RESUMEN
Abstract Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaβ pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaβ pathway in predisposition to endometriosis.
RESUMEN
Yerba mate (Ilex paraguariensis A. St.-Hil.: Aquifoliaceae) is the basis for a hot drink very common in southern Brazil and other countries such as Argentina, Paraguay and Uruguay: the mate. However, the available data about its effect on DNA are still controversial. In this research, we evaluated the mutagenic and antimutagenic activity of mate with the Allium cepa assay, analyzing the frequency of micronucleus (MN), cromossomal aberrations (CA) and the mitotic index (MI) from treatments with mate only and treatments with mate and the positive control Methyl Methanesulfonate (MMS) being administered previously, simultaneously and subsequently. Mate itself did not show mutagenic potential. However, the protocols which MMS was administered simultaneously and subsequently, it potentiated the mutagenic effect of the drug. There was no significant increase in the previous treatment with MMS, indicating that there wasn?t a positive or negative influence of the mate on the DNA repair system and other mechanisms for reversing damage on meristematic cells of Allium cepa. Therefore, our results suggests that substances present in mate can act potentiating mutagenic and carcinogenic agents present in other compounds or perhaps damaging cells barriers from certain substances that harm the genetic material.
A erva-mate (Ilex paraguariensis A. St.-Hil.: Aquifoliaceae) é a base de uma bebida quente muito comum no sul do Brasil e em outros países tais como Argentina, Paraguai e Uruguai. No entanto, os dados disponíveis sobre seu efeito no DNA são ainda controversos. Nesta pesquisa, nós avaliamos a atividade mutagênica e antimutagênica do mate no sistema teste de Allium cepa, analisando a frequência de micronúcleos (MN), aberrações cromossômicas (CA) e o índice mitótico (MI) de tratamentos somente com mate e tratamentos com mate e o controle positivo Metil Metano Sulfonase (MMS) sendo administrado anteriormente, simultaneamente e posteriormente. O mate sozinho não apresentou potencial mutagênico. Porém, nos protocolos com MMS sendo administrados simultaneamente e posteriormente, o mate potencializou o efeito mutagênico da droga. Não houve aumentos significativos nos protocolos de tratamento anterior com MMS, indicando que não houve uma influência positiva ou negativa do mate no sistema de reparo de DNA ou outros mecanismos de reversão dos danos nas células meristemáticas da cebola. Desta forma, nossos resultados sugerem que substâncias presentes no mate podem agir potencializando agentes mutagênicos e carcinogênicos presentes em outros compostos ou talvez possam danificar as barreiras celulares a certos compostos que agridem o material genético.