Abstract Chromosomal Microarray Analysis (CMA) has increased the comprehension of the mechanisms of copy number variation (CNV) formation, classification of these rearrangements, type of recurrence, and its origin, and has also been a powerful approach to identifying CNVs in individuals with intellectual disability. The aim of this study was to establish the parental origin of de novo pathogenic CNV in a cohort of patients with intellectual disability from the public health system of Goiás-Brazil. CMA was done in 76 trios and we identified 15 de novo pathogenic CNVs in 12 patients with intellectual disability. In a total of 15 de novo pathogenic CNV, 60% were derived from the maternal germline and 40% from the paternal germline. CNV flanked by low copy repeats (LCR) were identified in 46.7% and most of them were of maternal origin. No significant association was observed between paternal age and the mutation rate of de novo CNVs. The presence of high-identity LCRs increases the occurrence of CNV formation mediated by non-allelic homologous recombination and the majority of paternal CNVs are non-recurrent. The mechanism of formation of these CNV may have been by microhomology-mediated break-induced replication or non-homologous end joining. (CMA (CNV rearrangements recurrence GoiásBrazil. GoiásBrazil Goiás Brazil. Brazil Goiás-Brazil 7 1 60 40 LCR (LCR 467 46 46.7 highidentity high identity nonallelic non allelic nonrecurrent. nonrecurrent recurrent. recurrent non-recurrent microhomologymediated microhomology breakinduced break induced nonhomologous joining 6 4 46.

O Aconselhamento Genético (AG) constitui um processo de investigação do diagnóstico de doenças genéticas. Este estudo de caso objetivou a análise de um modelo de AG. A coleta de dados foi realizada por meio de entrevista semiestruturada e da observação de uma sessão de AG. Os participantes foram profissionais biomédicos e a consulente de uma criança com diagnóstico de síndrome do duplo Y. Verificou-se que o AG envolve uma relação intersubjetiva complexa. Percebeu-se, nos dois polos da relação – profissional e consulente-familiar –, os aspectos emocionais (angústia, temor, culpas etc.) e defensivos (identificação, racionalização etc.) referidos na literatura das crises vitais. A análise do processo de AG indicou: 1) dissonância entre a teoria do AG e a ação do profissional; 2) fixação (defensiva) ao protocolo do AG; 3) uso de linguagem técnica dificultando contato e acolhimento do consulente; e, 4) tempo de compreender considerado na dimensão cronológica e não lógico. Infere-se que os fatores afetivos (angústia, temor, culpas etc.) e a defesa psíquica (identificação, racionalização) restringiram a comunicação do diagnóstico comprometendo o acolhimento e esclarecimento do contexto vital do consulente. Conclui-se que o modelo de AG poderia se enriquecer com a experiência do modelo de aconselhamento psicológico no que se refere ao manejo de crises vitais e no trabalho em equipes multidisciplinares.

Genetic Counseling (GC) comprises an investigation regarding the diagnosis of genetic diseases. Thus, this case study aimed to analyze a particular GC model. Data collection was conducted through semi-structured interviews and an observation of a GC session. The participants comprised professionals, a biomedical team, and a consultant for a child diagnosed with double Y syndrome. It was observed that GC involves a complex intersubjective relationship and that, in both ends of the relationship (i.e., professional consultants and family members), emotional factors (anxiety, fear, guilty, etc.) and defensiveness (identification, rationalization, etc.) restricted the communication of the diagnosis, preventing the host from effectively explaining such vital information to the inquirer. The GC review process also indicated the following four findings: 1) A dissonance between GC theory and professional actions, 2) A fixation on GC protocol, 3) The use of technical language that made it difficult to communicate, and 4) Insufficient time for considering the chronological dimension. On the basis of the findings, it can be concluded that the GC model could be enriched by the psychological counseling model, especially in relation to crisis management and the vital work of multidisciplinary teams.

El Asesoramiento Genético (AG) constituye un proceso de investigación del diagnóstico de enfermedades genéticas. Este estudio de caso tuvo como objetivo analizar un modelo de AG. La colecta de datos fue realizada por medio de entrevista semiestructurada y de la observación de una sesión de AG. Los participantes fueron profesionales biomédicos y el consultante de un niño con diagnóstico de síndrome del doble Y. Se verificó que el AG implica una relación intersubjetiva compleja. Se percibió, en los dos polos de la relación – profesional y consultante – familiar –, los aspectos emocionales (angustia, temor, culpas, etc.) y defensivos (identificación, racionalización etc.) mencionados en la literatura como crisis vitales. El análisis del proceso de AG indicó: 1) disonancia entre la teoría del AG y la acción del profesional; 2) fijación (defensiva) al protocolo del AG, 3) uso de lenguaje técnico dificultando contacto y acogimiento del consultante; e, 4) tiempo de comprender considerado en la dimensión cronológica y no lógica. Se infiere que los factores afectivos (angustia, temor, culpas, etc) y la defensa psíquica (identificación, racionalización) restringieron la comunicación del diagnóstico comprometiendo el acogimiento y aclaratoria del contexto vital del consultante. Se concluye que el modelo de AG podría enriquecerse con la experiencia del modelo de asesoramiento psicológico en lo que se refiere al manejo de crisis vitales y en el trabajo en equipos multidisciplinarios.

O objetivo desta revisão bibliográfica foi descrever a epidemiologia, o comportamento biológico dos tumores e os fatores de risco para o câncer de pênis, como a infecção pelo HPV. A fimose e os processos de irritação crônica relacionados à má higiene estão comumente associados com esse tumor, enquanto a circuncisão neonatal protege contra a aparição da doença. Existe forte evidência da associação dos HPV 16 e 18 com o carcinoma peniano em mais de 50% dos casos. Pacientes com lesões penianas suspeitas devem se submeter ao exame físico, geralmente sendo este suficiente para determinar o diagnóstico e o estadiamento, assim como auxiliar na escolha terapêutica.

The general objective of this article is to review the current literature regarding the epidemiology, biological behavior and risk factors for penile cancer development, such as HPV infection. Phimosis and chronic irritation related to poor hygiene are commonly associated with penile cancer, whereas neonatal circumcision reduces the relative risk for the disease. There is strong evidence that HPV types 16 and 18 are associated with penile carcinoma in as many as 50% of cases. Patients with penile lesions should undergo physical examination, which is often sufficient to diagnose and to define tumor stagging, as well as contributes to decision-making regarding therapeutical approaches and case management.

O objetivo desta revisão bibliográfica foi descrever a epidemiologia, o comportamento biológico dos tumores e os fatores de risco para o câncer de pênis, como a infecção pelo HPV. A fimose e os processos de irritação crônica relacionados à má higiene estão comumente associados com esse tumor, enquanto a circuncisão neonatal protege contra a aparição da doença. Existe forte evidência da associação dos HPV 16 e 18 com o carcinoma peniano em mais de 50% dos casos. Pacientes com lesões penianas suspeitas devem se submeter ao exame físico, geralmente sendo este suficiente para determinar o diagnóstico e o estadiamento, assim como auxiliar na escolha terapêutica.

The general objective of this article is to review the current literature regarding the epidemiology, biological behavior and risk factors for penile cancer development, such as HPV infection. Phimosis and chronic irritation related to poor hygiene are commonly associated with penile cancer, whereas neonatal circumcision reduces the relative risk for the disease. There is strong evidence that HPV types 16 and 18 are associated with penile carcinoma in as many as 50% of cases. Patients with penile lesions should undergo physical examination, which is often sufficient to diagnose and to define tumor stagging, as well as contributes to decision-making regarding therapeutical approaches and case management.

O objetivo do presente estudo foi avaliar a aplicabilidade de uma cartilha educativa, que abordou informações de interesse da população para a promoção e prevenção de infecções e neoplasias ocasionadas pelo papilomavírus humano (HPV). O estudo foi realizado em duas etapas. Na primeira, a cartilha educativa foi aplicada a duzentos voluntários, na cidade de Goiânia (GO), de ambos os sexos, com nível de escolaridade variando do ensino médio ao superior. A aplicabilidade da cartilha foi avaliada sem a necessidade de conhecimento prévio dos participantes sobre o HPV. Os participantes responderam a um questionário para a avaliação da cartilha. Na segunda etapa, foi feita uma análise detalhada dos dados, e a cartilha mostrou-se aplicável. Posteriormente, o material didático foi publicado e 2.000 exemplares foram distribuídos gratuitamente em um evento de ação social realizado pela Pontifícia Universidade Católica de Goiás, na cidade de Goiânia. No evento, a cartilha despertou o interesse dos participantes por informações adicionais e propiciou aos voluntários a oportunidade de participar de um estudo para a investigação da presença de HPV como microbiota genital. A cartilha demonstrou-se aplicável e atingiu o seu objetivo de informação e prevenção. É necessário promover campanhas de conscientização da população sobre o HPV e sua relação com as neoplasias malignas.

The present study aimed to evaluate the applicability of an educational booklet that contained information for the general population about promotion and prevention of infections and neoplasic process caused by the human papillomavirus (HPV). The study was arranged in two phases. First, the booklet was given to 200 volunteers in the city of Goiânia, Goiás State. The applicability of the booklet was evaluated without the necessity of proving former knowledge. In the second phase, a detailed analysis of the data was made and the booklet revealed applicable. Then, the educational material was published and 2000 copies were distributed in a social event held by the Pontifícia Universidade Católica de Góias in the city of Goiânia. In the event, the booklet raised the interest of the general public and gave the volunteers a chance to participate in a study that investigated the presence of the HPV in the genital microbiote. The booklet proved to be applicable and reached its objective to inform and prevent. However, it's necessary to promote and improve campaigns to the population about the HPV and its relations with the neoplasic process.

O objetivo do presente estudo foi avaliar a aplicabilidade de uma cartilha educativa, que abordou informações de interesse da população para a promoção e prevenção de infecções e neoplasias ocasionadas pelo papilomavírus humano (HPV). O estudo foi realizado em duas etapas. Na primeira, a cartilha educativa foi aplicada a duzentos voluntários, na cidade de Goiânia (GO), de ambos os sexos, com nível de escolaridade variando do ensino médio ao superior. A aplicabilidade da cartilha foi avaliada sem a necessidade de conhecimento prévio dos participantes sobre o HPV. Os participantes responderam a um questionário para a avaliação da cartilha. Na segunda etapa, foi feita uma análise detalhada dos dados, e a cartilha mostrou-se aplicável. Posteriormente, o material didático foi publicado e 2.000 exemplares foram distribuídos gratuitamente em um evento de ação social realizado pela Pontifícia Universidade Católica de Goiás, na cidade de Goiânia. No evento, a cartilha despertou o interesse dos participantes por informações adicionais e propiciou aos voluntários a oportunidade de participar de um estudo para a investigação da presença de HPV como microbiota genital. A cartilha demonstrou-se aplicável e atingiu o seu objetivo de informação e prevenção. É necessário promover campanhas de conscientização da população sobre o HPV e sua relação com as neoplasias malignas.

The present study aimed to evaluate the applicability of an educational booklet that contained information for the general population about promotion and prevention of infections and neoplasic process caused by the human papillomavirus (HPV). The study was arranged in two phases. First, the booklet was given to 200 volunteers in the city of Goiânia, Goiás State. The applicability of the booklet was evaluated without the necessity of proving former knowledge. In the second phase, a detailed analysis of the data was made and the booklet revealed applicable. Then, the educational material was published and 2000 copies were distributed in a social event held by the Pontifícia Universidade Católica de Góias in the city of Goiânia. In the event, the booklet raised the interest of the general public and gave the volunteers a chance to participate in a study that investigated the presence of the HPV in the genital microbiote. The booklet proved to be applicable and reached its objective to inform and prevent. However, it's necessary to promote and improve campaigns to the population about the HPV and its relations with the neoplasic process.

A leucemia mielóide crônica (LMC) é uma doença proliferativa do sistema hematopoiético, caracterizada pela expansão clonal de uma célula-tronco primitiva e pluripotente denominada stem cell. Este tipo de leucemia está associado, em 90% dos casos, à translocação t(9;22)(q34;q11). Essa alteração cromossômica estrutural codifica para uma proteína quimérica BCR-ABL, que confere às células leucêmicas uma alta resistência à morte, independente do agente indutor desse processo. A proteína p53 é uma reguladora transcricional induzida por danos no DNA, fato que resulta na parada do ciclo celular com conseqüente ativação de mecanismos de reparo ou mesmo na indução à apoptose. As mutações no gene TP53 são as alterações genéticas mais comuns em tumores malignos humanos. O presente estudo teve como objetivo genotipar e determinar a freqüência alélica do polimorfismo do TP53 no códon 72 (arginina - Arg e prolina - Pro), em pacientes com suspeita de LMC, pela Reação em Cadeia da Polimerase. Desta forma, os resultados indicaram que 73,4% (23/30) dos pacientes apresentaram homozigose para arginina (Arg/Arg) e 26,6% (7/30) heterozigose (Arg/Pro). Não foi encontrado nenhum paciente homozigoto para prolina (Pro/Pro). Os resultados obtidos sugerem que o polimorfismo do gene TP53 no códon 72 não é um fator de risco importante para a iniciação, promoção e progressão da LMC.

Chronic myeloid leukemia (CML) is a proliferative disorder of the hematopoietic system characterized by clonal expansion of a primitive and pluripotent stem cell. In this type of leukemia, up to 90% of all cases is associated to a specific chromosomal translocation, t(9;22)(q34;q11). The genomic alteration results in a chimeric protein, BCR-ABL, that confers a high resistance leukemia cells to death, independent of the induction mechanism of this process. Protein p53 is a transcriptional factor expressed after DNA damage which ceases cell cycle progression and consequently activates repair mechanisms or even induces apoptosis. Mutations of TP53 are the most common genetic alterations in malignant tumors in humans. The main objective of the current study was to genotype and determine the allelic frequency of the TP53 polymorphism at codon 72 in patients suspected of having CML using a PCR-based assay. The frequencies of the genotypes among the cases were: 73.4% (23\30) and 26% (7\30) for homozygous arginine (Arg-72) and heterozygous proline/arginine (Pro/Arg-72), respectively. Homozygous proline (Pro-72) was not observed in the current study. The results obtained suggest that the TP53 polymorphism at codon 72 is not an important risk factor for the initiation, promotion, nor progression of CML.

This study reports on 156 specimens of the amphibian Eupemphix nattereri, a widely distributed leiuperid, obtained from 11 municipalities of central Brazil. The extent of genetic variation was quantified by determining the mean number of alleles per locus and the proportion of polymorphic loci. An analysis of molecular variance (AMOVA) was performed on the random amplified polymorphic DNA (RAPD) haplotypes. The genetic distances obtained by calculating pairwise phist among local samples were used to determine population relationships using the unweighted pair-group method (UPGMA) and non-metric multidimensional scaling (NMDS). The cophenetic correlation was calculated to confirm agreement between the genetic matrix and the unweighted pair group method with averages (UPGMA) dendrogram. To determine if genetic distances were correlated to geographical distances we constructed pairwise genetic distance and geographical distance matrices and compared them using the Mantel test. The AMOVA results indicated significant genetic differences (p < 0.001) between E. nattereri populations, representing 69.5% of the within population genetic diversity. The Mantel test showed no significant correlation (r = 0.03; p = 0.45) between the genetic and geographical distance matrices. Our findings indicate that the genetic variation of E. nattereri populations was randomly distributed in geographic space and that gene flow for this species is probably structured at spatial scales smaller than those between our samples

The TK6 lymphoblastoid cell line is known to be mismatch repair (MMR) and p53 proficient. Deficiency in MMR results in a mutator phenotype characterized by microsatellite instability (MSI) and increased hprt mutant frequency (MF). Increased hprt MF is also a biomarker of effect for exposure to ionizing radiation. In order to test if a mutator phenotype could be induced by low doses of gamma ionizing radiation, an hprt cloning assay and a MSI investigation were performed after radiation exposure. The spontaneous MF was 1.6 x 10-6. The groups exposed to 0.2, 0.5 and 1.0 Gy had hprt MFs of 2.3, 3.3 and 2.2 x 10-6, respectively. The spontaneous MSI frequency per allele in non-selected cells was 5.4 x 10-3, as evidenced at the loci D11S35, nm23-H1, D8S135 and p53. MSI frequencies in the groups exposed to 0.2, 0.5 and 1.0 Gy were found to be < 4.7, < 7.7 and < 12 x 10-3, respectively. The frequencies of hprt mutants and MSI found in this study suggest that low doses of ionizing radiation increase hprt mutant frequency without triggering the mutator phenotype pathway.

The multisteps of tumorigenesis involve the classic chromosomal instability and the mutator phenotype pathways featured by a predisposition to acquire mutations in tumor suppressor genes and oncogenes. Expansion and contraction of microsatellite sequences due to a deficient mismatch repair system are a marker of the mutator phenotype. Controversial results regarding the extent of microsatellite instability (MSI) have been reported in the development and progression of myeloid malignancies. Here, we investigated MSI and loss of heterozygosity (LOH) frequencies at the microsatellite loci BAT-26, D7S486, D8S135, ANK1, IFNA, TP53 and bcr of 19 Brazilian patients with acute (AML) and chronic myeloid leukemia (CML). One AML patient and one CML patient were categorized as having a high degree of microsatellite instability (MSI-H), corresponding to 10.5% (2/19) of all patients. LOH at loci BAT-26 and TP53 was present in 30% of the patients with AML alone. Despite the small sample size, our results suggest that the mutator phenotype, as verified by MSI frequency, could play a role in the leukemogenesis of a small subset of patients with myeloid leukemia.