RESUMO
The melanocortin 1 receptor (Mc1r) is encoded by the Extension locus in many different mammals, where a loss-of-function causes exclusive production of red/yellow pheomelanin, and a constitutively activating mutation causes exclusive production of black/brown eumelanin. In the domestic dog, breeds with a wild-type E allele, e. g., the Doberman, can produce either pigment type, whereas breeds with the e allele, e.g., the Golden Retriever, produce exclusively yellow pigment. However, a black coat color in the Newfoundland and similar breeds is thought to be caused by an unusual allele of Agouti, which encodes the physiologic ligand for the Mc1r. Here we report that the predicted dog Mc1r is 317 residues in length and 96% identical to the fox Mc1r. Comparison of the Doberman, Newfoundland, Black Labrador, Yellow Labrador, Flat-coated Retriever, Irish Setter, and Golden Retriever revealed six sequence variants, of which two, S90G and R306ter, partially correlated with a black/brown coat and red/yellow coat, respectively. R306ter was found in the Yellow Labrador, Golden Retriever, and Irish Setter; the latter two had identical haplotypes but differed from the Yellow Labrador at three positions other than R306ter. In a larger survey of 194 dogs and 19 breeds, R306ter and a red/yellow coat were completely concordant except for the Red Chow. These results indicate that the e allele is caused by a common Mc1r loss-of-function mutation that either reoccurred or was subject to gene conversion during recent evolutionary history, and suggest that the allelic and locus relationships for dog coat color genes may be more analogous to those found in other mammals than previously thought.
Assuntos
Cães/genética , Variação Genética/genética , Cor de Cabelo/genética , Receptores da Corticotropina/genética , Alelos , Sequência de Aminoácidos , Animais , DNA/química , Primers do DNA/química , Cães/classificação , Genótipo , Dados de Sequência Molecular , Fenótipo , Filogenia , RNA/química , RNA/isolamento & purificação , Receptores de Melanocortina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
In addition to static brain images, cerebral radionuclide angiograms (CRAGs) were performed in 1,051 children to determine the value of routine radionuclide angiography. The CRAG resulted in a statistically significant increase in detection of abnormalities (p less than 0.01), as it provided the only evidence of confirmed abnormalities in 60 children (5.7%). The CRAG helped detect subdural fluid collections, cerebrovascular disease, and cerebral cysts, but it was of little value in detecting hydrocephalus. For maximum diagnostic yield, a CRAG should be performed with all pediatric brain-imaging studies.