RESUMO
Genome-wide association studies (GWASes) have become a powerful tool for identifying genomic regions associated with important traits in livestock. Milk production traits in dairy sheep are measured at different time points during their life span. Using phenotypic data generated from longitudinal traits could improve the power of association studies but until now have received less attention in GWASes as a methodology and has not been implemented. The aim of this study was to carry out a GWAS for milk production traits in Valle del Belice sheep using repeated measures. After quality control, 469 ewes and 37 228 SNPs were retained for the analysis, and phenotypic data included 5586 test-day records for five milk production traits (milk yield, MY; fat yield and percentage, FY and F%; protein yield and percentage, PY and P%). Nine SNPs located within or close to known genes were found to be associated with milk production traits. In particular, rs398340969, associated with both milk yield and protein yield, is located within the DCPS gene. In addition, rs425417915 and rs417079368, both associated with both fat percentage and protein percentage, are located within the TTC7B gene and at 0.37 Mb within the SUCNR1 gene respectively. In summary, the use of repeated records was beneficial for mapping genomic regions affecting milk production traits in the Valle del Belice sheep.
Assuntos
Estudo de Associação Genômica Ampla/veterinária , Leite , Carneiro Doméstico/genética , Carneiro Doméstico/fisiologia , Animais , Feminino , Polimorfismo de Nucleotídeo Único , Carneiro Doméstico/classificaçãoRESUMO
Microtia is a congenital deformity of the outer ear with phenotypes varying from a small auricle to total absence (anotia). The genetic basis is still poorly understood, and very few studies have been performed in sheep. Valle del Belice sheep is a breed showing microtia. The aim of this study was to identify the potential genomic regions involved in microtia in sheep. A total of 40 individuals, 20 with microtia and 20 normal, were genotyped with the Illumina OvineSNP50 BeadChip. The comparison among the results from a genome-wide association study, Fisher's exact test and FST analysis revealed a single strong association signal: rs419889303 on chromosome 1, located within intron 3 of the CLRN1 gene. Our study suggests for the first time that this novel candidate gene is responsible for microtia in sheep. Additional analysis based on the sequencing would help confirm our findings and allow for the proposal of a precise genetic basis for microtia in sheep.
Assuntos
Microtia Congênita/genética , Proteínas de Membrana/genética , Doenças dos Ovinos/genética , Carneiro Doméstico/genética , Animais , Cruzamento , Estudos de Associação Genética/veterinária , Genótipo , Polimorfismo de Nucleotídeo Único , OvinosRESUMO
INTRODUCTION: SIOPEN INES protocol yielded excellent 5-year survival rates for MYCN-non-amplified metastatic neuroblastoma. Patients deemed ineligible due to lack or delay of MYCN status or late registration were treated, but not included in the study. Our goal was to analyse survival at 10 years among the whole population. MATERIALS AND METHODS: Italian and Spanish metastatic INES patients' data are reported. SPSS 20.0 was used for statistical analysis. RESULTS: Among 98 infants, 27 had events and 19 died, while 79 were disease free. Five- and 10-year event-free survival (EFS) were 73 and 70 %, and overall survival (OS) was 81 and 74 %, respectively. MYCN status was significant for EFS, but not for OS in multivariate analysis. CONCLUSIONS: The survival rates of patients who complied with all the inclusion criteria for INES trials are higher compared to those that included also not registered patients. Five-year EFS and OS for INES 99.2 were 87.8 and 95.7 %, while our stage 4s population obtained 78 and 87 %. Concerning 99.3, 5-year EFS and OS were 86.7 and 95.6 %, while for stage 4 we registered 61 and 68 %. MYCN amplification had a strong impact on prognosis and therefore we consider it unacceptable that many patients were not studied for MYCN and probably inadequately treated. Ten-year survival rates were shown to decrease: EFS from 73 to 70 % and OS from 81 to 74 %, indicating a risk of late events, particularly in stage 4s. Population-based registries like European ENCCA WP 11-task 11 will possibly clarify these data.
Assuntos
Biomarcadores Tumorais/genética , Ensaios Clínicos como Assunto , Amplificação de Genes , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estadiamento de Neoplasias , Neuroblastoma/genética , Neuroblastoma/secundário , Neuroblastoma/terapia , Prognóstico , Taxa de SobrevidaRESUMO
The aim of this work was to sequence the promoter region of ß-lactoglobulin (BLG) gene in four sheep breeds, in order to identify polymorphisms, infer and analyze haplotypes, and phylogenetic relationship among the Valle del Belice breed and the other three breeds considered as ancestors. Sequencing analysis and alignment of the obtained sequences showed the presence of 36 single nucleotide polymorphisms (SNPs) and one deletion. A total of 22 haplotypes found in "best" reconstruction were inferred considering the 37 polymorphic sites identified. Haplotypes were used for the reconstruction of a phylogenetic tree using the Neighbor-Joining algorithm. The number of polymorphisms identified showed high variability within breeds. Analysis of genetic diversity indexes showed that the Sarda breed presented the lowest nucleotide diversity, whereas the Comisana breed presented the highest one. Comparing the nucleotide diversity among breeds, the highest value was obtained between Valle del Belice and Pinzirita breeds, whereas the lowest one was between Valle del Belice and Sarda breeds. Considering that polymorphisms in the promoter region of BLG gene could have a functional role associated with milk composition, the lowest value of nucleotide diversity between Valle del Belice and Sarda breeds may be related to a higher similarity of milk composition of these two breeds compared to the others. Further analyses will be conducted in order to evaluate the possible correlation between the genetic diversity indexes and the BLG content in milk of our breeds.