Avances en el diagnóstico de la enfermedad granulomatosa crónica: primer estudio familiar en Cuba / Advances in the diagnosis of chronic granulomatous disease: the first family study in Cuba

Introducción: La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en la enzima NADPH oxidasa. Esta compromete la producción de especies reactivas del oxígeno, que son importantes contra patógenos. La prueba de la oxidación de la dihidrorodamina es un método eficaz para diagnosticar la enfermedad. Objetivo: Demostrar la utilidad de la prueba de la oxidación de la dihidrorodamina y del patrón de herencia en la confirmación del diagnóstico de la enfermedad granulomatosa crónica de un paciente. Métodos: Estudio de caso de una familia con diagnóstico de enfermedad granulomatosa crónica. Se tomó muestra de sangre periférica para citometría de flujo a tres individuos. Se realizó la prueba de la oxidación de la dihidrorodamina bajo estímulo con acetato de forbolmiristato y se evaluaron las subpoblaciones linfocitarias. Las muestras se leyeron en un citómetro GALLIOS, Beckman Coulter. Los datos obtenidos se analizaron en el programa informático Kaluza. Resultados: El paciente masculino tuvo un valor de oxidación de la dihidrorodamina positiva de 0,87 por ciento, que confirmó un patrón de herencia ligado al cromosoma X; mientras que la madre y hermana gemela portadoras tuvieron valores de 46,76 por ciento y 37,32 por ciento, respectivamente. Se encontraron alteraciones en las subpoblaciones linfocitarias. Conclusiones: La prueba de la oxidación de la dihidrorodamina es un método muy efectivo, rápido y sencillo que confirma el diagnóstico de la enfermedad granulomatosa crónica y determina el patrón de herencia y fenotipo de la enfermedad. Además, permite identificar a las mujeres portadoras según la distribución de los neutrófilos normales y los que tienen el gen CYBB mutado(AU)

Introduction: Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the NADPH oxidase enzymes. This compromises the production of oxygen reactive species, which are important against pathogens. The dihydrorhodamine oxidation test is an effective method for diagnosing the disease. Objective: To demonstrate the usefulness of the dihydrorhodamine oxidation test and the inheritance pattern in confirming the diagnosis of chronic granulomatous disease in a patient. Methods: A case study of a family with a diagnosis of chronic granulomatous disease. A peripheral blood sample was taken from three individuals and by flow cytometry. The dihydrorhodamine oxidation test was performed under stimulation with phorbolmyristate acetate, and lymphocyte subpopulations were evaluated. The samples were read on a GALLIOS, Beckman Coulter cytometer. The data obtained were analyzed using the computer program Kaluza. Results: The male patient had a positive dihydrorhodamine oxidation value of 0.87 percent, which confirmed an inheritance pattern linked to the X chromosome; while the carrier mother and twin sister had values 8203;8203;of 46.76 percent and 37.32 percent, respectively. Alterations were found in the lymphocyte subpopulations. Conclusions: The dihydrorhodamine oxidation test is a very effective, fast and simple method that confirms the diagnosis of chronic granulomatous disease and determines the inheritance pattern and phenotype of the disease. In addition, it allows the identification of female carriers according to the distribution of normal neutrophils and those with the CYBB mutation(AU)

Reproductive alternatives for patients with dystrophic epidermolysis bullosa / Opções reprodutivas para pacientes com epidermólise bolhosa distrófica

ABSTRACT Epidermolysis bullosa describes a group of skin conditions caused by mutations in genes encoding proteins related to dermal-epidermal adhesion. In the United States, 50 cases of epidermolysis bullosa per 1 million live births are estimated, 92% of which classified as simplex, 5% dystrophic, 1% junctional and 2% non-classified. Dystrophic epidermolysis bullosa is associated with autosomal, dominant and recessive inheritance. Epidermolysis bullosa causes severe psychological, economic and social impacts, and there is currently no curative therapy, only symptom control. Embryonic selection is available for epidermolysis bullosa patients in order to prevent perpetuation of the condition in their offspring.

RESUMO O termo "epidermólise bolhosa" descreve um grupo de afecções cutâneas causadas por mutações em genes que codificam proteínas relacionadas à aderência dermoepidérmica. Nos Estados Unidos, estima-se a ocorrência de 50 casos de epidermólise bolhosa por 1 milhão de nascidos vivos, sendo 92% deles da forma simples, 5% da forma distrófica, 1% da forma juncional e 2% não classificados. A epidermólise bolhosa do tipo distrófica foi associada a padrões autossômicos, dominante e recessivo. A epidermólise bolhosa causa sérios impactos psicológicos, econômicos e sociais, e não há tratamento curativo atualmente − apenas controle dos sintomas. A seleção embrionária é disponível para portadores de epidermólise bolhosa, a fim de evitar a perpetuação da condição em seus descendentes.

Inimigas da pátria: Propostas educativas para a guerra contra as doenças venéreas na Marinha do Brasil nas décadas de 1920 e 1930 / Homeland enemies: Educational proposals for the war against venereal diseases in the Brazilian Navy in the 1920s and 1930s / Enemigas de la patria: Propuestas educativas para la guerra contra las enfermedades venéreas en la Marina de Brasil en las décadas de 1920 y 1930

Resumo Este artigo oferece reflexões preliminares acerca de propostas educativas voltadas ao combate das doenças venéreas na Marinha de Guerra divulgadas em duas obras de médicos militares nas décadas de 1920 e 1930 no Brasil: Doenças no Mundo (1923), de autoria do médico e capitão-de-corveta João Pires Porto-Carrero, e Moléstias Venéreas na Marinha brasileira (1933), escrito pelo médico e capitão-de-mar-e-guerra Artur do Valle Lins. Para tanto, a análise desdobrou-se em dois aspectos centrais: os debates nacionais acerca das doenças venéreas como empecilhos à construção da nação brasileira, e a presença destes nas propostas educativas divulgadas nos livros produzidos por médicos militares que tematizaram o combate às doenças venéreas na Força Naval brasileira. Por meio da análise dessas publicações pôde-se perceber uma íntima relação entre eugenia, sanitarismo e a luta contra tais doenças em meio a um projeto de construção da nação brasileira, algo que não esteve presente somente nas propostas educativas do exército, mas perpassou os debates nacionais da área médica.

Abstract This article offers preliminary reflections about educational proposals aimed at the combat of venereal diseases in the Navy, disseminated in two works by military doctors in the 1920s and 1930s in Brazil: Diseases in the World (1923), by the doctor and Captain-of-Corvette João Pires Porto-Carrero, and Venereal Diseases in the Brazilian Navy (1933), written by the doctor and Captain-of-Sea-and-War Artur do Valle Lins. The analysis focuses on two central aspects: the national debates about venereal diseases as obstacles to the construction of a Brazilian nation, and their presence in educational proposals presented in books produced by military doctors about the fight against venereal diseases in the Brazilian Naval Force. Through the analysis of these publications, it was possible to notice an intimate relationship between eugenics, sanitarism and the fight against such diseases in the context of a construction project in the Brazilian nation, something that was present not only in the educational army proposals, but has also permeated national debates in the medical field.

Resumen Este artículo presenta reflexiones preliminares acerca de propuestas educativas dirigidas al combate de las enfermedades venéreas en la Marina de Guerra divulgadas en Brasil en dos obras de médicos militares, en las décadas de 1920 y 1930: Enfermedades en el Mundo (1923), de autoría del médico y Capitán-de-Corveta João Pires Porto-Carrero, y Molestias Venéreas en la Marina brasileña (1933), escrito por el médico y Capitán-de-Mar-y-Guerra Artur do Valle Lins. Con ese propósito, el análisis focalizó en dos aspectos centrales: los debates nacionales sobre las enfermedades venéreas como impedimentos a la construcción de la nación brasileña, y la presencia de éstas en las propuestas educativas divulgadas en los libros producidos por médicos militares, que tematizaron el combate a las enfermedades venéreas en la Fuerza Naval del Brasil. Fue identificada una íntima relación entre eugenia, sanitarismo y la lucha contra tales enfermedades en el contexto de un proyecto de construcción de nación, algo que no solo estuvo presente en las propuestas educativas del ejército, sino que traspasó los debates nacionales del área médica.

Caracterização oncogenética da história familiar de mulheres diagnosticadas com tumores de endométrio proficientes para o sistema de reparo de pareamento incorreto de DNA / Oncogenetic characterization of the family history of women diagnosed with endometrial tumors proficient for the DNA mismatch repair system

Os tumores de endométrio fazem parte do espectro de tumores de inúmeras síndromes neoplásicas hereditárias (SNH). Entretanto, tais tumores, quando proficientes para o sistema de reparo incorreto de DNA (MMR), geralmente são classificados como cânceres esporádicos. Contudo, mesmo diante de uma provável classificação esporádica, a história familiar (HF) de portadoras dessas neoplasias pode apresentar indícios de componentes genéticos hereditários associados ao seu desenvolvimento. Para tanto, tivemos como objetivo principal, caracterizar a HF de mulheres diagnosticadas com tumores de endométrio, com estabilidade de microssatélites, proficientes para o sistema de reparo de pareamento incorreto de DNA, com a finalidade de avaliar o seu risco para síndromes neoplásicas hereditárias. Trata-se de um estudo descritivo de caráter populacional. A amostra inicial (n=58) foi acessada e caracterizada por meio da colaboração com um estudo maior, que investigou tumores de endométrio, quanto à proficiência do sistema de reparo MMR em uma casuística brasileira, a partir de dados coletados no biobanco do Serviço de Patologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. A coleta da HF teve início em abril de 2018 e foi finalizada em julho do mesmo ano. Nossa casuística final foi composta por 42 mulheres que atenderam aos critérios de inclusão/exclusão. Por meio de contato telefônico foi aplicado o Questionário de Rastreamento Primário e, posteriormente, desenhado o heredogramas das famílias, com a utilização do software PedigreeDraw. Após a coleta e o registro da HF, os heredogramas foram analisados pela pesquisadora principal deste trabalho e as famílias foram classificadas quanto ao seu risco de possuírem uma SNH. Nosso estudo possibilitou a identificação de 27 mulheres (64% da nossa casuística) que podem estar em risco para SNH. Dentre essas, no que se refere às SNH que têm o câncer colorretal no seu espectro de tumores, 26% preencheram critérios de Bethesda e 15% preencheram critérios de Amsterdam, sendo que 4% preencheram critérios para FAP atenuada. Já 11% preencheram critérios para síndrome de Câncer de Mama e Ovário Hereditários e 22% preencheram critérios para síndrome Li-Fraumeni Like tipo 1. Ressaltamos que 33% apresentaram história pessoal de câncer abaixo dos 50 anos. Os resultados aqui apresentados reforçam a importância da HF e precisam encorajar os profissionais de saúde a realizar com maior frequência a coleta e o registro da HF, ainda que seja autorreferida. Mesmo diante das novas tecnologias genômicas e do crescente conhecimento dos aspectos genéticos e de testes, a HF continua a destacar informações de risco, extremamente significativas, que vão além da suscetibilidade genética. Portanto, os indivíduos e suas famílias devem ser acompanhados com base na história pessoal e familiar para identificação de suspeitas de SNH

Endometrial tumors are part of the spectrum of tumors of innumerable hereditary neoplastic syndromes (SNH). However, such tumors, when proficient for the DNA mismatch repair (MMR), are usually classified as sporadic cancers. However, even though they are characterized as sporadic, the family history (HF) of carriers of these neoplasms may present evidence of hereditary genetic components associated with its onset and development. In order to study such evidences, we aimed to characterize the HF of women diagnosed with endometrial tumors and microsatellite stability, proficient for the DNA mismatch repair system, in order to evaluate their risk for hereditary neoplastic syndromes. This is a descriptive population-based study. The initial sample (n = 58) was reached and characterized by collaboration with a larger study, which investigated endometrial tumors, regarding the proficiency of the MMR system in a Brazilian sample. We collected data in the Pathology Center of the Hospital das Clínicas of the Medical School of Ribeirão Preto of the University of São Paulo. The HF collection began in April 2018 and was completed in July of the same year. Our final sample consisted of 42 women who met the inclusion / exclusion criteria. By telephone, the Primary Tracking Questionnaire was applied and, afterwards, the families' pedigrees were drawn using the PedigreeDraw software. After HF collection and registration, the pedigrees were analyzed by the main researcher of this study and the families were classified according to their risk of having an NHS. Our study allowed the identification of 27 women (64% of our sample) who may be at risk for SNH. For samples who have colorectal cancer in their tumor spectrum and suspicion for NHS, 26% met Bethesda criteria and 15% met Amsterdam criteria, and 4% met criteria for attenuated FAP. 11% of our sample met criteria for Hereditary Breast and Ovarian Cancer syndrome and 22% met criteria for Li-Fraumeni Like type 1 syndrome. We pointed out that 33% had a personal history of cancer under 50 years. The results presented here support the importance of HF and the need to encourage health professionals to perform HF collection and registration more frequently, even if it is self-referenced. Even in the face of new genomic technologies and growing knowledge of genetic and testing aspects, HF continues to highlight extremely significant risk information beyond genetic susceptibility. Therefore, not only the individuals but also their families should be monitored on the basis of personal and family history to identify suspected SNH

Autism spectrum disorders: an updated guide for genetic counseling / Transtornos do espectro autista: um guia atualizado para aconselhamento genético

ABSTRACT Autism spectrum disorder is a complex and genetically heterogeneous disorder, which has hampered the identification of the etiological factors in each patient and, consequently, the genetic counseling for families at risk. However, in the last decades, the remarkable advances in the knowledge of genetic aspects of autism based on genetic and molecular research, as well as the development of new molecular diagnostic tools, have substantially changed this scenario. Nowadays, it is estimated that using the currently available molecular tests, a potential underlying genetic cause can be identified in nearly 25% of cases. Combined with clinical assessment, prenatal history evaluation and investigation of other physiological aspects, an etiological explanation for the disease can be found for approximately 30 to 40% of patients. Therefore, in view of the current knowledge about the genetic architecture of autism spectrum disorder, which has contributed for a more precise genetic counseling, and of the potential benefits that an etiological investigation can bring to patients and families, molecular genetic investigation has become increasingly important. Here, we discuss the current view of the genetic architecture of autism spectrum disorder, and list the main associated genetic alterations, the available molecular tests and the key aspects for the genetic counseling of these families.

RESUMO O transtorno do espectro autista é um distúrbio complexo e geneticamente heterogêneo, o que sempre dificultou a identificação de sua etiologia em cada paciente em particular e, por consequência, o aconselhamento genético das famílias. Porém, nas últimas décadas, o acúmulo crescente de conhecimento oriundo das pesquisas sobre os aspectos genéticos e moleculares desta doença, assim como o desenvolvimento de novas ferramentas de diagnóstico molecular, tem mudado este cenário de forma substancial. Atualmente, estima-se que, por meio de testes moleculares, é possível detectar uma alteração genética potencialmente causal em cerca de 25% dos casos. Considerando-se também a avaliação clínica, a história pré-natal e a investigação de outros aspectos fisiológicos, pode-se atribuir uma etiologia para aproximadamente 30 a 40% dos pacientes. Assim, em vista do conhecimento atual sobre a arquitetura genética do transtorno do espectro autista, que tem tornado o aconselhamento genético cada vez mais preciso, e dos potenciais benefícios que a investigação etiológica pode trazer aos pacientes e familiares, tornam-se cada vez mais importantes os testes genéticos moleculares. Apresentamos aqui uma breve discussão sobre a visão atual da arquitetura genética dos transtornos do espectro autista, listando as principais alterações genéticas associadas, os testes moleculares disponíveis e os principais aspectos a se considerar para o aconselhamento genético destas famílias.

Parâmetros genéticos e efeitos de sexo e cruzamento recíproco sobre características de interesse econômico em aves F2 / Genetic parameters and effects of sex and reciprocal cross on economic traits in F2 broilers

Este estudo teve por objetivo estimar os parâmetros genéticos de características de interesse econômico, mensuradas em populações F2 desenvolvidas pela Embrapa Suínos e Aves utilizando cruzamento recíproco entre linhagens de corte e de postura. Ainda, foram avaliados os efeitos de sexo e de cruzamento recíproco sobre as características em estudo. Os pesos com um, 35 e 42 dias de idade; ganho de peso; consumo de ração e conversão alimentar entre 35 e 41 dias de idade; pesos dos pulmões, fígado, coração, moela, peito, pernas, carcaça, dorso, asas, cabeça, pés e gordura abdominal, além do comprimento do intestino, foram os fenótipos estudados. Foram estimados os componentes de variâncias genética aditiva e residual, além dos coeficientes de herdabilidade e das correlações genética e fenotípica. Os machos apresentaram maior peso para todas as características estudadas, nos dois cruzamentos recíprocos, exceto para gordura abdominal na população oriunda do cruzamento de machos de postura com fêmeas de corte. Os animais oriundos do cruzamento de machos de postura com fêmeas de corte foram mais pesados que os recíprocos, para todas as idades, além de apresentarem maior comprimento de intestino e maiores pesos de moela, carcaça, dorso, peito e cabeça. Os coeficientes de herdabilidade foram altos para consumo de ração e para os pesos ao nascimento, da moela e da gordura abdominal. As correlações fenotípicas estimadas foram, em sua maioria, baixas ou moderadas, contudo muitas correlações genéticas altas foram observadas. Ressalta-se que houve expressiva diferença nos coeficientes de herdabilidade de algumas características em função do cruzamento recíproco estudado, o que pode ser devido a efeitos materno, citoplasmático, ligados ao sexo ou imprinting.(AU)

This study aimed to estimate genetic parameters for several economic traits in F2 populations developed by Embrapa Swine and Poultry National Research Center, through reciprocal crosses of broilers and layer lines. Furthermore, sex and reciprocal cross effects were evaluated. Weights at 1, 35 and 42 days of age; weight gain, feed intake and feed conversion between 35 and 41 days of age; weights of the lungs, heart, liver, gizzard, breast, thighs, carcass, back, wings, head, legs and abdominal fat; and intestine length were studied. Residual and genetic additive variance components, heritability coefficients, and genetic and phenotypic correlations were estimated. Males were heavier than females for all studied traits in both reciprocal crosses, except for abdominal fat weight in chickens from the male layer x female broiler cross. Chickens from male layer x female broiler cross were heavier than those from its reciprocal cross, also having larger intestine length and gizzard, carcass, back, breast and head weights. The heritability coefficients were high for feed intake and body weight at birth, gizzard, and abdominal fat. The estimated phenotypic correlations were mostly lower or moderate, however, most high genetic correlations were observed. We found significant differences in heritability coefficients for some traits due to the reciprocal cross, which may be due maternal, cytoplasmic, sex-linked or imprinting effects.(AU)

Unexpected Inheritance of a Balanced Homologous translocation t(22q;22q) from father to a phenotypically normal daughter.

Rearrangements between homologous chromosomes are extremely rare and manifest mainly as monosomic or trisomic offsprings. There are remarkably few reports of balanced homologous chromosomal translocation t (22q; 22q) and only two cases of transmission of this balanced homohologous rearrangement from mother to normal daughter are reported. Robersonian translocation carriers in non‑homologous chromosomes have the ability to have an unaffected child. However, it is not possible to have an unaffected child in cases with Robersonian translocations in homologous chromosomes. Carriers of homologous chromosome 22 translocations with maternal uniparental disomy do not have any impact on their phenotype. We are presenting a family with a history of multiple first trimester miscarriages and an unexpected inheritance of balanced homologous translocation of chromosome 22 with paternal uniparental disomy. There are no data available regarding the impact of paternal UPD 22 on the phenotype. We claim this to be the first report explaining that paternal UPD 22 does not impact the phenotype.

Population based family history analysis of Brahmins in a small town in India for the prevalence of type-2 diabetes mellitus.

OBJECTIVES: The objective of this study is to determine the inheritance pattern of type‑2 diabetes and make stratification for the general population risk. MATERIALS AND METHODS: A questionnaire was developed for o btaining the family history. Analysis of the data was carried out by using student and Chi‑square tests and for stratification; the guidelines of Scheuner et al. were followed. RESULTS: The pattern of inheritance is the male sex specific (χ² =13.44). The mean age of onset of diabetes in parents was 58.61 ± 2.94 and in offspring 46.75 ± 2.54. In all 47.22 ± 11.53% families were found in high risk and 31.94 ± 10.77% in the moderate risk category. In female diabetics, the onset was in the age range of 41‑60 years. CONCLUSION: We found a high‑risk of diabetes and familial clustering in successive generations of Brahmins with prominent male sex specificity. In females onset of diabetes was coinciding with the period around menopause.

Diagnóstico de um grupo de familiares em risco para o câncer de mama: contribuição para a assistência de enfermagem / A family group on risk of breast cancer diagnosis: contribution for nursing assistance

Devido a sua alta incidência, mortalidade e custos elevados, o câncer de mama feminino é considerado um problema de saúde pública no Brasil. Sua etiologia envolve uma interação de diversos fatores denominados de risco os quais podem ser ambientais e genéticos. A história familiar positiva para câncer de mama é um importante fator de risco para o desenvolvimento dessa patologia. Conhecer esses fatores e as medidas de proteção permite que mulheres com risco elevado possam criar estratégias pessoais que venham minimizar os danos causados pela doença. Diante do exposto, o presente estudo tem como objetivos avaliar o nível de conhecimento de mulheres acerca do risco de desenvolverem câncer de mama em decorrência do vínculo familiar com a população portadora desta neoplasia matriculada no Hospital do Câncer III, unidade do Instituto Nacional de Câncer (INCA) especializada no tratamento e controle do câncer de mama, localizada no município do Rio de Janeiro, Brasil; descrever as características sociodemográficas das mulheres familiares de pacientes portadoras de câncer de mama e descrever a história reprodutiva e hormonal, bem como seus hábitos de cuidado com a saúde. Metodologia: trata-se de um estudo exploratório sob a perspectiva quantitativa, transversal e descritiva com 52 mulheres que acompanhavam suas familiares internadas em unidade clínica e cirúrgica do Hospital do Câncer III. A coleta de dados ocorreu no período entre julho e agosto de 2011. A técnica de amostragem adotada foi a não probabilística, intencional Para o cálculo amostral aplicou-se a fórmula de população infinita. Foram selecionadas as seguintes variáveis para compor o estudo: aspectos sociodemográficos, aspectos da vida reprodutiva e hormonal, aspectos de cuidados com a saúde e aspectos de esclarecimento relacionados à patologia/doença. Realizou-se entrevista estruturada com utilização de um formulário composto por 63 questões...

Due to the incidence, mortality and high costs, female breast cancer is considered a Health Care issue in Brazil. Its etiology binds an interaction of various risk factors which can be environmental and genetic ones. A positive family history for breast cancer is an important risk factor for the development of this pathology. Knowing the factors and protection measures allow the women with high risk create personal strategies that minimize the damage caused by the disease. Objectives: evaluate the level of knowledge of the women regarding the risk of breast cancer development related to family history with population which carries this neoplasia assisted by the Hospital do Câncer III, Cancer National Institute (INCA) branch specialized on breast cancer treatment and control, located at the city of Rio de Janeiro, Brazil; describe the social demographical characters of the women whose relatives are breast cancer patients and report their hormonal and reproductive history as well as their health care habits. Methodology: It consists of an exploratory study under a quantitative perspective in a descriptive and transversal way with 52 women that accompanied their hospitalized relatives in a clinic and surgery unity of Hospital do Câncer III. The data collection was performed between July and August 2011. The sampling technique adopted was intentionally the non-probabilistic. The applied sample size calculation was infinite population. The selected variables to compose the study were the following: social demographical aspects, reproductive and hormonal life aspects, health care aspects and awareness concerning the pathology/disease. The structured interview counted with a form of 63 questions...

Inheritance patterns, consanguinity & risk for asthma.

Background & objectives: Family history is an important risk factor for the development of asthma, contingent upon genetic and environment interaction. Since there is paucity of data on asthma inheritance in Indian population, the present study was undertaken to investigate the inheritance patterns of asthma and the effect of family history and consanguineous marriage on asthma inheritance. Methods: A total of 200 families, 100 index children and 100 index adults with clinically diagnosed asthma, along with 400 non-asthmatic children and adults as controls were selected for the present study. Information about the family history of each patients and controls was collected and analyzed pedigrees were also constructed. Results: A history of asthma in any member of the family was observed in 44.5 per cent of cases and 5.3 per cent of controls (P < 0.001). A differential risk of developing asthma was noted in family history of asthma in different first and second degree relatives of children and adult patients. Consanguineous marriage was also noted in parents in 24.5 per cent of cases and 12.3 per cent of controls (P< 0.001). The most common mode of asthma inheritance was recessive. Interpretation & conclusions: Our results showed that consanguineous marriage and family history of asthma are important determinants in the development of asthma in the offspring.

Morphological and microsatellite diversity associated with ecological factors in natural populations of Medicago laciniata Mill. (Fabaceae).

Genetic variability in 10 natural Tunisian populations of Medicago laciniata were analysed using 19 quantitative traits and 12 polymorphic microsatellite loci. A large degree of genetic variability within-populations and among-populations was detected for both quantitative characters and molecular markers. High genetic differentiation among populations for quantitative traits was seen, with Q(ST) = 0.47, and F(ST) = 0.47 for microsatellite markers. Several quantitative traits displayed no statistical difference in the levels of Q(ST) and F(ST). Further, significant correlations between quantitative traits and eco-geographical factors suggest that divergence in the traits among populations may track environmental differences. There was no significant correlation between genetic variability at quantitative traits and microsatellite markers within populations. The site-of-origin of eco-geographical factors explain between 18.13% and 23.40% of genetic variance among populations at quantitative traits and microsatellite markers, respectively. The environmental factors that most influence variation in measured traits among populations are assimilated phosphorus (P(2)0(5)) and mean annual rainfall, followed by climate and soil texture, altitude and organic matter. Significant associations between eco-geographical factors and gene diversity, He, were established in five microsatellite loci suggesting that these simple sequence repeats (SSRs) are not necessarily biologically neutral.

A search for transmission ratio distortions in offspring from crosses between inbred mice.

Equal transmission of the two alleles at a locus from a heterozygote parent to the offspring is rarely violated. Beside the differential embryonic mortality, nondisjunction and gene conversion that are rather irregular forms of transmission-ratio distortion (TRD), there are two major forms of departure from Mendelian segregation. The first, found in females, based on the asymmetric nature of female meiosis, is usually referred to as meiotic drive, and has been well documented in a few cases. The second is segregation distortion found in males. There are several known male-related segregation distortion systems that are caused by different fertilizing capacity of sperm cells carrying alternative alleles at a particular locus. Observation of TRD effects requires a sufficient number of offspring produced by a parental pair. As individuals in a population most likely have different genotypes in TRD affecting loci, the total transmission ratio is close to the expected Mendelian ratio and masks potential TRD effects. Highly inbred strains of laboratory mice provide a very good model for studying this phenomenon, because comparing two mice strains is effectively similar as comparison of two individuals in a population. This study tests both forms of TRD in progeny of F1 hybrids from reciprocal crosses of inbred mice. Three previously unknown instances of TRD in females were observed. Therefore, this study concludes that some genes in females may carry alleles that can cause segregation distortion.

Effect of obesity on rat reproduction and on the development of their adult offspring

The aim of the present study was to assess the reproductive parameters of obese Wistar rats and to determine the frequency of their obese adult offspring. Neonatal rats were divided into two groups: F1 generation, induced to obesity by monosodium glutamate (MSG; F1MSG, N = 30), and rats given saline (F1CON, N = 13). At 90 days of age all animals were mated, producing the F2 offspring (F2CON, N = 28; F2MSG, N = 15). Reproductive parameters (fertility, pregnancy, and delivery indexes) were evaluated in F1 rats. F2 newborns were weighed, and the obesity parameter for F1 and F2 generations was determined from months 5 to 7 of life. At month 7, periovarian fat was weighed and no differences were found. Mean newborn weight also did not differ. The F1 and F2MSG groups presented approximately 90 percent of obese rats since month 5 of life, whereas F1 and F2CON groups presented only 33 percent. There was no difference in periovarian weight among groups. Although obesity did not affect reproductive parameters, obese dams (F1MSG) were responsible for the appearance of obesity in the subsequent generation. Thus, obesity induced by neonatal MSG administration did not interfere with reproduction, but did provide a viable model for obesity in second-generation adult Wistar rats. This model might contribute to a better understanding of the pathophysiological mechanisms involved in transgenerational obesity.

A Brazilian family with Brown-Vialetto-van Laere syndrome with autosomal recessive inheritance

We report the first Brazilian family with Brown-Vialetto-van Laere syndrome. The presence of consanguineous marriages and illness affecting three sisters and one niece support an autosomal recessive transmission. The age at onset of the illness ranged from 12 to 20 years old. The time interval between hearing loss and involvement of other cranial nerves varied from 3 to 12 years. MRI demonstrated bulbar atrophy and also high intensity signal at T2 weighted and fluid attenuated inversion recovery (FLAIR) sequences.

Descrevemos a primeira família brasileira com síndrome de Brown-Vialetto-van Laere. Os pacientes são três irmãs e uma sobrinha provenientes de casamentos consangüíneos, o que fortalece a hipótese de transmissão autossômica recessiva. A idade de aparecimento dos sintomas variou entre 12 e 20 anos. A latência entre a perda auditiva e o envolvimento de outros nervos cranianos variou de 3 a 12 anos. O estudo de imagem por ressonância magnética demonstrou atrofia bulbar além de alteração de sinal nas seqüências ponderadas em T2 e FLAIR (fluid attenuated inversion recovery).

Da herança à localização cerebral: sobre o determinismo biológico de condutas indesejadas / From heritage to cerebral localization: on the biological determinism of undesired conducts

Analisamos os argumentos utilizados, em dois momentos diferentes do século XX, para justificar o recurso a explicações biológicas de condutas consideradas como socialmente indesejadas. Referimo-nos, inicialmente, aos estudos realizados pelos higienistas de início do século, cujas explicações estavam centradas no caráter orgânico e inato dos desvios, para continuar logo com os recentes estudos da neurociência que se propõem a localizar as condutas nas sinapses inadequadas e nas explicações referidas a deficiências químicas do cérebro.

The article analyzes the arguments used in two distinct moments of the 20th century, to justify the use of biological explanations for conducts considered as socially undesirable. Firstly we refer to studies of hygienists in the early century, whose explanation were centered on the organic and innate character of deviations, then we analyze the recent studies in the neurosciences which try to locate these conducts in inadequate synapses and in explanations related to chemical cerebral deficiencies.

New evidence for nucleolar dominance in hybrids of Drosophila arizonae and Drosophila mulleri

Drosophila mulleri (MU) and D. arizonae (AR) are cryptic species of the mulleri complex, mulleri subgroup, repleta group. Earlier cytogenetic studies revealed that these species have different regulatory mechanisms of nucleolar organizing activity. In these species, nucleolar organizing regions are found in both the X chromosome and the microchromosome. In the salivary glands of hybrids between MU females and AR males, there is an interspecific dominance of the regulatory system of the D. arizonae nucleolar organizer involving, in males, amplification and activation of the nucleolar organizer from the microchromosome. The authors who reported these findings obtained hybrids only in that cross-direction. More recently, hybrids in the opposite direction, i.e., between MU males and AR females, have been obtained. The purpose of the present study was to evaluate, in these hybrids, the association of the nucleoli with the chromosomes inherited from parental species in order to cytogenetically confirm the dominance patterns previously described. Our results support the proposed dominance of the AR nucleolar organizer activity over that of MU, regardless of cross-direction.

The prima donna of epigenetics: the regulation of gene expression by DNA methylation

This review focuses on the mechanisms of DNA methylation, DNA methylation pattern formation and their involvement in gene regulation. Association of DNA methylation with imprinting, embryonic development and human diseases is discussed. Furthermore, besides considering changes in DNA methylation as mechanisms of disease, the role of epigenetics in general and DNA methylation in particular in transgenerational carcinogenesis, in memory formation and behavior establishment are brought about as mechanisms based on the cellular memory of gene expression patterns.

Peripheral genotype-phenotype correlations in Asian Indians with type 2 diabetes mellitus.

OBJECTIVE: A genome-wide scan of gene expression in leucocytes in Asian Indians with type 2 diabetes was performed and correlated with their known phenotype. METHODS: Microarray gene profiling of 13,474 sequence-verified, non-redundant human cDNAs was done to study leukocyte gene expression in Asian Indians with type 2 diabetes (DM: n=3) and matched controls (n=3). RESULTS: Significant differential expression (fold change <0.3 or >3) was noted for 897 genes in DM vs. controls. The 147 known genes in this category belonged to following broad functional groups (%): enzyme (32), nucleic acid binding (22), ligand binding or carrier (10), signal transducer (9), transporter (7), structural protein (6), cell adhesion (3), tumor suppressor (3), transcription factor binding (2), enzyme inhibitor (2), chaperone (2), cell cycle regulator (1), and defense/immunity protein (1). The 20 genes with at least a 3-fold change, annotated with known phenotypic associations in the current gene databank (phenotype association, fold change) were aspartoacylase (Canavan disease, 9.96), growth hormone receptor (Laron dwarfism, idiopathic short stature, 8.25), lipoprotein lipase (familial chylomicronemia syndrome, lipoprotein lipase deficiency, 8.00), vitamin D (1,25- dihydroxyvitamin D3) receptor (involutional osteoporosis, vitamin D resistant rickets, 7.94), intercellular adhesion molecule 1 human rhinovirus receptor (cerebral malaria susceptibility, 7.16), peroxisomal membrane protein 3 35-kDa (Refsum disease, infantile form, Zellweger syndrome-3, 6.00), Bardet-Biedl syndrome 2 (Bardet-Biedl syndrome, 5.87), ribosomal protein S19 (Diamond Blackfan anemia, 5.85), apolipoprotein C-III (hypertriglyceridemia, 5.44), argininosuccinate lyase (argininosuccinicaciduria, 5.22), myosin VA (Griscelli syndrome-type pigmentary dilution with mental retardation, 4.92), lysozyme (renal amyloidosis, 4.17), SAM domain, SH3 domain and nuclear localisation signals 1 (Cherubism, 4.12 ), von Hippel-Lindau syndrome (hemangioblastoma, cerebellar, somatic, von Hippel-Lindau syndrome, 3.94), early-onset breast cancer 1 (BRCA1, papillary serous carcinoma of the peritoneum, 3.73), UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (inclusion body myopathy, autosomal recessive, sialuria, 3.53), apolipoprotein A-I (amyloidosis, 3 or more types, hypoalphalipoproteinemia, 3.29), midline 1 Opitz/BBB syndrome (Opitz G syndrome, type I, 3.28), ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide (familial hemiplegic migraine, 3.05). Canavan disease, Zellweger syndrome, infantile Refsum disease, Griscelli syndrome, cherubism, breast cancer, peritoneal papillary serous carcinoma, Opitz G/BBB syndrome, and familial hemiplegic migraine (FHM) are phenotypes not previously reported in association with type 2 DM, but whose underlying genes were up-regulated in this peripheral genome scan of Asian Indians. CONCLUSION: Rare and/or previously unknown phenotypes linked to known genes with significant differential expression in type 2 DM are reported. Further testing of heterogeneity in diabetes phenotype syndromes may reveal common pathogenic mechanisms and potential candidate genes responsible for type 2 DM.

Inheritance of parthenocarpy in summer squash (Cucurbita pepo L)

The inheritance of the tendency to set parthenocarpic fruit in the summer squash (Cucurbita pepo L.) line Whitaker was studied. Two parental lines, Whitaker (parthenocarpic) and Caserta (non-parthenocarpic), and the F1 and F2 generations and backcrosses to both parents were tested. The parthenocarpic tendency of individual plants was scored on a scale from 1 (non-parthenocarpic fruit) to 5 (parthenocarpic fruit). The Whitaker line produced parthenocarpic fruit and had a mean score of 4.2, whereas Caserta did not set parthenocarpic fruit and had a score of 1.55. The heritability estimates indicated that genetic gains from selection were feasible. The additive-dominant model showed a good fit, with epistasis being negligible or nonexistent. The hypothesis of monogenic inheritance with incomplete dominance was not rejected within the degree of dominance range from 0.2 to 0.5. These results indicate that parthenocarpy is controlled by a single locus, with incomplete dominance in the direction of parthenocarpic expression