Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico

ilustraciones, fotografías, graficas

Autores:
Ocampo Mahecha, Sandra Jhoana
Tipo de recurso:
Fecha de publicación:
2023
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/83895
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/83895
https://repositorio.unal.edu.co/
Palabra clave:
570 - Biología::576 - Genética y evolución
Fisura del Paladar
Mutación INDEL
Patrón de Herencia
Cleft Palate
INDEL Mutation
Inheritance Patterns
Labio hendido
Paladar hendido
No sindrómico
Secuenciación del genoma completo
IRF6
Simulación computacional
Simulación acoplamiento molecular
Red de genes
Cleft lip
Cleft palate
Non-syndromic
Whole genome sequencing
Molecular docking simulation
Computer simulation
Gene network
Rights
openAccess
License
Atribución-SinDerivadas 4.0 Internacional
id UNACIONAL2_137594253db0a443953fa7cf55659843
oai_identifier_str oai:repositorio.unal.edu.co:unal/83895
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
dc.title.translated.eng.fl_str_mv Functional characterization of variants (SNV, Indels, CNVs) analyzed by computational means in 5 Dominican families with non-syndromic cleft lip and/or palate
title Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
spellingShingle Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
570 - Biología::576 - Genética y evolución
Fisura del Paladar
Mutación INDEL
Patrón de Herencia
Cleft Palate
INDEL Mutation
Inheritance Patterns
Labio hendido
Paladar hendido
No sindrómico
Secuenciación del genoma completo
IRF6
Simulación computacional
Simulación acoplamiento molecular
Red de genes
Cleft lip
Cleft palate
Non-syndromic
Whole genome sequencing
Molecular docking simulation
Computer simulation
Gene network
title_short Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
title_full Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
title_fullStr Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
title_full_unstemmed Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
title_sort Caracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómico
dc.creator.fl_str_mv Ocampo Mahecha, Sandra Jhoana
dc.contributor.advisor.none.fl_str_mv Catalina María, Arévalo Caro
Pinzón Velasco, Andrés Mauricio
dc.contributor.author.none.fl_str_mv Ocampo Mahecha, Sandra Jhoana
dc.contributor.researchgroup.spa.fl_str_mv Grupo de Investigación en Crecimiento y desarrollo Craneofacial
Genética Clínica
dc.contributor.orcid.spa.fl_str_mv Sandra Jhoana Ocampo [0000-0003-2171-6000]
dc.subject.ddc.spa.fl_str_mv 570 - Biología::576 - Genética y evolución
topic 570 - Biología::576 - Genética y evolución
Fisura del Paladar
Mutación INDEL
Patrón de Herencia
Cleft Palate
INDEL Mutation
Inheritance Patterns
Labio hendido
Paladar hendido
No sindrómico
Secuenciación del genoma completo
IRF6
Simulación computacional
Simulación acoplamiento molecular
Red de genes
Cleft lip
Cleft palate
Non-syndromic
Whole genome sequencing
Molecular docking simulation
Computer simulation
Gene network
dc.subject.decs.spa.fl_str_mv Fisura del Paladar
Mutación INDEL
Patrón de Herencia
dc.subject.decs.eng.fl_str_mv Cleft Palate
INDEL Mutation
Inheritance Patterns
dc.subject.proposal.spa.fl_str_mv Labio hendido
Paladar hendido
No sindrómico
Secuenciación del genoma completo
IRF6
Simulación computacional
Simulación acoplamiento molecular
Red de genes
dc.subject.proposal.eng.fl_str_mv Cleft lip
Cleft palate
Non-syndromic
Whole genome sequencing
Molecular docking simulation
Computer simulation
Gene network
description ilustraciones, fotografías, graficas
publishDate 2023
dc.date.accessioned.none.fl_str_mv 2023-05-29T16:52:37Z
dc.date.available.none.fl_str_mv 2023-05-29T16:52:37Z
dc.date.issued.none.fl_str_mv 2023
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/83895
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/83895
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
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dc.format.extent.spa.fl_str_mv 203 páginas
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dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv Bogotá - Medicina - Maestría en Genética Humana
dc.publisher.faculty.spa.fl_str_mv Facultad de Medicina
dc.publisher.place.spa.fl_str_mv Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá
institution Universidad Nacional de Colombia
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spelling Atribución-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Catalina María, Arévalo Caro294e5ba435b3fe763a000a043c1c39e1Pinzón Velasco, Andrés Mauricio366c2eddf6aa24434ee55e57da235448Ocampo Mahecha, Sandra Jhoana6d33dab9057d25da4bebbda2290efc4bGrupo de Investigación en Crecimiento y desarrollo CraneofacialGenética ClínicaSandra Jhoana Ocampo [0000-0003-2171-6000]2023-05-29T16:52:37Z2023-05-29T16:52:37Z2023https://repositorio.unal.edu.co/handle/unal/83895Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, graficasIntroducción: El labio y/o paladar hendido es una anomalía congénita, la más frecuente a nivel facial. Puede tener una etiología multifactorial o genética. En República Dominicana y en particular la región de Cibao, se identifica una alta frecuencia diagnóstica de hendiduras orofaciales; sin embargo, son pocos los estudios alrededor de la anomalía. Objetivo: Determinar la estructura y funcionalidad de variantes (SNV, Indels, CNVs) asociadas con labio y/o paladar hendido no sindrómico en cinco familias dominicanas con herencia autosómica dominante, a través de secuenciación masiva y análisis computacional. Metodología: Se reclutaron cinco familias dominicanas mediante la base de datos de la Fundación Niños que Ríen, a quienes se les realizó árboles genealógicos con datos clínicos y poblacionales sobre tres generaciones en cada familia. Se hizo una revisión clínica sistémica y orofacial, análisis de genoma completo en trío mediante el uso de tecnología Illumina por medio de la plataforma HiSeqX con profundidad promedio de 30X. Se tuvieron en cuenta elementos de la historia clínica y los criterios de clasificación de variantes para la definición final. Se hizo un análisis integral mediante herramientas bioinformáticas a las variantes relacionadas a labio y/o paladar hendido no sindrómico con el fin de entender sus mecanismos biológicos con relación a su funcionamiento y al desarrollo de fisuras orofaciales en los seres humanos, mediante modelamiento de proteínas, construcción de red de genes y acoplamiento molecular. Resultados: Se encontraron ocho variantes relacionadas con riesgo de enfermedades; solo una de ellas fue asociada al desarrollo de fisuras orofaciales: una variante tipo CNV en el gen del factor 6 regulador de interferón (IRF6) con clasificación patogénica identificada en una familia afectada. Los factores ambientales identificados no fueron concluyentes. Se crearon tres modelos de IRF6, uno del dominio a unión a ADN sin cambios patogénicos, otro de la variante con pérdida de los primero tres exones y un último de la proteína completa. Mediante herramientas bioinformáticas se obtuvo un modelo de acoplamiento ADN-Dominio unión ADN de IRF6, no publicado en la literatura previamente. Se construyó una red de genes relacionados a IRF6 y el desarrollo de labio y/o paladar hendido no sindrómico. Conclusiones: Se detectó una variante tipo CNV consistente en una deleción de una copia de los exones 1-3 del gen IRF6 asociada a fisuras orofaciales no reportada previamente en la literatura. Se creó un modelo de acoplamiento de ADN-proteína con IRF6 no publicado en la literatura científica. Se hizo un modelo nuevo de red de genes relacionado a IRF6 y labio y/o paladar hendido no sindrómico. Por otro lado, se resalta la importancia de la realización de pruebas moleculares para ofrecer asesoramiento genético a las familias y pacientes. (Texto tomado de la fuente)Introduction: Cleft lip and/or palate is a congenital anomaly, the most frequent at the facial level. It may have a multifactorial or genetic etiology. In the Dominican Republic and in particular the Cibao region, a high diagnostic frequency of orofacial clefts is identified; however, there are few studies around the anomaly. Objective: To determine the structure and functionality of variants (SNV, Indels, CNVs) associated with non-syndromic cleft lip and/or palate in five Dominican families with autosomal dominant inheritance, through massive sequencing and computational analysis. Methodology: Five Dominican families were recruited through the database of the Niños que Ríen Foundation, to whom family trees were made with clinical and population data on three generations in each family. A systemic and orofacial clinical review was made, complete genome analysis in trio using Illumina technology through the HiSeqX platform with average depth of 30X. Elements of the clinical history and the variant classification criteria were taken into account for the final definition. A comprehensive analysis was made using bioinformatic tools of the variants related to non-syndromic cleft lip and/or palate in order to understand their biological mechanisms in relation to their functioning and the development of orofacial clefts in humans, through protein modeling. Gene network construction and molecular docking. Results: Eight variants related to disease risk were found; only one of them was associated with the development of orofacial clefts: a CNV-type variant in the Interferon Regulatory Factor 6 (IRF6) gene with a pathogenic classification identified in an affected family. The environmental factors identified were not conclusive. Three models of IRF6 were created, one of the DNA-binding domain without pathogenic changes, another of the variant with loss of the first three exons, and a last one of the complete protein. Using bioinformatic tools, a DNA-DNA binding domain coupling model of IRF6 was obtained, not previously published in the literature. A network of genes related to IRF6 and the development of non-syndromic cleft lip and/or palate was constructed. Conclusions: A CNV-type variant consisting of a deletion of one copy of exons 1-3 of the IRF6 gene associated with orofacial clefts not previously reported in the literature was detected. A model of DNA-protein docking with IRF6 not published in the scientific literature was created. A new model of gene network related to IRF6 and non-syndromic cleft lip and/or palate was made. On the other hand, the importance of performing molecular tests to offer genetic counseling to families and patients is highlighted.MaestríaMagister en Genética HumanaLínea de investigación en genética del crecimiento y malformaciones203 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en Genética HumanaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::576 - Genética y evoluciónFisura del PaladarMutación INDELPatrón de HerenciaCleft PalateINDEL MutationInheritance PatternsLabio hendidoPaladar hendidoNo sindrómicoSecuenciación del genoma completoIRF6Simulación computacionalSimulación acoplamiento molecularRed de genesCleft lipCleft palateNon-syndromicWhole genome sequencingMolecular docking simulationComputer simulationGene networkCaracterización funcional de variantes (SNV, Indels, CNVs) analizadas por medios computacionales en 5 familias dominicanas con labio y/o paladar hendido no sindrómicoFunctional characterization of variants (SNV, Indels, CNVs) analyzed by computational means in 5 Dominican families with non-syndromic cleft lip and/or palateTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMOspina Ramirez JJ, Castro David MI, Hoyos Ortiz LK, Montoya Martinez JJ, Porras Hurtado GL. 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Hum Mutat. 2015;36(8):815–822.Fondo Nacional de Innovación y Desarrollo Científico y Tecnológico (FONDOCyT No. 2018-19-2A5-236) de República DominicanaEstudiantesInvestigadoresMaestrosMedios de comunicaciónPadres y familiasPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83895/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL41962214.2023.pdf41962214.2023.pdfTesis de maestría en Genética Humanaapplication/pdf4110250https://repositorio.unal.edu.co/bitstream/unal/83895/2/41962214.2023.pdfa84315dd1b422a32a0c2608aa58bc09aMD52THUMBNAIL41962214.2023.pdf.jpg41962214.2023.pdf.jpgGenerated Thumbnailimage/jpeg5778https://repositorio.unal.edu.co/bitstream/unal/83895/3/41962214.2023.pdf.jpg4a0c83aec3d8eb2fd86aba28c662bae9MD53unal/83895oai:repositorio.unal.edu.co:unal/838952023-08-06 23:03:56.957Repositorio Institucional Universidad Nacional de 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