Assuntos
Animais Recém-Nascidos/anormalidades , Infecções por Bunyaviridae/veterinária , Doenças dos Bovinos/virologia , Doenças Cerebelares/veterinária , Cerebelo/anormalidades , Orthobunyavirus , Animais , Animais Recém-Nascidos/virologia , Infecções por Bunyaviridae/diagnóstico , Infecções por Bunyaviridae/virologia , Bovinos/virologia , Doenças dos Bovinos/diagnóstico , Doenças Cerebelares/diagnóstico , Doenças Cerebelares/virologia , Cerebelo/virologia , Eutanásia Animal , Evolução Fatal , FemininoRESUMO
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.
Assuntos
Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/genética , Bovinos/genética , Surtos de Doenças , Mutação da Fase de Leitura/genética , Glicoproteínas de Membrana/genética , Seleção Genética , Animais , Pareamento de Bases/genética , Sequência de Bases , Bélgica/epidemiologia , Códon sem Sentido/genética , Simulação por Computador , Regulação da Expressão Gênica , Heterozigoto , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Tamanho do Órgão , Especificidade de Órgãos , Penetrância , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Mitogênicos/genética , Receptores Mitogênicos/metabolismo , Deleção de SequênciaRESUMO
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.