29 research outputs found

    GWAS in Breast Cancer

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    Breast cancer is the most diagnosed cancer in women, and the second cause of cancer-related deaths among women worldwide. It is expected that more than 240,000 new cases and 40,450 deaths related to the disease will occur in 2016. It is well known that inherited genetic variants are drivers for breast cancer development. There are many mechanisms through which germline genetic variation affects prognosis, such as BRCA1 and BRCA2 genes, which account for approximately 20% of the increased hereditary risks. Therefore, it is evident that the genetic pathways that underlie cancer development are complex in which networks of multiple alleles confer disease susceptibility and risks. Global analyses through genome-wide association studies (GWAS) have revealed several loci across the genome are associated with the breast cancer. This chapter compiles all breast GWAS released since 2007, year of the first article published in this area, and discuss the future directions of this field. Currently, hundreds of genetic markers are linked to breast cancer, and understanding the underlying mechanisms of these variants might lead to the discover of biomarkers and targets for therapy in patients

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Carcinofauna bêntica estuarina de dois manguezais da costa amazônica maranhense, Brasil

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    RESUMO Este estudo teve por objetivo caracterizar a diversidade carcinológica de dois manguezais (igarapés Buenos Aires e Tronco) da Baía de São Marcos, na costa amazônica maranhense, Brasil. Foram realizadas quatro coletas trimestrais entre setembro de 2011 a junho de 2012. Em cada coleta foram analisados três pontos por área (zona 1, zona 2 e zona 3), totalizando 24 amostras. O material biológico foi coletado por meio de arrastos com rede do tipo puçá, catação manual e técnica de braceamento. Paralelamente à coleta do material biológico, foram verificados a salinidade, temperatura e oxigênio dissolvido de cada área analisada. Para avaliar a similaridade de agrupamento entre as zonas dos manguezais foi aplicada a análise de cluster e consecutiva elaboração de dendrogramas. Foi coletado um total de 873 indivíduos, representando nove famílias e 21 espécies, das quais Ocypodidae e Penaeidae foram as mais abundantes. Em relação à distribuição espacial, percebe-se que Clibanarius vittatus (Bosc, 1802), Clibanarius tricolor (Gibbes, 1850), Clibanarius foresti Holthuis, 1959 e Uca maracoani (Latreille, 1802) se restringiram à primeira zona dos dois manguezais, enquanto outras dez espécies foram observadas por todo o manguezal, o que pode estar intimamente relacionado ao seu hábito de vida. De um modo geral, o igarapé Buenos Aires apresentou maior número de espécies em relação ao igarapé Tronco, no entanto, existe grande similaridade faunística de crustáceos decápodes entre as duas áreas amostradas
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