RESUMEN
We present measurements of ν(µ) charged-current cross section ratios on carbon, iron, and lead relative to a scintillator (CH) using the fine-grained MINERvA detector exposed to the NuMI neutrino beam at Fermilab. The measurements utilize events of energies 2
RESUMEN
BACKGROUND: BRCA1 is a tumour suppressor with pleiotropic actions. Germline mutations in BRCA1 are responsible for a large proportion of breast-ovarian cancer families. Several missense variants have been identified throughout the gene but because of lack of information about their impact on the function of BRCA1, predictive testing is not always informative. Classification of missense variants into deleterious/high risk or neutral/low clinical significance is essential to identify individuals at risk. OBJECTIVE: To investigate a panel of missense variants. METHODS AND RESULTS: The panel was investigated in a comprehensive framework that included (1) a functional assay based on transcription activation; (2) segregation analysis and a method of using incomplete pedigree data to calculate the odds of causality; (3) a method based on interspecific sequence variation. It was shown that the transcriptional activation assay could be used as a test to characterise mutations in the carboxy-terminus region of BRCA1 encompassing residues 1396-1863. Thirteen missense variants (H1402Y, L1407P, H1421Y, S1512I, M1628T, M1628V, T1685I, G1706A, T1720A, A1752P, G1788V, V1809F, and W1837R) were specifically investigated. CONCLUSIONS: While individual classification schemes for BRCA1 alleles still present limitations, a combination of several methods provides a more powerful way of identifying variants that are causally linked to a high risk of breast and ovarian cancer. The framework presented here brings these variants nearer to clinical applicability.
Asunto(s)
Neoplasias de la Mama/genética , Genes BRCA1 , Mutación Missense , Neoplasias Ováricas/genética , Adolescente , Adulto , Algoritmos , Proteína BRCA1/química , Proteína BRCA1/clasificación , Proteína BRCA1/metabolismo , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Estructura Terciaria de Proteína , Activación TranscripcionalRESUMEN
The signal flow diagram is a graphic method used to represent complex data that is found in the field of biology and hence the field of medicine. The signal flow diagram is analyzed against a table of data and a flow chart of data and evaluated on the clarity and simplicity of imparting this information. The data modeled is from previous clinical studies and nontraditional medicine from Africa, China, and South America. This report is a development from previous presentations of the signal flow diagram.1-4