el efecto delet\u00e9reo de una mutaci\u00f3n predicho en base a la traducci\u00f3n directa del cambio que supone la mutaci\u00f3n en la secuencia g\u00e9nica puede ser radicalmente alterado si la mutaci\u00f3n induce un cambio en el procesamiento por splicing del transcrito primario. este trabajo desarrolla un m\u00e9todo de an\u00e1lisis funcional del efecto de mutaciones en el splicing  basado en la construcci\u00f3n y mutag\u00e9nesis dirigida de minigenes h\u00edbridos y su ensayo en c\u00e9lulas hela y mcf10a, lo que reduce dr\u00e1sticamente la necesidad de contar con muestras biol\u00f3gicas de arn de los enfermos portadores de mutaciones para ensayar mediante rt-pcr su posible efecto en el splicing del transcrito primario. hemos ensayado el efecto de 103 variantes en el splicing, de las que hasta 36 provocaban alteraciones en el splicing. Hasta el 60% de las familias analizadas en nuestro laboratorio con un test brca1+ son portadoras de una mutaci\u00f3n que afecta al splicing, lo que es indicador de la importancia de las alteraciones de este mecanismo de procesamiento en la enfermedad. hemos comprobado que  mutaciones de  muy distinto tipo provocan alteraciones en el splicing tanto en linfocitos de pacientes portadores como en c\u00e9lulas transfectadas con los minigenes mutantes construidos.  tras discutir los posibles efectos que la presencia de distintos transcritos incorrectamente procesados, puede tener sobre la predicci\u00f3n de patogeneicidad de las distintas mutaciones proponemos que la toma en consideraci\u00f3n de los defectos en el splicing puede aumentar el porcentaje de casos de c\u00e1ncer de mama y ovario hereditario explicados por mutaciones en los genes brca1 y brca2 y que el modelo te\u00f3rico de c\u00e1ncer de mama y ovario hereditario debe ser en consecuencia revisado.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Splicing an\u00f3malo de los genes brca1 y brca2 y susceptibilidad gen\u00e9tica a c\u00e1ncer de mama y ovario<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Splicing an\u00f3malo de los genes brca1 y brca2 y susceptibilidad gen\u00e9tica a c\u00e1ncer de mama y ovario <\/li>\n<li><strong>Autor:<\/strong>\u00a0 David Jos\u00e9 Sanz San Jos\u00e9 <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Valladolid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 18\/09\/2009<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Eladio Andr\u00e9s Velasco Sampedro<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: joaqu\u00edn Rueda puente <\/li>\n<li>Jos\u00e9 ignacio Mayordomo camara (vocal)<\/li>\n<li>eduardo Arranz sanz (vocal)<\/li>\n<li>Jes\u00fas Garcia foncillas lopez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de David Jos\u00e9 Sanz San Jos\u00e9 El espectro de predisposici\u00f3n gen\u00e9tica a c\u00e1ncer de mama y ovario ha [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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