Revista de Medicina de Laboratorio 00077 / http://dx.doi.org/10.20960/revmedlab.00077

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Priorización de variantes de exoma mediante un sistema automático que emplea términos HPO

José Miguel Lezana Rosales, Diego Tuñón Le Poultel, Juan Francisco Quesada Espinosa, Emma Soengas Gonda, Ana Arteche-López, Carmen Palma Milla, Irene Gómez Manjón, María Isabel Álvarez-Mora, Rubén Pérez de la Fuente, María Teresa Sánchez Calvín, María José Gómez Rodríguez, Marta Moreno García

Prepublicado: 2021-08-06

Publicado: 2021-08-06

VOLUMEN 2, NÚM. 2, mayo-agosto (2021), PAG. 59-69

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Introducción: la secuenciación del exoma completo (WES) representa en la actualidad el estudio de primera elección para diagnosticar molecularmente enfermedades genéticas probablemente monogénicas con elevada heterogeneidad genética, o que solapan fenotípicamente con otras enfermedades y por ello requieren analizar multitud de genes para llegar al diagnóstico. Mediante WES se identifican miles de variantes, cuyo número final depende del tamaño de captura empleado y pipeline bioinformático aplicado. Esto requiere implementar técnicas de filtrado y priorización: una posibilidad es emplear paneles virtuales de genes (WES subpanelado), pero en paneles amplios aparecen multitud de variantes, lo que requiere una evaluación pormenorizada por el analista. El uso de términos de ontología de fenotipo (HPO) permite filtrar las variantes a través de asociaciones HPO-gen y establecer un sistema de priorización. El objetivo de este trabajo es el desarrollo de un sistema de priorización automática de variantes empleando términos HPO. Material y métodos: reanálisis de 33 pacientes diagnosticados previamente por WES subpanelado empleando un sistema de priorización basado en términos HPO y en las características inherentes a las variantes detectadas. Resultados: tras el reanálisis se determinó que las variantes que explicaban el fenotipo clínico se encontraban en las primeras posiciones de la lista de variantes priorizadas (media: 1,43; SD: 0,87). Conclusión: el sistema de priorización desarrollado permite la detección de variantes asociadas a las patologías estudiadas de forma más eficiente que por WES subpanelado, al encontrarse las variantes relacionadas con fenotipo ordenadas según su potencial patogenicidad. Este sistema representaría, por tanto, el primer abordaje en el análisis de variantes genéticas de WES.

Palabras Clave: Genética. Secuenciación masiva. Exoma. Fenotipo. Ontología de gen.

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