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Vacas en una pradera. © Inra, DELABY Luc

Las vacas, «supermodelos» de la investigación

La vaca puede ser un modelo pertinente para el estudio de las anomalías genéticas humanas. Esta es la conclusión a la que llegó un equipo internacional encabezado por el INRA –en colaboración con ALLICE, CEA y VetAgroSup en lo que respecta a Francia–,* publicada en la revista Scientific Reports. El estudio de mutaciones responsables de síndromes raros en el bovino que también se han observado en el ser humano ofrece una alternativa interesante a los animales de laboratorio cuando se trata de confirmar el origen genético de dichas enfermedades y determinar los mecanismos moleculares subyacentes.

Actualización: 20/10/2017
Publicación: 18/09/2017
Palabras clave: Genética - vaca

El reducido número de pacientes afectados y los problemas que conlleva el desarrollo de cepas de modelos animales para las anomalías genéticas dominantes más graves con frecuencia obstaculiza la descripción clínica y el estudio molecular de los síndromes raros en el ser humano. Por el contrario, la estructura de las poblaciones bovinas y la cantidad de datos fenotípicos y genómicos disponibles de esta especie permiten identificar rápidamente las mutaciones causales y estudiar sus efectos en grandes cohortes de animales afectados.

Un equipo internacional encabezado por el INRA, en colaboración con ALLICE, CEA y VetAgroSup,* buscó mostrar, mediante una selección de ejemplos, las numerosas oportunidades que ofrece el modelo bovino. Los investigadores identificaron mutaciones candidatas para siete anomalías genéticas dominantes1 mediante la secuenciación del genoma completo de un animal afectado y su contrastación con los genomas de más de mil individuos de control que representaban los principales antepasados de sus respectivas razas. Posteriormente, al estudiar los individuos emparentados con los animales afectados, pudieron confirmar que dichas mutaciones habían surgido de novo y que eran la causa de dichos síndromes.

Además, los científicos realizaron exámenes clínicos y observaron correlaciones genotipo-fenotipo perfectas entre los casos bovinos y los pacientes humanos que presentaban mutaciones en los mismos dominios de las mismas proteínas, demostrando de este modo que la vaca podía ser un modelo pertinente para el estudio de anomalías genéticas humanas. De este modo evidenciaron que el modelo bovino puede, en ciertos casos, resultar más adecuado que el modelo murino, que expresa a veces un fenotipo atenuado.

Demostraron igualmente que las grandes familias de medios hermanos obtenidas mediante inseminación animal permiten cartografiar los genes modificadores2 y que el estudio de mutaciones raras en el bovino también puede revestir un interés para la investigación básica.

Por último, los científicos mostraron que se puede anticipar la aparición de algunas anomalías genéticas recesivas al identificar ciertos toros de inseminación portadores de eventuales mutaciones de novo perjudiciales. De este modo, es posible evitar que dichas anomalías se manifiesten en las poblaciones.

En conclusión, el estudio permite considerar en detalle el potencial que tiene la utilización de las especies ganaderas como modelos animales en la era posgenómica.

1 El artículo presenta casos de acondrogénesis de tipo II (provocadas por tres mutaciones distintas en el gen COL2A1), síndrome de CHARGE (CHD7), osteogénesis imperfecta de tipo II (COL1A1), síndrome de Tietz (MITF), displasia ectodérmica anhidrótica, así como una anomalía de coloración, que no se ha observado en el hombre, llamada rojo dominante (COPA).

2 Al interactuar con el gen mutado, los genes modificadores pueden agravar o, al contrario, atenuar los síntomas asociados con ciertos síndromes de origen genético.

* Con la participación del Instituto de la Ganadería (Idele), el Observatorio Nacional de las Anomalías Bovinas (ONAB), LABOGENA y la Escuela Nacional Veterinaria, Agroalimentaria y de la Alimentación Nantes-Atlántico (ONIRIS).

Contacto
Contacto científico:

  • Aurélien Capitan (33 (0)1 34 65 26 45) Unidad Mixta de Investigación «Genética Animal y Biología Integrativa» (INRA, AgroParisTech)
Contacto de prensa:
Servicio de prensa del INRA (33 (0)1 42 75 91 86)
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Animal Genetics
Centro asociado:
Jouy-en-Josas

Referencia

E. Bourneuf, P. Otz et coll. Rapid Discovery of De Novo Deleterious Mutations in Cattle Enhances the Value of Livestock as Model Species. Scientific Reports. 13 de septiembre de 2017. DOI : 10.1038/s41598-017-11523-3