RESUMEN
The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2. This yielded a prevalence rate of 14.4%. Seven recurrent variants were found accounting for 55% of the cases. Among them, three are widely distributed (BRCA1 c.211A>G, c.470_471del and c.3331_3334del) and four had been reported as novel in Asturias: two in BRCA1 (c.1674del and c.2901_2902dup) and two in BRCA2 (c.2095C>T and c.4040_4035delinsC). A common haplotype was established for all recurrent variants indicating a shared ancestral origin. Three splicing analyses are shown: BRCA1:c.5152+3A>C and BRCA1:c.5333-3T>G that lead to skipping of exon 18, and 22 respectively, and BRCA1:c.5278-1G>T giving rise to two transcripts, one lacking exon 21 (p.Ille1760Glyfs*60) and one lacking the first 8 nucleotides of exon 21 (p.Phe1761Asnfs*14), supporting pathogenicity for these variants.
Asunto(s)
Proteína BRCA1 , Proteína BRCA2 , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Humanos , Mutación de Línea Germinal/genética , España/epidemiología , Proteína BRCA1/genética , Femenino , Proteína BRCA2/genética , Adulto , Persona de Mediana Edad , Haplotipos/genética , Linaje , Exones/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , MasculinoAsunto(s)
Trastornos Mieloproliferativos/genética , Receptores del Factor Estimulante de Colonias/genética , Translocación Genética , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 9 , Dasatinib/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Trastornos Mieloproliferativos/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Nitrilos , Pirazoles/uso terapéutico , PirimidinasAsunto(s)
Cromosomas Humanos Par 12 , Proteína ETS de Variante de Translocación 6 , Leucemia Mieloide Aguda , Proteínas de Fusión Oncogénica , Proteínas Proto-Oncogénicas c-ets , Proteínas Represoras , Translocación Genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Proteínas de Fusión Oncogénica/genética , Proteínas Represoras/genética , Cromosomas Humanos Par 12/genética , Proteínas Proto-Oncogénicas c-ets/genética , Cromosomas Humanos Par 7/genética , Recién Nacido , Lactante , Factores de Transcripción/genética , Masculino , Femenino , Proteína del Locus del Complejo MDS1 y EV11RESUMEN
Proteases constitute up to 3% of all protein-coding genes in a vertebrate genome and participate in numerous physiological and pathological processes. The characterization of the degradome of one organism, the set of all genes encoding proteolytic enzymes, and the comparison to the degradome of other species have proved useful to identify genetic differences that are helpful to elucidate the molecular basis of diverse biological processes, the different susceptibility to disease, and the evolution of the structure and function of proteases. Here we describe the main procedures involved in the characterization of the degradome of an organism for which its genome sequence is available.