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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Transgenerational inheritance of DNA methylation alterations at the H19 imprinting control region following maternal ethanol exposure in mice

Ungerer, Michelle January 2013 (has links)
A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree in Master of Science (Medicine) in the Division of Human Genetics / Foetal Alcohol Syndrome (FAS) is characterised by growth retardation, craniofacial dysmorphology and neurodevelopmental deficits. Whilst, not all alcohol exposed offspring display alcohol-related developmental anomalies, the percentage of affected offspring is greatly underestimated. Common behavioural disorders, such as ADHD and anxiety, are likely to be linked to the transgenerational effects of in utero alcohol exposure. Epigenetics has been highlighted as a potential mechanism in the aetiology of alcohol teratogenesis due to alcohol’s disruptive effects on the folate pathway, and subsequently DNA methylation. The imprinted H19/Igf2 domain is critical in foetal growth and development. The locus is regulated by the methylation-sensitive CTCF binding protein which binds to the H19 imprinting control region (ICR) upstream of the H19 locus. CTCF binding allows for the reciprocal expression of H19 and Igf2 in an allele-specific parent of origin manner. Due to the monoallelic expression of imprinted genes, DNA methylation changes within their control regions can lead to altered gene expression and possibly disease. Furthermore, if these alterations occur in the germline, disease states or susceptibility to disease may be transmittable to future generations. A mouse model was used to investigate the potential transgenerational effects of F0 chronic maternal ethanol exposure on parturition, growth, locomotor activity and anxiety. Furthermore, the transgenerational inheritance of H19 ICR DNA methylation was investigated and its possible contribution to the aforementioned phenotypes was determined. Phenotypic analysis revealed significantly reduced F1 fertility following alcohol exposure (P = 0.003) but no other significant perturbations in parturition. Although not significant at all generations, alcohol’s effects on growth and behaviour were apparent. DNA was extracted from tail biopsies, bisulfite modified and the CTCF1 and CTCF2 regions of the H19 ICR amplified. DNA methylation quantification via Pyrosequencing revealed significantly reduced mean methylation profiles at CTCF1 and CTCF2 within the F1 EtOH exposed group (P = 0.021), with CpG sites 1, 2, 4 and 6 of CTCF1 and CpG sites 1, 2, 3 (P = 0.021) and 5 (P = 0.043) of CTCF2 displaying statistically significant differences. In contrast, the EtOH group of the F2 generation showed an increase in CTCF1 mean methylation that trended towards significance (P = 0.083) suggesting a potential recovery or compensatory mechanism within the epigenetic machinery. The F3 generation EtOH exposed group displayed decreased CTCF1 mean methylation levels (P = 0.083). The F2 and F3 generations showed no significant difference in CTCF2 methylation levels between treatment groups. The significant change in CTCF1 methylation at the F1 generation and the trend towards significance in the F2 and F3 generations indicated potential transgenerational inheritance of altered H19 ICR DNA methylation. Correlations between DNA methylation at the H19 CTCF1 and CTCF2 binding sites with growth rate and behaviour measures revealed no significant relationships. This dissertation supports the involvement of epigenetic mechanisms in alcohol teratogenesis. In addition it contributes to the growing field of transgenerational epigenetic inheritance, with implications for the treatment of those with Foetal Alcohol Syndrome and/or Foetal Alcohol Spectrum Disorders and their progeny.
2

Contribuição para a caracterização clínica das ataxias hereditárias autossômicas recessivas / Contribution to clinical characterization of autosomal recessive hereditary ataxias

Leão, Emilia Katiane Embiruçu de Araujo 16 September 2009 (has links)
As ataxias hereditárias autossômicas recessivas compõem um grupo de doenças heterogêneas, que necessitam de criteriosa avaliação clínica, de exames complementares e, algumas vezes, de testes genéticos para o diagnóstico. A partir da revisão da literatura, foi elaborado um algoritmo para auxiliar a investigação diagnóstica deste grupo. Esta tese tem como objetivo apresentar os resultados da investigação de três formas de ataxias recessivas: 1. Síndrome de Joubert, caracterizada por hipotonia precoce, atraso do desenvolvimento neuropsicomotor, ataxia e padrão respiratório irregular no período neonatal ou anormalidades na motricidade ocular extrínseca. Apresenta amplo espectro clínico, assim como heterogeneidade genética. Alterações renal, hepática e da retina são freqüentes. A presença de hipoplasia do vermis cerebelar, alongamento dos pedúnculos cerebelares superiores e aumento da fossa interpeduncular, aos cortes axiais da ressonância magnética (RM) do encéfalo, constituem o sinal do dente molar, considerado critério radiológico obrigatório para o diagnóstico. Aqui é apresentada uma série de cinco pacientes que preenchem critérios clínicos e radiológico de síndrome de Joubert e tem grande variabilidade fenotípica: duas crianças têm a forma pura (subtipo 1), uma tem associadamente retinopatia (subtipo 3), uma tem amaurose congênita de Leber e alteração renal (subtipo 4) e a outra apresenta associadamente coloboma corioretiniano e alterações hepáticas (subtipo 5); 2. Ataxia com Deficiência de Vitamina E, que apresenta fenótipo semelhante ao da ataxia de Friedreich, progressão mais lenta, baixo nível sérico de -tocoferol e é tratável com reposição da vitamina E. Frequente no sul da Itália e norte da África, sem relatos no Brasil. Foram investigados quatro pacientes pertencentes a duas famílias: três apresentavam o quadro clínico típico acompanhado de distonia em mãos, manifestação pouco relatada, mas que pode contribuir para a diferenciação clínica com ataxia de Friedreich. O outro paciente foi identificado em fase pré-sintomática, após o diagnóstico ser estabelecido em dois irmãos, e permanece com sinais sutis de alteração do equilíbrio após de 5 anos de reposição de vitamina E. Nos demais, a reposição de vitamina E promoveu melhora dos sintomas e impediu que a doença se agravasse; 3. Xantomatose Cerebrotendínea, que está relacionada à alteração no metabolismo do colesterol, com redução na produção dos ácidos biliares e acúmulo de colestanol, um metabólito tóxico. Catarata congênita ou juvenil e diarréia crônica são manifestações precoces. Ataxia cerebelar, paraparesia espástica, declínio cognitivo e xantomas tendíneos completam o quadro clínico. Na RM do encéfalo, a presença de hipersinal nos núcleos denteados, nas sequências T2-pesada e FLAIR, é sugestiva da doença. Três pacientes, pertencentes a duas famílias, com alterações clínicas e radiológica foram investigados. Em todos, o colestanol sérico encontravase elevado. A espectrocopia por RM detectou no cerebelo pico em 1,2-1,4 ppm, sugestivo de lipídio, achado até o momento não descrito. Após início do tratamento com ácido quenodeoxicólico, observou-se melhora da marcha. / Autosomal recessive hereditary ataxias belong to a group of heterogeneous disorders, for which detailed clinical evaluation, ancillary exams, and sometimes, genetic tests, are required for diagnosis. After literature review, an algorithm was built to help the investigation of this group. The objective of this thesis is to present the results of investigation of three forms of recessive ataxias: 1. Joubert syndrome is a condition characterized by early hypotonia, developmental delay, ataxia and neonatal respiratory disturbances or abnormal eye movement. It has a wide clinical spectrum and is genetically heterogeneous. Renal, hepatic and retina abnormalities are often seen. A combination of midline cerebellar vermis hypoplasia, deepened interpenducular fossa, and thick, elongated superior cerebellar penduncles gives to the axial view of the midbrain an appearance of a molar tooth at brain magnetic ressonance image (MRI) study. Molar tooth sign is considered as obligatory radiologic criteria to diagnosis. In this study we present a series of five patients that have clinical and radiologic criteria to Joubert syndrome and a large phenotypic variability: Two children have a pure form (subgroup 1), one child has an associated retinopathy (subgroup 3), the other has Leber congenital amaurosis and kidney abnormalitties (subgroup 4), and another has chorioretinal coloboma and hepatic abnormalities (subgroup 5); 2. Ataxia with vitamin E deficiency, which has a phenotype similar to Friederich ataxia but slowest progression, is characterized by low levels of serum -tocopherol and is treatable with vitamin E. This ataxia is common in South Italy and North Africa, but was not reported in Brazil. Four patients from two different families were studied. Three of them have typical clinical features and hands dystonia, a probably underreported feature which might helps its distinction from Friedreich ataxia. The other case was identified in a presymptomatic stage, after family investigation. After five years of treatment with vitamin E, subtle balance disturbance was still present. The remaing three patientes improved with vitamin E supplementation and disease progression stopped; 3. Cerebrotendinous xantomathosis (CTX) is a disorder of cholesterol metabolism, characterized by reduction of bile acid synthesis and accumulation of cholestanol, a toxic metabolic. Congenital or juvenile cataract and chronic diarrhea are early manifestations. Cerebellar ataxia, spastic paraplegia, cognitive impairment and tendinous xanthomas are also seen. Brain MRI T2-weighted and FLAIR sequences disclosed dentate nucleus hypersignal, a quite feature in CTX. Three patients from two different families, with clinical and radiologic features were studied. In all, serum cholestanol was elevated. MRI spectroscopy demonstrated in cerebellum a peak in 1,2-1,4 ppm, which is an possibly a lipid, not previously described. Treatment with chenodeoxycholic acid improved their gait.
3

An analysis of gender ratios in families with one or more individuals affected by systemic lupus erythematosus

McBride, Whitney Lee. January 2010 (has links) (PDF)
Thesis--University of Oklahoma. / Bibliography: leaves 36-40.
4

Contribuição para a caracterização clínica das ataxias hereditárias autossômicas recessivas / Contribution to clinical characterization of autosomal recessive hereditary ataxias

Emilia Katiane Embiruçu de Araujo Leão 16 September 2009 (has links)
As ataxias hereditárias autossômicas recessivas compõem um grupo de doenças heterogêneas, que necessitam de criteriosa avaliação clínica, de exames complementares e, algumas vezes, de testes genéticos para o diagnóstico. A partir da revisão da literatura, foi elaborado um algoritmo para auxiliar a investigação diagnóstica deste grupo. Esta tese tem como objetivo apresentar os resultados da investigação de três formas de ataxias recessivas: 1. Síndrome de Joubert, caracterizada por hipotonia precoce, atraso do desenvolvimento neuropsicomotor, ataxia e padrão respiratório irregular no período neonatal ou anormalidades na motricidade ocular extrínseca. Apresenta amplo espectro clínico, assim como heterogeneidade genética. Alterações renal, hepática e da retina são freqüentes. A presença de hipoplasia do vermis cerebelar, alongamento dos pedúnculos cerebelares superiores e aumento da fossa interpeduncular, aos cortes axiais da ressonância magnética (RM) do encéfalo, constituem o sinal do dente molar, considerado critério radiológico obrigatório para o diagnóstico. Aqui é apresentada uma série de cinco pacientes que preenchem critérios clínicos e radiológico de síndrome de Joubert e tem grande variabilidade fenotípica: duas crianças têm a forma pura (subtipo 1), uma tem associadamente retinopatia (subtipo 3), uma tem amaurose congênita de Leber e alteração renal (subtipo 4) e a outra apresenta associadamente coloboma corioretiniano e alterações hepáticas (subtipo 5); 2. Ataxia com Deficiência de Vitamina E, que apresenta fenótipo semelhante ao da ataxia de Friedreich, progressão mais lenta, baixo nível sérico de -tocoferol e é tratável com reposição da vitamina E. Frequente no sul da Itália e norte da África, sem relatos no Brasil. Foram investigados quatro pacientes pertencentes a duas famílias: três apresentavam o quadro clínico típico acompanhado de distonia em mãos, manifestação pouco relatada, mas que pode contribuir para a diferenciação clínica com ataxia de Friedreich. O outro paciente foi identificado em fase pré-sintomática, após o diagnóstico ser estabelecido em dois irmãos, e permanece com sinais sutis de alteração do equilíbrio após de 5 anos de reposição de vitamina E. Nos demais, a reposição de vitamina E promoveu melhora dos sintomas e impediu que a doença se agravasse; 3. Xantomatose Cerebrotendínea, que está relacionada à alteração no metabolismo do colesterol, com redução na produção dos ácidos biliares e acúmulo de colestanol, um metabólito tóxico. Catarata congênita ou juvenil e diarréia crônica são manifestações precoces. Ataxia cerebelar, paraparesia espástica, declínio cognitivo e xantomas tendíneos completam o quadro clínico. Na RM do encéfalo, a presença de hipersinal nos núcleos denteados, nas sequências T2-pesada e FLAIR, é sugestiva da doença. Três pacientes, pertencentes a duas famílias, com alterações clínicas e radiológica foram investigados. Em todos, o colestanol sérico encontravase elevado. A espectrocopia por RM detectou no cerebelo pico em 1,2-1,4 ppm, sugestivo de lipídio, achado até o momento não descrito. Após início do tratamento com ácido quenodeoxicólico, observou-se melhora da marcha. / Autosomal recessive hereditary ataxias belong to a group of heterogeneous disorders, for which detailed clinical evaluation, ancillary exams, and sometimes, genetic tests, are required for diagnosis. After literature review, an algorithm was built to help the investigation of this group. The objective of this thesis is to present the results of investigation of three forms of recessive ataxias: 1. Joubert syndrome is a condition characterized by early hypotonia, developmental delay, ataxia and neonatal respiratory disturbances or abnormal eye movement. It has a wide clinical spectrum and is genetically heterogeneous. Renal, hepatic and retina abnormalities are often seen. A combination of midline cerebellar vermis hypoplasia, deepened interpenducular fossa, and thick, elongated superior cerebellar penduncles gives to the axial view of the midbrain an appearance of a molar tooth at brain magnetic ressonance image (MRI) study. Molar tooth sign is considered as obligatory radiologic criteria to diagnosis. In this study we present a series of five patients that have clinical and radiologic criteria to Joubert syndrome and a large phenotypic variability: Two children have a pure form (subgroup 1), one child has an associated retinopathy (subgroup 3), the other has Leber congenital amaurosis and kidney abnormalitties (subgroup 4), and another has chorioretinal coloboma and hepatic abnormalities (subgroup 5); 2. Ataxia with vitamin E deficiency, which has a phenotype similar to Friederich ataxia but slowest progression, is characterized by low levels of serum -tocopherol and is treatable with vitamin E. This ataxia is common in South Italy and North Africa, but was not reported in Brazil. Four patients from two different families were studied. Three of them have typical clinical features and hands dystonia, a probably underreported feature which might helps its distinction from Friedreich ataxia. The other case was identified in a presymptomatic stage, after family investigation. After five years of treatment with vitamin E, subtle balance disturbance was still present. The remaing three patientes improved with vitamin E supplementation and disease progression stopped; 3. Cerebrotendinous xantomathosis (CTX) is a disorder of cholesterol metabolism, characterized by reduction of bile acid synthesis and accumulation of cholestanol, a toxic metabolic. Congenital or juvenile cataract and chronic diarrhea are early manifestations. Cerebellar ataxia, spastic paraplegia, cognitive impairment and tendinous xanthomas are also seen. Brain MRI T2-weighted and FLAIR sequences disclosed dentate nucleus hypersignal, a quite feature in CTX. Three patients from two different families, with clinical and radiologic features were studied. In all, serum cholestanol was elevated. MRI spectroscopy demonstrated in cerebellum a peak in 1,2-1,4 ppm, which is an possibly a lipid, not previously described. Treatment with chenodeoxycholic acid improved their gait.
5

Herdabilidade das funções cognitivas em um estudo de coorte familiar: Projeto Corações de Baependi / Heritability of cognitive functions in a family-based cohort study: The Baependi Heart Project

Taporoski, Tâmara Pessanha 20 March 2018 (has links)
INTRODUÇÃO: Muitos são os fatores que contribuem para o desempenho cognitivo, porém o peso dos fatores genético, ambiental e sociodemográfico na composição das funções cognitivas ainda é pouco conhecido, especialmente em amostras brasileiras. Portanto, como o cálculo de herdabilidade estima a proporção da variância total do fenótipo atribuída ao fator genético, o presente trabalho avaliou a herdabilidade do desempenho em diferentes testes cognitivos em uma coorte de famílias com o propósito de melhor investigar os aspectos biológicos associados à performance cognitiva. MÉTODOS: Foram avaliados 1 717 indivíduos (60% mulheres, idades entre 18 e 91 anos e, 0 a 23 anos de escolarização), todos participantes do \'Projeto Corações de Baependi\'. Os domínios cognitivos foram avaliados por meio dos testes de lista de palavras (usando três escores diferentes), fluência verbal semântica - categoria animais (escores total e particionados por quartis de minuto) - e o teste de trilhas - parte B. As estimativas de herdabilidade, bem como o impacto de covariáveis sobre o desempenho nos testes, foram calculadas utilizando-se o modelo misto poligênico implementado no software SOLAR. RESULTADOS: Os valores de herdabilidade e respectivas covariáveis de influência significativa para os fenótipos (melhor modelo ajustado) foram os seguintes: teste de lista de palavras - escore total (h2= 0,30; idade, sexo e escolaridade), teste de lista de palavras - primeira evocação (h2= 0,22; idade, escolaridade, cronotipo e horário do dia) -, teste de fluência verbal (h2= 0,21; sexo, idade, escolaridade e horário do dia) - apresentando 4 quartis de minuto, o primeiro quartil (h2= 0,17; idade, escolaridade e horário do dia), o segundo quartil (h2= 0,09; escolaridade e horário do dia), o terceiro quartil (h2= 0,12; escolaridade e horário do dia) e o quarto quartil (h2= 0,0003; escolaridade e sexo) -, teste de lista de palavras - evocação tardia (h2= 0,28; idade e escolaridade) e teste de trilhas (h2= 0,42; sexo, idade e escolaridade). CONCLUSÕES: Os resultados indicaram que o teste de trilhas apresentou o componente genético mais alto de todos os testes e foi mais fortemente influenciado por idade. Testes de lista de palavras estimaram herdabilidades intermediárias e o teste de fluência verbal indicou a menor variância genética dentre os fenótipos e foi expressivamente impactado por escolaridade. O primeiro quartil de minuto do teste de fluência verbal apresentou maior componente herdável sugerindo que processos cognitivos automáticos são melhor explicados por componentes genéticos do que os demais. Efeitos de idade e escolaridade indicaram exercer influência significativa sobre todos os fenótipos e, por consequência, sobre o desempenho cognitivo de uma maneira geral. Maiores graus de escolaridade indicaram melhores performances e o avanço da idade indicou declínio no desempenho cognitivo. As estimativas do componente genético das funções cognitivas podem ser exploradas em estudos de associação genômica ampla / INTRODUCTION: Many factors contribute to cognitive performance. The specific contribution of genetic, environmental or sociodemographic factors in the composition of cognitive functions is still unclear, especially in Brazilian samples. The calculation of heritability estimates the proportion of the total variance of the phenotype which is attributed to its genetic component. Thus, in order to better investigate the biological aspects associated to cognitive performance, this work assessed the heritability of performance in different cognitive tests in a family-based cohort. METHODS: 1,717 participants in the Baependi Heart Study were evaluated (60% women, ages between 18 and 91 years-old, 0 to 23 years of schooling). Cognitive domains were assessed using the words list test (immediate and delayed recall), semantic verbal fluency - category animals (total score and partitioned in quartiles of minute) and the trail making test - part B. The heritability estimates, as well as the impact of covariates over the performance, were calculate using the SOLAR software. RESULTS: The heritability values and the respective covariates of significant influence to the phenotypes (best-fit model) were as follows: Words list test (h2= 0,30; age and schooling), words list test - firs trial recall (h2= 0,22; age, schooling, chronotype and time of day), verbal fluency test (h2= 0,21; sex, age, schooling and time of day), quartiles of minute of the verbal fluency test - first quartile (h2= 0,17; age, schooling and time of day), second quartile (h2= 0,09; schooling and time of day), third quartile (h2= 0,12; schooling and time of day), fourth quartile (h2= 0,0003; schooling and sex), words list test - delayed recall (h2= 0,28; age and schooling and, trail making test (h2= 0,42; sex, age and, schooling). The results indicated that the trail making test - part B presented the highest genetic component of all tests and that it was strongly influenced by age. Words list tests showed intermediate heritability, and the verbal fluency test reflected the lowest heritability amongst the phenotypes, being markedly influenced by schooling. The first quartile of minute of the verbal fluency test presented the highest heritable component, suggesting that automatic cognitive processes are better explained by genetic component then the following ones. Effects of age and schooling influenced significantly all phenotypes and, as a consequence, cognitive performance as a whole. Higher education level was associated with better performances and advanced age with a decrease in cognitive performance. Our findings of genetic components for cognitive functions can be exploited in genome-wide association studies
6

Effect of DNA methyltransferase 1 on transmission ratio distortion and epigenetic inheritance

Yang, Lanjian, 1976- January 2008 (has links)
Epigenetic modification of DNA plays an important role in gene regulation. During gametogenesis and early embryogenesis epigenetic states are reset to ensure embryonic-specific gene expression patterns after fertilization. However, certain genomic regions may resist epigenetic reprogramming. This may result in transgenerational epigenetic inheritance. Earlier, a grandparental origin dependent (GPO) transmission ratio distortion (TRD) of alleles in the distal region of mouse chromosome 12 had been found (Croteau et al ., 2002). The distorted region overlaps with the imprinted region of chromosome 12. The mechanism underlying this TRD is unknown, and we hypothesized that it was due to failure to reset imprints in the imprinted region in a proportion of germ cells. Such an imprint resetting failure would represent a particular case of transgenerational epigenetic inheritance. DNA (Cytosine-5) methyltransferase 1 (DNMT1) plays a key role in the maintenance of epigenetic states in mammalian genomes. To test the role of DNA methylation and DNMT1 in the genesis of TRD and its relationship to epigenetic inheritance we investigated the effect of Dnmt1 loss-of-function mutations using two mouse models: GPO (grandparental origin dependent)-TRD (transmission ratio distortion) and epigenetic inheritance at the agouti locus. Here, we report that Dnmt1 mutations have a modifying parental effect on the transmission of grandparental chromosome 12 alleles. However, the same Dnmt1 mutation did not affect the agouti coat color inheritance patterns in mice that inherited the Avy (agouti viable yellow) mutant allele from the father. Our results suggest that Dnmt1 is a trans-acting modifier of allelic transmission and support the role of epigenetic states in the genesis of TRD.
7

Herdabilidade das funções cognitivas em um estudo de coorte familiar: Projeto Corações de Baependi / Heritability of cognitive functions in a family-based cohort study: The Baependi Heart Project

Tâmara Pessanha Taporoski 20 March 2018 (has links)
INTRODUÇÃO: Muitos são os fatores que contribuem para o desempenho cognitivo, porém o peso dos fatores genético, ambiental e sociodemográfico na composição das funções cognitivas ainda é pouco conhecido, especialmente em amostras brasileiras. Portanto, como o cálculo de herdabilidade estima a proporção da variância total do fenótipo atribuída ao fator genético, o presente trabalho avaliou a herdabilidade do desempenho em diferentes testes cognitivos em uma coorte de famílias com o propósito de melhor investigar os aspectos biológicos associados à performance cognitiva. MÉTODOS: Foram avaliados 1 717 indivíduos (60% mulheres, idades entre 18 e 91 anos e, 0 a 23 anos de escolarização), todos participantes do \'Projeto Corações de Baependi\'. Os domínios cognitivos foram avaliados por meio dos testes de lista de palavras (usando três escores diferentes), fluência verbal semântica - categoria animais (escores total e particionados por quartis de minuto) - e o teste de trilhas - parte B. As estimativas de herdabilidade, bem como o impacto de covariáveis sobre o desempenho nos testes, foram calculadas utilizando-se o modelo misto poligênico implementado no software SOLAR. RESULTADOS: Os valores de herdabilidade e respectivas covariáveis de influência significativa para os fenótipos (melhor modelo ajustado) foram os seguintes: teste de lista de palavras - escore total (h2= 0,30; idade, sexo e escolaridade), teste de lista de palavras - primeira evocação (h2= 0,22; idade, escolaridade, cronotipo e horário do dia) -, teste de fluência verbal (h2= 0,21; sexo, idade, escolaridade e horário do dia) - apresentando 4 quartis de minuto, o primeiro quartil (h2= 0,17; idade, escolaridade e horário do dia), o segundo quartil (h2= 0,09; escolaridade e horário do dia), o terceiro quartil (h2= 0,12; escolaridade e horário do dia) e o quarto quartil (h2= 0,0003; escolaridade e sexo) -, teste de lista de palavras - evocação tardia (h2= 0,28; idade e escolaridade) e teste de trilhas (h2= 0,42; sexo, idade e escolaridade). CONCLUSÕES: Os resultados indicaram que o teste de trilhas apresentou o componente genético mais alto de todos os testes e foi mais fortemente influenciado por idade. Testes de lista de palavras estimaram herdabilidades intermediárias e o teste de fluência verbal indicou a menor variância genética dentre os fenótipos e foi expressivamente impactado por escolaridade. O primeiro quartil de minuto do teste de fluência verbal apresentou maior componente herdável sugerindo que processos cognitivos automáticos são melhor explicados por componentes genéticos do que os demais. Efeitos de idade e escolaridade indicaram exercer influência significativa sobre todos os fenótipos e, por consequência, sobre o desempenho cognitivo de uma maneira geral. Maiores graus de escolaridade indicaram melhores performances e o avanço da idade indicou declínio no desempenho cognitivo. As estimativas do componente genético das funções cognitivas podem ser exploradas em estudos de associação genômica ampla / INTRODUCTION: Many factors contribute to cognitive performance. The specific contribution of genetic, environmental or sociodemographic factors in the composition of cognitive functions is still unclear, especially in Brazilian samples. The calculation of heritability estimates the proportion of the total variance of the phenotype which is attributed to its genetic component. Thus, in order to better investigate the biological aspects associated to cognitive performance, this work assessed the heritability of performance in different cognitive tests in a family-based cohort. METHODS: 1,717 participants in the Baependi Heart Study were evaluated (60% women, ages between 18 and 91 years-old, 0 to 23 years of schooling). Cognitive domains were assessed using the words list test (immediate and delayed recall), semantic verbal fluency - category animals (total score and partitioned in quartiles of minute) and the trail making test - part B. The heritability estimates, as well as the impact of covariates over the performance, were calculate using the SOLAR software. RESULTS: The heritability values and the respective covariates of significant influence to the phenotypes (best-fit model) were as follows: Words list test (h2= 0,30; age and schooling), words list test - firs trial recall (h2= 0,22; age, schooling, chronotype and time of day), verbal fluency test (h2= 0,21; sex, age, schooling and time of day), quartiles of minute of the verbal fluency test - first quartile (h2= 0,17; age, schooling and time of day), second quartile (h2= 0,09; schooling and time of day), third quartile (h2= 0,12; schooling and time of day), fourth quartile (h2= 0,0003; schooling and sex), words list test - delayed recall (h2= 0,28; age and schooling and, trail making test (h2= 0,42; sex, age and, schooling). The results indicated that the trail making test - part B presented the highest genetic component of all tests and that it was strongly influenced by age. Words list tests showed intermediate heritability, and the verbal fluency test reflected the lowest heritability amongst the phenotypes, being markedly influenced by schooling. The first quartile of minute of the verbal fluency test presented the highest heritable component, suggesting that automatic cognitive processes are better explained by genetic component then the following ones. Effects of age and schooling influenced significantly all phenotypes and, as a consequence, cognitive performance as a whole. Higher education level was associated with better performances and advanced age with a decrease in cognitive performance. Our findings of genetic components for cognitive functions can be exploited in genome-wide association studies
8

Ultraviolet-B Radiation : Effects on Pollen of 34 Taxa, and Inheritance Patterns and Carryover of Radiation Response in Arabidopsis

Torabinejad, Javad 01 May 1999 (has links)
Although considerable research has addressed effects of elevated ultraviolet-B (UV-8) radiation on vegetative plant structures and processes, the reproductive biology and patterns of inheritance of UV-B tolerance have received much less attention. I examined the effects of UV-B radiation on pollen of 34 taxa. I also addressed questions concerning the patterns of inheritance of UV-B tolerance in Arabidopsis thaliana and examined potential cumulative carryover effects of UV-B exposure through multiple generations of this species. In the first study, a significant reduction in pollen germination occurred in only five species, but pollen tube growth in more than half of the species exhibited significant reductions . Proportionate to their numbers in this survey of 34 taxa: Monocotyledonous species were more sensitive to UV-8 than the dicotyledonous species, wild species were more sensitive than cultivated species, and pollen from plants growing in the field was somewhat more sensitive than pollen from plants grown in the greenhouse. The results also suggested a possible adaptation to UV-8 radiation during the course of the season. The second study probed patterns of inheritance of UV-8 tolerance. General combining ability and specific combining ability were both significant for several traits in Arabidopsis. This suggests that plant breeders may develop UV-8 tolerant strains of plant species both in the form of pure lines and hybrids. In the third experiment, I found that a significant carryover effect of UV-B exposure through multiple generations Arabidopsis thaliana was evident in a subsequent generation, in either the presence or absence of UV-B, once differences in the reactions of different ecotypes were taken into account. However, instead of an expected accumulation of UV-B effect as a greater number of generations were exposed to the radiation, there was an apparent reversion of the cumulative, carryover effect. This was evident in that plants exposed to seven generations of UV-B exhibited much less carryover effect than did plants exposed for only three generations.
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Effect of DNA methyltransferase 1 on transmission ratio distortion and epigenetic inheritance

Yang, Lanjian, 1976- January 2008 (has links)
No description available.
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Paternal Effects on Metabolism in Mammals: A Dissertation

Shea, Jeremy M. 19 March 2015 (has links)
The following work demonstrates that paternal diet controls medically important metabolic phenotypes in offspring. We observe transmission of dietary information to the zygote via sperm, and this information evades reprogramming that typically occurs after fertilization. Cytosine methylation is implicated as a major contributor to meiotic epigenetic inheritance in several transgenerational phenomena. Our extensive characterization of the sperm methylome reveals that diet does not significantly affect methylation patterns. However, we find that extensive epivariability in the sperm epigenome makes important contributions to offspring variation. Importantly, coordinate cytosine methylation and copy number changes over the ribosomal DNA locus contributes to variation in offspring metabolism. Thus, rDNA variability acts independently of postadolescent paternal diet to influence offspring metabolism. Therefore, at least two mechanisms exist for epigenetically controlling offspring metabolism: stochastic epivariation and diet acting by an unknown mechanism to further modulate metabolism. This work argues that an offspring's phenotype can no longer be viewed solely as the result of genetic interactions with the developmental environment - the additional influences of paternal environment and inherited epigenetic variability must also be considered. These findings reveal novel contributions to metabolism that could revolutionize how we think about the risk factors for human health and disease.

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