RESUMO
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.
Assuntos
Animais Domésticos/genética , Doenças dos Bovinos/genética , Mapeamento Cromossômico , Genes Recessivos/genética , Marcadores Genéticos/genética , Polimorfismo de Nucleotídeo Único/genética , Transportadores de Cassetes de Ligação de ATP/genética , Sequência de Aminoácidos , Animais , Animais Domésticos/crescimento & desenvolvimento , Cruzamento , Bovinos , Células Cultivadas , Primers do DNA/química , Distonia/congênito , Distonia/genética , Distonia/veterinária , Feminino , Perfilação da Expressão Gênica , Ligação Genética , Proteínas da Membrana Plasmática de Transporte de Glicina/genética , Humanos , Masculino , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Locos de Características Quantitativas , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Homologia de Sequência de AminoácidosRESUMO
A total of 678 individuals from 28 European bovine breeds were both phenotyped and analysed at the myostatin locus by the Single Strand Conformation Polymorphism (SSCP) method. Seven new mutations were identified which contribute to the high polymorphism (1 SNP every 100 bp) present in this small gene; twenty haplotypes were described and a genotyping method was set up using the Oligonucleotide Ligation Assay (OLA) method. Some haplotypes appeared to be exclusive to a particular breed; this was the case for 5 in the Charolaise (involving mutation Q204X) and 7 in the Maine-Anjou (involving mutation E226X). The relationships between the different haplotypes were studied, thus allowing to test the earlier hypothesis on the origin of muscular hypertrophy in Europe: muscular hypertrophy (namely nt821(del11)) was mainly spread in different waves from northern Europe milk purpose populations in most breeds; however, other mutations (mostly disruptive) arose in a single breed, were highly selected and have since scarcely evolved to other populations.
