Uniparental genetic systems: a male and a female perspective in the domestic cattle origin and evolution

Over the last 20 years, the two uniparentally inherited marker systems, namely mitochondrial DNA and Y chromosome have been widely employed to solve questions about origin and prehistorical range expansions, demographic processes, both in humans and domestic animals. The mtDNA and the Y chromosome, with their unique patterns of inheritance, continue to be extremely important source of information. These markers played significant roles in farm animals in the evaluation of the genetic variation within- and among-breed strains and lines and have widely applied in the fields of linkage mapping, paternity tests, prediction of breeding values in genome-assisted selection, analysis of genetic diversity within breeds detection of population admixture, assessment of inbreeding and relationships between breeds, and assignment of individuals to their breed of origin. This approach offers a unique opportunity to save genetic resources and achieving improved productivity. In the past years, significant progress was achieved in reconstructing detailed cattle phylogenies; many studies indicated multiple parental sources and several levels of phylogeographic structuring. More detailed researches are still in progress in order to provide a more comprehensive picture of such extant variability. This paper is focused on reviewing the use of the two uniparental markers as valuable tool for the characterization of cattle genetic diversity. Furthermore, their implications in animal breeding, management and genetic resources conservation are also reported.

Temporal distribution of tuberculosis in the State of Amazonas, Brazil

Tuberculosis (TB) is one of the infectious diseases that contributes most to the morbidity and mortality of millions of people worldwide. Brazil is one of 22 countries that accounts for 80% of the tuberculosis global burden. The highest incidence rates in Brazil occur in the States of Amazonas and Rio de Janeiro. The aim of this study was to describe the temporal distribution of TB in the State of Amazonas. Between 2001 and 2011, 28,198 cases of tuberculosis were reported in Amazonas, distributed among 62 municipalities, with the capital Manaus reporting the highest (68.7%) concentration of cases. Tuberculosis was more prevalent among males (59.3%) aged 15 to 34 years old (45.5%), whose race/color was predominantly pardo (64.7%) and who had pulmonary TB (84.3%). During this period, 81 cases of multidrug-resistant TB were registered, of which the highest concentration was reported from 2008 onward (p = 0.002). The municipalities with the largest numbers of indigenous individuals affected were São Gabriel da Cachoeira (93%), Itamarati (78.1%), and Santa Isabel do Rio Negro (70.1%). The future outlook for this region includes strengthening the TB control at the primary care level, by expanding diagnostic capabilities, access to treatment, research projects developed in collaboration with the Dr. Heitor Vieira Dourado Tropical Medicine Foundation .;Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD).; and financing institutions, such as the project for the expansion of the Clinical Research Center and the creation of a hospital ward for individuals with transmissible respiratory diseases, including TB.

Populations of Odontesthes (Teleostei: Atheriniformes) in the Andean region of Southern South America: body shape and hybrid individuals

The original distribution area of the Patagonian 'pejerrey' Odontesthes hatcheri has been subjected to the introduction of a related species; the Bonaerensean 'pejerrey' Odontesthes bonariensis. This species currently coexists with O. hatcheri in lakes and reservoirs, and can interbreed and produce fertile hybrid offspring. The purposes of this study were; a) the extensive sampling of Patagonian and Andean-Cuyan populations of pejerrey, b) the species identification according to taxonomic key, c) validation of taxonomic results on the basis of mitochondrial DNA composition, and d) applying morphometric analysis to explore the effects of hybridization and environmental conditions on body shape. Cytochrome b sequence analysis showed a high degree of genetic divergence between species and low intraspecific variation in O. hatcheri. Geometric Morphometric Analyses detected shape differences in agreement with diagnostic characteristics of each species. Putative hybrids exhibiting intermediate diagnostic characteristics were identified by Geometric Morphometric Analysis. Significant regressions between body shape and total phosphorus and altitude were found, suggesting a dependence on trophic web structure. This multi-level approach suggests the introgression of O. bonariensis into several O. hatcheri populations throughout Patagonia. Managers should take this into account when considering further exotic introductions into regions where non-native fishes have not yet become established.

La distribución original del 'pejerrey' patagónico Odontesthes hatcheri ha sido sometida en las últimas décadas a la introducción de una especie relacionada; el 'pejerrey' Bonaerense Odontesthes bonariensis. Ambas especies coexisten actualmente en algunos lagos y embalses debido a prácticas de siembra y pueden cruzarse y producir progenie híbrida y fértil. Los propósitos de este estudio fueron a) un amplio muestreo de las poblaciones patagónicas y andino-cuyanas del pejerrey, b) la identificación de las especies de acuerdo con la clave taxonómica, c) la validación de los resultados taxonómicos sobre la base de la composición del ADN mitocondrial y d) aplicar el análisis morfométrico para explorar los efectos de la hibridización y las condiciones ambientales sobre la forma corporal. El análisis de la secuencia del Citocromo b mostró un alto grado de divergencia genética entre ambas especies y una muy baja variación intraespecífica en O. hatcheri. El análisis de la Morfometría Geométrica detectó diferencias de forma coincidentes con las características diagnósticas de cada especie. Presuntos híbridos exhibiendo características diagnósticas intermedias fueron identificados por el análisis de la Morfometría Geométrica. Regresiones significativas entre la forma corporal y la concentración total de fósforo y la altitud fueron halladas, sugiriendo una dependencia con la estructura de la trama trófica. Este enfoque múltiple sugiere la introgresión de genes de O. bonariensis dentro de varias poblaciones de O. hatcheri a lo largo de la Patagonia. Las autoridades de aplicación deberían tomar en cuenta estos riesgos al momento de considerar nuevas introducciones de especies exóticas en regiones donde estas especies no se encuentren previamente establecidas.

Efeitos do consumo agudo e crônico de etanol sobre as funções mitocondriais: estudos em ratos Wistar (Rattus novergicus) / Effects of short and long-term ethanol consumption on mitochondrial functions: studies in Wistar rats (Rattus novergicus)

O número de indivíduos que sofrem com patologias associadas ao consumo abusivo de etanol tem aumentado significativamente no último século. Como consequência desse fato, os custos associados ao tratamento do alcoolismo, bem como das doenças associadas a ele também têm aumentado, onerando o sistema de saúde e se tornando um problema de saúde pública de grande relevância atualmente. Os mecanismos moleculares que desencadeiam muitas dessas doenças não estão completamente esclarecidos. O tecido hepático é o mais afetado pelo etanol e as mitocôndrias têm sido apontadas como alvos cruciais na toxicidade hepática induzida pelo álcool. Logo, o objetivo desse trabalho foi investigar como o consumo de etanol afeta o estado redox e o metabolismo mitocondriais no fígado. Ratos Wistar machos adultos jovens e de meia-idade receberam ad libitum solução alcoólica 25% (v/v) como única fonte de líquido. Os grupos controle receberam somente água. Ambos os grupos receberam ração ad libitum. Mitocôndrias hepáticas foram isoladas usando técnicas padrão. O consumo de ração e de líquidos foi significativamente menor em animais que ingeriram álcool, resultando em menor ganho de massa corpórea nos protocolos utilizados. As mitocôndrias dos animais que consumiram etanol apresentaram menores níveis de respiração em condição basal e quando energizadas com substratos respiratórios. A atividade e os níveis protéicos de citocromo c oxidase foi menor nos grupos tratados com etanol. Independente da duração do período de tratamento, mitocôndrias hepáticas de animais que ingeriram álcool foram menos susceptíveis à transição de permeabilidade mitocondrial induzida por cálcio, quando comparadas às mitocôndrias dos animais do grupo controle...

The number of people suffering from alcoholism has increased significantly over the last century. As a result, costs associated with treating the addiction itself as well as the associated pathologies have also increased, such that this is considered as public health issue. Furthermore, the molecular events leading to several of these diseases are not yet clearly understood. Hepatic tissue is the most affected by alcohol, and mitochondria have been suggested to be a crucial target in alcohol-induced liver toxicity. Thus, the aim of our study was to investigate how ethanol consumption affects the redox state and mitochondrial metabolism in the liver. Young adult and middle-aged male Wistar rats were given a 25 % (v/v) ethanol solution as the only source of drinking water. Control groups received water only. Liver mitochondria were isolated using standard techniques. Food and water intake was significantly lower in alcohol-drinking rats, resulting in lower weight gain during the treatment regimes. Mitochondria from the alcohol-drinking group had lower respiration under levels in basal condition, when energized by substrates feeding electrons into complexes I and IV. Cytochrome c oxidase activity and protein levels were lower in the alcohol group as well. Additionally, regardless of the length of the treatment, liver mitochondria from the alcohol-treated animals were more resistant to Ca2+-induced mitochondrial permeability transition (MPT), when compared to mitochondria from control animals. This effect was abrogated by oxidizing agents of pyridine nucleotides (acetoacetate, diamide or tert butylhydroperoxide) or in uncoupled mitochondria. We also found that liver mitochondria from the alcohol-drinking rats had a more reduced pyridine nucleotide pool and higher NAD(P)H/NAD(P)+ ratios. In addition, Nampt (an enzyme of the NAD+ synthetic pathway) protein levels did not differ after alcohol consumption. ..

eNOS se correlaciona com a biogênese mitocondrial em corações com cardiopatia congênita e cianose / eNOS correlates with mitochondrial biogenesis in hearts of congenital heart disease with cyanosis

FUNDAMENTO: O programa de biogênese mitocondrial no coração parece apresentar remodelação adaptativa após estresse biomecânico e oxidativo. Os mecanismos adaptativos que protegem o metabolismo do miocárdio durante a hipóxia são coordenados, em parte, pelo óxido nítrico (NO). OBJETIVO: Observar a biogênese mitocondrial e expressão do óxido nítrico sintase (NOS) em corações de cardiopatia congênita com cianose; discutir a resposta mitocondrial à hipóxia crônica do miocárdio. MÉTODOS: Foram investigados 20 pacientes com defeitos cardíacos cianóticos (n = 10) ou acianóticos (n = 10). Foram estudadas amostras do miocárdio na via de saída ventricular direita, tomadas durante a operação. A análise morfométrica de mitocôndrias foi realizada por microscopia eletrônica de transmissão. A relação mtDNA/nDNA foi determinada com PCR em tempo real. Os níveis de transcrição da subunidade I da citocromo c oxidase (COXI), coativador-1α do receptor γ ativado por proliferador de peroxissoma (PGC-1α), o fator respiratório nuclear 1 (NRF1), e fator de transcrição mitocondrial A (Tfam) foram detectados por reação em cadeia da polimerase via transcriptase reversa (RT-PCR) ativado por fluorescência em tempo real. Os níveis proteicos de COXI e nNOS, iNOS e eNOS foram medidos por técnica de Western Blot. RESULTADOS: A densidade volumétrica mitocondrial (Vv) e a densidade numérica (Nv) foram significativamente elevadas em pacientes com cianose, em comparação com a cardiopatia congênita acianótica. MtDNA elevada e suprarregulação dos níveis de COXI, PGC-1 α, NRF1 e Tfam mRNA foram observadas em pacientes cianóticos. Os níveis de proteína de COXI e eNOS foram significativamente maiores no miocárdio de pacientes cianóticos que nos de acianóticos. Os níveis de transcrição do PGC-1α se correlacionam com os níveis de eNOS. CONCLUSÃO: A biogênese mitocondrial é ativada no miocárdio da via de saída ventricular na cardiopatia congênita com cianose, que ...

BACKGROUND: Mitochondrial biogenesis program in heart appears to exhibit adaptive remodeling following biomechanical and oxidative stress. The adaptive mechanisms that protect myocardium metabolism during hypoxia are coordinated in part by nitric oxide (NO). OBJECTIVE: To observe mitochondrial biogenesis and nitric oxide synthase (NOS) expression in hearts of congenital heart disease with cyanosis, discuss mitochondrial response to chronic hypoxia in myocardium. METHODS: 20 patients with cyanotic (n=10) or acyanotic cardiac defects (n=10) were investigated. Samples from the right ventricular outflow tract myocardium taken during operation were studied. Morphometric analysis of mitochondria was performed with transmission electron microscope. Relative mtDNA/nDNA ratio was determined with real-time PCR. Cytochrome c oxidase subunit I (COXI), peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (Tfam) transcript levels were detected by real-time fluorescent RT-PCR. COXI and nNOS, iNOS and eNOS protein levels were measured with western blot. RESULTS: Mitochondrial volume density (Vv) and numerical density (Nv) were significantly elevated in patients with cyanotic compared to acyanotic congenital heart disease. Elevated mtDNA and up-regulated COXI, PGC-1α, NRF1 and Tfam mRNA levels were observed in cyanotic patients. Protein levels of COXI and eNOS were significantly higher in the myocardium of cyanotic than of acyanotic patients. PGC-1α transcript levels correlated with the levels of eNOS. Conclusion: Mitochondrial biogenesis is activated in right ventricular outflow tract myocardium in congenital heart disease with cyanosis, which could be the adaptive response to chronic hypoxia and possibly involves eNOS up-regulation. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

Aplication of authenticity criteria in mitochondrial studies on archaic bone remains from a prehispanic Muisca population / Aplicación de criterios de autenticidad en estudios mitocondriales en restos óseos de un grupo poblacional muisca prehispánico

Introduction: Ancient DNA (aDNA)studies can support hypotheses regarding ancient populations; molecular studies can analyze the local population's genetic composition, minimizing biases introduced by later migrations, demographic expansions, mutations, and bottleneck effects. These analyses must be performed with special care because of the low DNA concentrations and contamination risk; therefore, it is necessary to establish protocols to guarantee the reproducibility and veracity of results. Objective: The present study aims to establish a protocol to obtain ancient DNA from 16 pre-Columbian bone samples found in an excavation performed in the area ®Candelaria La Nueva¼ in Bogota, Colombia, dated in the period ®Muisca Tardio¼. Methods: Four founder mitochondrial DNA Amerindian haplotypes were analyzed by high resolution restriction enzyme analyses, obtaining fragments between 121 and 186 base pairs (bp). Different analyses were performed following a strict control of authenticity criteria regarding laboratory conditions, including: positive and negative controls, reproducibility of results, and verification of particular characteristics present in ancient DNA. Results: Results obtained from the bone samples showed the exclusive presence of haplogroup A in the population studied. This data support the statement of the archaeologists of a single biological population in space and time. The distribution of this haplogroup in a 100% frequency supports the hypothesis of Chibcha genetic affiliation. Conclusion: The present study is a contribution to the study of genetic diversity in archaic American populations, allowing the integration of geographic and historic data with genetic characterization techniques associated with linguistic, ethnographic, and glottochronology patterns. Following the protocol proposed in the present study allows fulfilling authenticity criteria for ancient samples with the available techniques.

Introducción: Los estudios de ADN arcaico (aADN) pueden verificar hipótesis sobre las poblaciones del pasado, permiten analizar la composición genética, pudiéndose así soslayar sesgos introducidos por migraciones, expansiones demográficas, mutaciones y cuellos de botella acontecidos con posterioridad. Los métodos de análisis son objeto de cuidadoso procedimiento debido a la dificultad de recuperación y a la posibilidad de contaminación, por lo tanto es necesario establecer protocolos que garanticen la reproducibilidad y veracidad de los resultados. Objetivo: El presente estudio tiene como fin establecer un protocolo para la obtención de ADN arcaico en 16 muestras óseas precolombinas encontradas en una excavación del sector de Candelaria La Nueva, Bogotá, Colombia, fechadas dentro del período Muisca Tardío. Métodos: Se estudiaron 4 haplogrupos fundadores amerindios presentes en el ADN mitocondrial arcaico, mediante enzimas de restricción con base en estudios de alta resolución obteniendo fragmentos de tamaños entre 121 y 186 pares de bases (pb). Los distintos análisis se realizaron observando un estricto control de los criterios de autenticidad en relación con las condiciones de laboratorio, incluyendo el uso de controles y blancos, la reproducibilidad de resultados y la verificación de las características particulares que presenta el ADN arcaico. Resultados: Los resultados obtenidos de las muestras óseas arcaicas establecieron la presencia única del haplogrupo ®A¼ en la población estudiada. Estos datos apoyan la afirmación de los arqueólogos en cuanto a que se trata de una misma población biológica tanto espacial como temporalmente. La distribución de este haplogrupo en una frecuencia del 100% soporta la filiación genética con los grupos chibcha.

Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10 / Pseudo-obstrução intestinal em paciente com diabetes mitocondrial que apresentou boa resposta ao tratamento adjunto com coenzima Q10

Maternally inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. This subtype of diabetes is characterized by maternal transmission, young age at onset and bilateral hearing impairment. Besides diabetes and deafness, the main diagnostic features, a wide range of multisystemic symptoms may be associated with the A3243G mutation. Organs that are most metabolically active, such as muscles, myocardium, retina, cochlea, kidney and brain are frequently affected. Gastrointestinal tract symptoms are also common in patients with mitochondrial disease and constipation and diarrhea are the most frequent manifestations. However, there are few prior reports of intestinal pseudo obstruction in MIDD patients. Here we report the case of a patient with MIDD associated with the mtDNA A3243G mutation who developed chronic intestinal pseudo obstruction, and the introduction of Coenzyme Q10 as adjunctive therapy led to a solution of the pseudo obstruction.

Diabetes mitocondrial ou diabetes e surdez de herança maternal (MIDD, acrônimo de maternally inherited diabetes and deafness) é freqüentemente associado à mutação mitocondrial A3243G. Esse subtipo de diabetes é caracterizado por transmissão materna, disacusia neuro-sensorial bilateral e idade precoce de aparecimento. Além do diabetes e da surdez, principais características diagnósticas, outros sintomas em diferentes órgãos podem também associar-se à mutação A3243G. Os órgãos que são metabolicamente mais ativos, tais como músculos, miocárdio, retina, cóclea, rim e cérebro, são freqüentemente afetados. Sintomas do trato gastrintestinal também são comuns em pacientes com doença mitocondrial, sendo diarréia e obstipação as manifestações mais freqüentes. Entretanto, há poucos relatos de pseudo-obstrução intestinal em portadores de diabetes mitocondrial. Este relato descreve o caso de uma paciente com diabetes mitocondrial que apresentou pseudo-obstrução intestinal e que com a introdução de coenzima Q10, como terapia adjunta, teve resolução o quadro.

Síndrome de Kearns-Sayre / Kearns-Sayre syndrome

A síndrome de Kearns-Sayre é uma patologia rara, que acarreta piora da qualidade de vida; caracteriza-se por oftalmoplegia externa progressiva, fraqueza muscular e distúrbios na condução cardíaca. A entidade integra um grupo de desordens do metabolismo mitocondrial, denominadas miopatias mitocondriais ou citopatias mitocondriais.

Kearns-Sayres syndrome is a rare pathology which leads to a worse quality of life of the individual; it is characterized by progressive external ophthalmoplegia, muscular weakness, and cardiac conduction defects. The disease belongs to a group of mitochondrial metabolic disorders, named mitochondrial myopathies of mitochondrial cytopathies.

Danos moleculares em pacientes urêmicos submetidos à hemodiálise / Molecular damage in uremic patients on hemodialysis

Os efeitos tóxicos decorrentes do estado urêmico e do tratamento através de hemodiálise vêmsendo sugeridos como responsáveis por danos no DNA em pacientes com insuficiência renal crônica.Dessa forma, muitos trabalhos têm desenvolvido marcadores capazes de identificar esses danosatravés da análise cromossômica, teste de micronúcleos, teste do cometa, teste eletroquímico e,mais recentemente, análise do DNA mitocondrial. Considerando que esses danos podem aumentara incidência de câncer, mais estudos devem continuar sendo desenvolvidos nesse sentido.

The toxic effects caused by the uremic state and hemodialysis have been suggested asbeing responsible for DNA damage in patients with chronic renal failure. Thus, many researchershave developed markers capable of identifying these damages using chromosome analysis,micronucleus test, comet assay, electrochemical test and, more recently, mitochondrial DNA analysis.Further studies must be undertaken, since these damages can increase the incidence of cancer.

Pode a genética definir quem deve se beneficiar das cotas universitárias e demais ações afirmativas? / Can the genetics define who must benefit of university quotas and too much affirmative action?

Neste trabalho nós usamos o instrumental da genética molecular e da genética de populações para estimar quantitativamente a contribuição africana para a formação do povo brasileiro. Examinamos dois compartimentos genômicos: o DNA mitocondrial, de herança matrilínea, e o DNA nuclear, de herança bi-parental. Os estudos mitocondriais revelaram que aproximadamente 30 por cento dos brasileiros autoclassificados como brancos e 80 por cento dos negros apresentam linhagens maternas características da áfrica subsaariana. A partir destes dados, estimamos que pelo menos 89 milhões de brasileiros são afro-descendentes, um número bem superior aos 76 milhões de pessoas que se declararam negros (pretos e pardos) no censo de 2000 do IBGE. As análises de polimorfismos nucleares com marcadores "informativos de ancestralidade" mostraram resultados mais expressivos ainda. Usando estudos de brasileiros autoclassificados como brancos de várias regiões do Brasil, estimamos que aproximadamente 146 milhões de brasileiros (86 por cento da população) apresentam mais de 10 por cento de contribuição africana em seu genoma. Estes números devem ser levados em conta nas discussões sobre ações afirmativas no Brasil, mas em um sentido descritivo e não prescritivo.