RESUMEN
Recently, a new genetically autosomal recessive color phenotype emerged in the red pied bovine Montbéliarde breed. It is characterized by a dilution of the red areas of the coat and was denominated 'milca'. A genome-wide homozygosity scan of 106 cases followed by haplotype analysis revealed a candidate region within BTA2 between positions 89.95 and 91.63 Mb. Analysis of whole-genome sequence data generated from milca animals identified a strong candidate variant within the coding region of the Frizzled-7 gene (FZD7). This gene encodes for a G-protein coupled receptor for Wnt signaling proteins. The variant induces a glycine to alanine substitution in the second extracellular loop, p.(Gly414Ala). Cross-species amino acid alignments revealed that this glycine is conserved among orthologs and most paralogs, suggesting that it plays an important role in FZD function. In addition, genotyping data revealed that the mutant allele is restricted to the Montbéliarde breed, at a 3.7% frequency. All homozygous cows for the mutant allele exhibited the milca phenotype whereas all heterozygotes had no coat color defects. In conclusion, this study strongly suggests that, in cattle, a mutation of FZD7 alone is sufficient to cause a coat color phenotype without any strong other adverse effect.
Asunto(s)
Bovinos/genética , Receptores Frizzled/genética , Color del Cabello/genética , Mutación Missense , Alelos , Animales , FenotipoRESUMEN
In humans, the clinical and molecular characterization of sporadic syndromes is often hindered by the small number of patients and the difficulty in developing animal models for severe dominant conditions. Here we show that the availability of large data sets of whole-genome sequences, high-density SNP chip genotypes and extensive recording of phenotype offers an unprecedented opportunity to quickly dissect the genetic architecture of severe dominant conditions in livestock. We report on the identification of seven dominant de novo mutations in CHD7, COL1A1, COL2A1, COPA, and MITF and exploit the structure of cattle populations to describe their clinical consequences and map modifier loci. Moreover, we demonstrate that the emergence of recessive genetic defects can be monitored by detecting de novo deleterious mutations in the genome of bulls used for artificial insemination. These results demonstrate the attractiveness of cattle as a model species in the post genomic era, particularly to confirm the genetic aetiology of isolated clinical case reports in humans.
Asunto(s)
Estudios de Asociación Genética , Ganado/genética , Mutación , Fenotipo , Animales , Bovinos , Análisis Mutacional de ADN , Modelos Animales de Enfermedad , Enfermedades Genéticas Congénitas , Predisposición Genética a la Enfermedad , Genómica/métodos , Humanos , Linaje , Secuenciación Completa del GenomaRESUMEN
An immuno-allergological study was performed on 30 atopic patients and the data were compared to those of 30 healthy controls. The findings were: --increased level of IgE class immunoglobulins in the atopic patients; --increased frequency of the presence of specific reagin to numerous allergens in the sera of atopics (RAST). The total amount of IgE was related to the presence of numerous and/or strongly positive RAST; --immediate hypersensitivity reaction (IHR) to various allergens and specially house-dust. No well-definite correlation was found between IHR and RAST for the same allergens and between the in vitro determination of allergens and a known history of clinical provocation by these allergens. The frequency of positive IHR was related with high level of total IgE; --decreased frequency of delayed cutaneous hypersensitivity tests and specially of those with candidin extracts. Cutaneous hyporeactivity to natural antigens was in relation with high level of total IgE; --no significant statistical difference was found between the amount of T and B lymphocytes; --increased frequency of HLA-A2 group and decreased frequency of HLA-B7 group.