Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19
Entre las causas femeninas de infertilidad, la Falla Ovárica Prematura (FOP) es frecuente, ya que afecta al 1% de las mujeres menores de 40 años de edad (Coulam et al, 1986). La FOP se define clínicamente por amenorrea de más de 6 meses de duración, niveles plasmáticos elevados de gonadotrofinas y d...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2016
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- Universidad del Rosario
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- Repositorio EdocUR - U. Rosario
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- spa
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/13388
- Acceso en línea:
- https://doi.org/10.48713/10336_13388
http://repository.urosario.edu.co/handle/10336/13388
- Palabra clave:
- Falla Ovárica Prematura
Secuenciación de siguiente generación
Análisis funcionales
Evolución & genética
Genética conductual
Etiología
Infertilidad Femenina
Salud Pública
Failure Ovarian premature
Next generation sequencing
functional in vitro test
variants
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- Abierto (Texto completo)
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| dc.title.spa.fl_str_mv |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 |
| title |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 |
| spellingShingle |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 Falla Ovárica Prematura Secuenciación de siguiente generación Análisis funcionales Evolución & genética Genética conductual Etiología Infertilidad Femenina Salud Pública Failure Ovarian premature Next generation sequencing functional in vitro test variants |
| title_short |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 |
| title_full |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 |
| title_fullStr |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 |
| title_full_unstemmed |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 |
| title_sort |
Disección molecular de la etiología de la falla ovárica prematura por secuenciación directa y NGS: estudio de la implicación de los genes CITED2, CDKN1B, FOXO4, BMP15 y ADAMTS19 |
| dc.contributor.advisor.none.fl_str_mv |
Laissue, Paul |
| dc.subject.spa.fl_str_mv |
Falla Ovárica Prematura Secuenciación de siguiente generación Análisis funcionales |
| topic |
Falla Ovárica Prematura Secuenciación de siguiente generación Análisis funcionales Evolución & genética Genética conductual Etiología Infertilidad Femenina Salud Pública Failure Ovarian premature Next generation sequencing functional in vitro test variants |
| dc.subject.ddc.none.fl_str_mv |
Evolución & genética |
| dc.subject.decs.spa.fl_str_mv |
Genética conductual Etiología Infertilidad Femenina Salud Pública |
| dc.subject.keyword.eng.fl_str_mv |
Failure Ovarian premature Next generation sequencing functional in vitro test variants |
| description |
Entre las causas femeninas de infertilidad, la Falla Ovárica Prematura (FOP) es frecuente, ya que afecta al 1% de las mujeres menores de 40 años de edad (Coulam et al, 1986). La FOP se define clínicamente por amenorrea de más de 6 meses de duración, niveles plasmáticos elevados de gonadotrofinas y deficiencia de esteroides sexuales antes de los 40 años de edad. La FOP puede ocurrir por una variedad de mecanismos que conducen a la disminución del número de folículos, al incremento de la atresia folicular o a la falla en la maduración de los folículos (Beck-Peccoz et al, 2006). La FOP se ha asociado a varias etiologías, pero en más del 80% de los casos, no se conoce la causa de la enfermedad. Esta alta prevalencia de casos idiopáticos sugiere la implicación de factores genéticos y ambientales (Maclaran et al, 2011). La complejidad de los procesos fisiológicos, celulares y genéticos subyacentes a la determinación sexual, la foliculogénesis y la ovulación sugiere la participación de numerosos genes regulados de una manera precisa en cada etapa del desarrollo (Laissue, 2015). En este contexto, es fundamental integrar el alcance de las distintas técnicas para la búsqueda de factores genéticos etiológicos de la FOP. En efecto, tanto la secuenciación directa como las aproximaciones multigénicas para el análisis genómico a gran escala son aproximaciones complementarias para este ejercicio. La iniciativa principal de este trabajo doctoral consistió en realizar aproximaciones monogénicas (secuenciación de Sanger) y multigénicas Next generation sequencing (NGS) para la identificación de nuevos genes asociados a FOP. La identificación de nuevos genes y de variantes potencialmente deletéreas, así como su validación a través de estudios funcionales y análisis poblacionales, permitió aportar nuevo conocimiento en la etiología molecular de la FOP |
| publishDate |
2016 |
| dc.date.created.none.fl_str_mv |
2016-05-13 |
| dc.date.issued.none.fl_str_mv |
2016 |
| dc.date.accessioned.none.fl_str_mv |
2017-05-17T16:49:34Z |
| dc.date.available.none.fl_str_mv |
2017-05-17T16:49:34Z |
| dc.type.eng.fl_str_mv |
doctoralThesis |
| dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_db06 |
| dc.type.spa.spa.fl_str_mv |
Tesis de doctorado |
| dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.48713/10336_13388 |
| dc.identifier.uri.none.fl_str_mv |
http://repository.urosario.edu.co/handle/10336/13388 |
| url |
https://doi.org/10.48713/10336_13388 http://repository.urosario.edu.co/handle/10336/13388 |
| dc.language.iso.none.fl_str_mv |
spa |
| language |
spa |
| dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto completo) |
| rights_invalid_str_mv |
Abierto (Texto completo) http://purl.org/coar/access_right/c_abf2 |
| dc.format.mimetype.none.fl_str_mv |
application/pdf |
| dc.publisher.spa.fl_str_mv |
Universidad del Rosario |
| dc.publisher.department.spa.fl_str_mv |
Facultad de Ciencias Naturales y Matemáticas |
| dc.publisher.program.spa.fl_str_mv |
Doctorado en Ciencias Biomédicas |
| institution |
Universidad del Rosario |
| dc.source.bibliographicCitation.none.fl_str_mv |
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Laissue, Paul79782770600Fonseca Mendoza, Dora JanethDoctor en Ciencias Biomédicas520948256002017-05-17T16:49:34Z2017-05-17T16:49:34Z2016-05-132016Entre las causas femeninas de infertilidad, la Falla Ovárica Prematura (FOP) es frecuente, ya que afecta al 1% de las mujeres menores de 40 años de edad (Coulam et al, 1986). La FOP se define clínicamente por amenorrea de más de 6 meses de duración, niveles plasmáticos elevados de gonadotrofinas y deficiencia de esteroides sexuales antes de los 40 años de edad. La FOP puede ocurrir por una variedad de mecanismos que conducen a la disminución del número de folículos, al incremento de la atresia folicular o a la falla en la maduración de los folículos (Beck-Peccoz et al, 2006). La FOP se ha asociado a varias etiologías, pero en más del 80% de los casos, no se conoce la causa de la enfermedad. Esta alta prevalencia de casos idiopáticos sugiere la implicación de factores genéticos y ambientales (Maclaran et al, 2011). La complejidad de los procesos fisiológicos, celulares y genéticos subyacentes a la determinación sexual, la foliculogénesis y la ovulación sugiere la participación de numerosos genes regulados de una manera precisa en cada etapa del desarrollo (Laissue, 2015). En este contexto, es fundamental integrar el alcance de las distintas técnicas para la búsqueda de factores genéticos etiológicos de la FOP. En efecto, tanto la secuenciación directa como las aproximaciones multigénicas para el análisis genómico a gran escala son aproximaciones complementarias para este ejercicio. La iniciativa principal de este trabajo doctoral consistió en realizar aproximaciones monogénicas (secuenciación de Sanger) y multigénicas Next generation sequencing (NGS) para la identificación de nuevos genes asociados a FOP. La identificación de nuevos genes y de variantes potencialmente deletéreas, así como su validación a través de estudios funcionales y análisis poblacionales, permitió aportar nuevo conocimiento en la etiología molecular de la FOPPremature ovarian failure (POF) is a frequent disease, affecting 1% of women under 40 years old (Coulam et al, 1986). Clinically, POF women are affected by primary or secondary amenorrhoea and increased plasma levels of gonadotrophins (e.g. FSH and LH). POF can be originated from a variety of mechanisms leading to a decrease in the number of follicles, to the increase of follicular atresia or to follicle maturation failure (Beck-Peccoz et al, 2006). POF has been associated with different etiologies, but in the majority of the cases the cause remains unknown. The prevalence of idiopathic cases suggests the existence of genetic and environmental aetiological factors (Maclaran et al, 2011). The inherent molecular complexity of sex determination, folliculogenesis and ovulation underlines that hundreds of genes might be related to POF phenotype (Laissue, 2015). In this context, direct sequencing of single genes and large scale genomic approaches are complementary tools for identifying new POF molecular actors. The present PhD thesis focused on the use of direct sequencing, NGS and functional in vitro tests allowing the identification and validation of new POF causative sequence variants.application/pdfhttps://doi.org/10.48713/10336_13388 http://repository.urosario.edu.co/handle/10336/13388spaUniversidad del RosarioFacultad de Ciencias Naturales y MatemáticasDoctorado en Ciencias BiomédicasAbierto (Texto completo)EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. 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