Asunto(s)
Animales Recién Nacidos/anomalías , Infecciones por Bunyaviridae/veterinaria , Enfermedades de los Bovinos/virología , Enfermedades Cerebelosas/veterinaria , Cerebelo/anomalías , Orthobunyavirus , Animales , Animales Recién Nacidos/virología , Infecciones por Bunyaviridae/diagnóstico , Infecciones por Bunyaviridae/virología , Bovinos/virología , Enfermedades de los Bovinos/diagnóstico , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/virología , Cerebelo/virología , Eutanasia Animal , Resultado Fatal , FemeninoRESUMEN
We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed.
Asunto(s)
Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/genética , Bovinos/genética , Brotes de Enfermedades , Mutación del Sistema de Lectura/genética , Glicoproteínas de Membrana/genética , Selección Genética , Animales , Emparejamiento Base/genética , Secuencia de Bases , Bélgica/epidemiología , Codón sin Sentido/genética , Simulación por Computador , Regulación de la Expresión Génica , Heterocigoto , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Tamaño de los Órganos , Especificidad de Órganos , Penetrancia , Estabilidad del ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Mitogénicos/genética , Receptores Mitogénicos/metabolismo , Eliminación de SecuenciaRESUMEN
The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.
