RESUMEN
Women carrying a pathogenic mutation in either BRCA1 or BRCA2 have a major risk of developing breast and/or ovarian cancer. The majority of mutations in these genes are small point mutations. Since the development of multiplex ligation-dependent probe amplification, an increasing number of large genomic rearrangements have been detected. Here, we describe the characterization of pathogenic deletions of exons 1a-2 of BRCA1 in six families using loss of heterozygosity, array comparative genomic hybridization, and sequence analyses. Two families harbor a 37 kb deletion starting in intron 2 of psi BRCA1, encompassing NBR2, and exons 1a-2 of BRCA1, while the other four families have an 8 kb deletion with breakpoints in intron 2 of NBR2 and intron 2 of BRCA1. This observation, together with the previously described families with exon 1a-2 deletions of BRCA1, demonstrates that this type of deletions is relatively frequent in breast/ovarian cancer families.
Asunto(s)
Exones , Genes BRCA1 , Eliminación de Secuencia , Adulto , Neoplasias de la Mama/genética , Estudios de Cohortes , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Familia , Femenino , Marcadores Genéticos , Haplotipos , Humanos , Intrones , Pérdida de Heterocigocidad , Persona de Mediana Edad , Técnicas de Amplificación de Ácido Nucleico , Hibridación de Ácido Nucleico , Neoplasias Ováricas/genética , Linaje , Mutación Puntual , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
In this paper we describe the nucleotide sequence of a 3.4 kbp region of the Mycobacterium leprae genome. This region contains an open reading frame of 1290 bp with a coding capacity for a protein of 46,179 Da, designated the 38L protein. Using antibodies against part of the 38L protein, we were able to demonstrate that the 38L protein is present in the membrane protein fraction of M. leprae. The 38L protein showed significant matches with a number of integral membrane proteins involved in the transport of small molecules through the cellular membrane. Among these are a human and a murine protein involved in melanin biosynthesis. The 38L protein might play a role in the hypopigmentation observed in leprosy patients.