Дисертації з теми "Parental origin effects"

Les études d'association pan-génomiques (GWAS) ont révolutionné ces 15 dernières années la recherche en génétique humaine en permettant l'identification de milliers de variants génétiques associés à des maladies complexes comme les maladies cardiovasculaires et des traits biologiques comme des facteurs de la coagulation. Toutefois, ces études reposent principalement sur des modèles additifs qui ne permettent pas de capturer toute la complexité des mécanismes génétiques qui peuvent être mis en jeu. Les interactions entre gènes (épistasie), entre gènes et facteurs environnementaux ainsi que les effets épigénétiques dû à l’empreinte parentale, sont ainsi négligés. L'objectif principal de cette thèse est de détecter des effets génétiques non additifs dans des études d'association pan-génomiques sur les taux plasmatiques de 2 facteurs importants de la cascade de la coagulation : le facteur V et le facteur de Willebrand. Pour cela, une méthodologie statistique peu connue et reposant sur une modification du test de Brown-Forsythe a été utilisée dans plusieurs cohortes du consortium CHARGE. Cette méthodologie a permis d’identifier le locus PSKH2 comme nouvel acteur participant à la régulation des taux plasmatiques de Facteur V. L’application de cette stratégie de recherche aux taux plasmatiques de Facteur de Willebrand a mis en évidence les limites de la méthode en présence de plusieurs polymorphismes en déséquilibre de liaison et influençant le phénotype étudié. À l'avenir, il serait intéressant de poursuivre ces recherches en explorant d'autres facteurs de la coagulation et en utilisant d’autres méthodologies statistiques moins sujettes à l’influence du déséquilibre de liaison. Les études d’association pan-génomiques (GWAS) ont révolutionné ces 15 dernières années la recherche en génétique humaine en permettant l’identification de milliers de variants génétiques associés à des maladies complexes comme les maladies cardiovasculaires et des traits biologiques comme des facteurs de la coagulation. Toutefois, ces études reposent principalement sur des hypothèses d’effets génétiques additifs qui ne permettent pas de capturer toute la complexité des mécanismes génétiques qui peuvent être mis en jeu. Les interactions entre gènes (épistasie), entre gènes et facteurs environnementaux ainsi que les effets épigénétiques dus par exemple à l’empreinte parentale, sont ainsi négligés. L’objectif principal de cette thèse est de détecter des effets génétiques non additifs influençant les taux plasmatiques de 2 facteurs importants de la cascade de la coagulation : le Facteur V et le Facteur de von Willebrand, et ce à partir de données génétiques pan-génomiques. Pour cela, une méthodologie statistique peu connue et reposant sur une modification du test de Brown-Forsythe a été utilisée dans plusieurs cohortes du consortium CHARGE. Cette méthodologie a permis d’identifier le locus PSKH2 comme nouvel acteur participant à la régulation des taux plasmatiques de Facteur V. L’application de cette stratégie de recherche aux taux plasmatiques de Facteur de von Willebrand a mis en évidence les limites de la méthode en présence de plusieurs polymorphismes en déséquilibre de liaison et influençant le phénotype étudié. À l’avenir, il serait intéressant de poursuivre ces recherches en explorant d’autres facteurs de la coagulation et en utilisant d’autres méthodologies statistiques moins sujettes à l’influence du déséquilibre de liaison
Genome-wide association studies (GWAS) have revolutionized human genetics research over the past 15 years by enabling the identification of thousands of genetic variants associated with complex diseases, such as cardiovascular diseases, and biological traits, such as coagulation factors. However, these studies primarily rely on additive models, which do not capture the full complexity of genetic mechanisms that may be involved. Interactions between genes (epistasis), gene-environment interactions, and epigenetic effects such as those due to parental imprinting are thus neglected. The main objective of this thesis is to detect, from GWAS data, non-additive genetic effects on plasma levels of two important factors in the coagulation cascade: Factor V and von Willebrand Factor. To achieve this, a neglected statistical methodology based on a modification of the Brown-Forsythe test was applied in several cohorts from the CHARGE consortium. This methodology identified the PSKH2 locus as a novel player in the regulation of plasma Factor V levels. Applying this research strategy to von Willebrand Factor plasma levels highlighted the limitations of the method in the presence of multiple polymorphisms in linkage disequilibrium that influence the studied phenotype. In the future, it would be interesting to pursue this research by exploring other coagulation factors and using other statistical methodologies less subject to the influence of linkage disequilibrium

Objective: To investigate the association of previously reported single nucleotide polymorphisms (SNPs) in relation to orofacial clefts and assess their interaction with environmental factors. Methods: Genome-wide SNP genotypes were obtained for case-parent triads from the EUROCRAN and ITALCLEFT studies. Candidate SNPs were selected from a previous genome-wide association study (Shi et al., 2012) along with surrounding SNPS for a total of 2142 genotyped and imputed SNPs. A total of 411 case-parent triads and 25 case-parent dyads were analyzed using log-linear models to test for maternal and parent-of-origin effects along with their interaction with maternal smoking and maternal folic acid consumption. Results: A significant association (q = 0.025) was detected for a region in the ATXN3 gene. This significance refers to the interaction between maternal periconceptional smoking and maternal genetic effects. Nominally significant associations in genes relating to the brain were also detected. Conclusion: SNPs in the ATXN3 region warrant further investigation.

Background:In angiosperms, the endosperm plays a crucial placenta-like role in that not only is it necessary for nurturing the embryo, but also regulating embryogenesis through complicated genetic and epigenetic interactions with other seed compartments and is the primary tissue in which genomic imprinting occurs.Results:We observed a gradual increase of paternal siRNA expression in the early stages of kernels and an expected 2:1 maternal to paternal ratio in 7-DAP endosperm via sequencing of small interfering RNA (siRNA) transcriptomes in developing kernels (0, 3 and 5 days after pollination (DAP)) and endosperms (7, 10 and 15 DAP) from the maize B73 and Mo17 reciprocal crosses. Additionally, 460 imprinted siRNA loci were identified in the endosperm, with the majority (456/460, 99.1%) being maternally expressed at 10 DAP. Moreover, 13 out of 29 imprinted genes harbored imprinted siRNA loci within their 2-kb flanking regions, a significant higher frequency than expected based on simulation analysis. Additionally, gene ontology terms of "response to auxin stimulus", "response to brassinosteroid stimulus" and "regulation of gene expression" were enriched with genes harboring 10-DAP specific siRNAs, whereas those of "nutrient reservoir activity", "protein localization to vacuole" and "secondary metabolite biosynthetic process" were enriched with genes harboring 15-DAP specific siRNAs.Conclusions:A subset of siRNAs subjected to imprinted expression pattern in maize developing endosperm, and they are likely correlated with certain imprinted gene expression. Additionally, siRNAs might influence nutrient uptake and allocation processes during maize endosperm development.

The purpose of this study was to examine the effects of family of origin experiences and religiosity on parenting styles among low income black parents. Traditional research methods were explored. Non-probability sampling was utilized to collect data from forty respondents who were all parents of children attending a head start program. Self-reports of own parenting styles, family of origin parenting styles, and level of religiosity were used to measure study variables. Results indicated that family of origin experiences effect one's current parenting styles. Respondents who reported family of origin experiences of authoritarian parenting styles were also found to be authoritarian in their own styles; the same was true for the second category of permissive/authoritative parenting styles. Results for religiosity indicated that one's level of religiosity, either low or high, did not significantly effect one's current parenting style.

Recent advances in plant genetic engineering offer substantial benefits to farmers throughout the world. Genetic research has identified many exogenous genes that could considerably decrease production costs through transgene-mediated resistance to insect, viral, fungal and bacterial pathogens. Potato can be produced from true potato seed (TPS) through a sexual polyploidization step, known as 4x-2x hybridization. Little is known regarding the stability of transgenes through sexual polyploidization in potato, although studies have associated ploidy elevation with transgene silencing in plants such as Arabidopsis thaliana. In the present study, potato was transformed with two different transgenes, cry3Aa and PVYo cp, and transgene expression was analyzed through 4x-2x hybridization. Transgene introgression did not affect fertility or agronomic performance (tuber set, average tuber weight, total tuber yield) of the resulting 4x-2x hybrids; however, reduced seed germination was observed for several transgenic lines in an in vitro study. Ploidy elevation did not affect a highly expressed single copy cry3Aa transgene, simplex or duplex, transmitted through pollen to 4x-2x hybrids. By contrast, multiple copies of cry3Aa triggered significant transgene silencing in diploids and silencing was further pronounced upon pollen transmission to 4x-2x hybrids. Crosses between two, single insert plants demonstrated additional evidence that multiple cry3Aa transgenes resulted in reduced expression, as well as provided evidence for maternal effects on expression of the cry3Aa transgene. Finally, Cry3Aa expression levels of progeny derived from low expressing, multiple copy 4x-2x hybrids indicated that reduction of transgene number in progeny, through meiotic segregation, could increase Cry3Aa expression. The results suggest that 4x-2x hybridization using single copy, male parents can result in high expressing, transgenic 4x-2x hybrids while segregating for a low frequency of non-transgenic hybrids that create a "refuge" to inhibit development of resistance to transgenes in pest populations.
Ph. D.

This thesis examines two topics related to the prevalence of unequal developmental outcomes among children of different socioeconomic backgrounds in Peru. The first topic focuses on the origins of these inequalities by measuring the relative importance of school and early childhood influences for the emergence of cognitive development gaps between urban and rural children. I use rich longitudinal information on cognitive achievement, household and school characteristics, and a novel decomposition strategy. Results reveal that observable school influences occurring between ages 6 and 8, account for a significant share (around 35% and no less than 28%) of the difference in cognitive skill. The share attributable to differences in the early childhood environment is important but no larger than 50%. I also discuss how the proposed decomposition strategy compares to other linear decomposition methods and why it is less prone to biases than those employed so far in the literature. The second topic is related to the effects and mechanisms behind early childhood development interventions that seek to improve the home environment through a change in parental behaviour. I use data on parenting practices and caregiver beliefs regarding the importance of parent-child interactions collected from the control and treatment groups of families randomized for the evaluation of a home-visiting programme recently launched at scale in rural Peru. I find that this intervention produced a positive effect on the quality of the home environment (d = 0.5; p < 0.01) and shifted caregiver behaviour increasing their participation in educational play activities with the child (d = 0.3; p < 0.01). I also explore the constraints that limit caregivers' behavioural change. I find that treatment effects are not significant among the poorest caregivers and that they exhibit a positive wealth gradient. Further, I find evidence suggesting that caregiver beliefs condition their responses to treatment.

Genomic imprinting is an epigenetic mechanism that leads to differential contributions of maternal and paternal alleles to offspring gene expression in parent-of-origin (POE) manner. Recently, parent-of-origin effects have attracted attention due to their potential contribution in the explanation of \textquotedblleft missing heritability\textquotedblright. We propose two different procedures for detecting the POEs in genome wide genotype data from related individuals (twins) when the parental origin cannot be inferred. In the first approach we suggest a multistep procedure to detect POEs based on a variance test to evaluate the gene expression heterogeneity between the homozygous and the heterozygous groups. The second method exploits a finite mixture of linear mixed models to propose a test for capturing the presence of POEs; the key idea is that in the case of POEs the population can be clustered in two different groups in which the reference allele is inherited by a different parent. The core advantage of the second method is that it is an integrated procedure developed specifically for the detection of the parental effects, while the first method a multistep procedure which results computationally faster. The performance of the proposed tests are evaluated through a wide simulation study. A discovery analysis on microarray gene expression data of the MuTHER study is performed by both methods.

L’asthme est une maladie inflammatoire chronique des voies respiratoires. C’est une maladie complexe et hétérogène, présentant un large spectre de manifestations cliniques dans lequel l’âge de début joue un rôle important. L’asthme résulte de nombreux facteurs génétiques et environnementaux et des interactions entre ces facteurs.Afin d’identifier de nouveaux gènes de susceptibilité à l’asthme et aux maladies allergiques, nous avons réalisé des études d’association pan-génomiques et de clonage positionnel en prenant en compte des mécanismes complexes : 1) empreinte parentale, 2) hétérogénéité de la maladie et 3) interactions gène-environnement.Nous avons tout d’abord réalisé une étude de clonage positionnel pour le phénotype asthme-plus-rhinite dans des familles d’origine européenne de quatre études indépendantes (770 familles recensées par un asthmatique et incluant 3200 sujets) en prenant en compte l'effet de l'origine parentale. L’intégration de données génétiques et épigénétiques, nous a permis d’identifier un mécanisme de médiation de l’effet d’un variant génétique transmis par le père sur le phénotype combiné asthme-plus-rhinite, par une méthylation différentielle d’un site CpG localisé dans le gène MTNR1A.Nous avons ensuite pris en compte la variabilité de l’âge de début de l'asthme dans la modélisation de la maladie par des méthodes d’analyse de survie et avons réalisé une méta-analyse d’études d'association pan-génomiques du délai de survenue de l’asthme dans neuf populations d’origine européenne (5462 asthmatiques et 8424 non asthmatiques). Nous avons ainsi identifié un nouveau locus de susceptibilité à l’asthme localisé dans la région 16q12. Nous avons également mis en évidence que les variants génétiques des régions 9p24 et 17q12-q21 étaient associés à un asthme précoce alors que les variants en 16q12 étaient associés à un asthme plus tardif. Enfin, nous avons réalisé une méta-analyse de cinq études d’interaction pan-génomiques du délai de survenue de l’asthme avec l’exposition au tabagisme passif dans l’enfance (3643 exposés et 5275 non-exposés). Nous avons montré que l’effet des variants génétiques des régions 9p24 et 17q12-q21 sur le délai de survenue de l’asthme était augmenté par l’exposition au tabagisme parental dans l’enfance.La prise en compte de mécanismes complexes dans les études génétiques, nous a permis d’identifier de nouveaux gènes de susceptibilité à l’asthme et de mieux comprendre les mécanismes physiopathologiques à l'origine de l’asthme et de son expression variable au cours de la vie
Asthma is a chronic airway inflammatory disease. It is a complex and heterogeneous disease with a wide spectrum of clinical manifestations in which the age of onset plays an important role. Asthma results from many genetic and environmental factors and from interactions between these factors.To identify new susceptibility genes to asthma and allergic diseases, we performed genome-wide association studies and positional cloning studies, while taking into account complex mechanisms: 1) parental imprinting, 2) heterogeneity of the disease and 3) gene-by-environment interactions.We first conducted a positional cloning study for asthma-plus-rhinitis in European families of four independent studies (770 families ascertained through an asthmatic and including 3200 subjects) while taking into account parent-of-origin effects. The integration of genetic and epigenetic data enabled us to identify that the effect of a paternally inherited genetic variant on the combined phenotype asthma-plus-rhinitis was mediated by a differentially methylated CpG site within MTNR1A gene. We then took into account the variability of age-of-asthma onset in the disease modeling using survival analysis methods and conducted a meta-analysis of genome-wide association studies of time-to-asthma onset in nine European populations (5,462 asthmatics and 8,424 non-asthmatics). We identified a new asthma susceptibility locus in 16q12. We also showed that genetic variants of 9p24 and 17q12-q21 regions were associated with early-onset asthma while 16q12 variants were associated with later-onset asthma. Finally, we performed a meta-analysis of five genome-wide interaction studies of time-to-asthma onset with early-life tobacco smoke exposure (3,643 exposed and 5,275 unexposed). We showed that the effect of genetic variants of 9p24 and 17q12-q21 regions on time-to-asthma onset was increased by early-life tobacco smoke exposure.Studying complex mechanisms in genetic studies led to identify new asthma susceptibility genes and to better understand the pathophysiological mechanisms underlying asthma and its variable expression throughout life

Lifelong development is largely programmed prenatally. Genetic and epigenetic factors, such as mitochondrial (mt) DNA variation and parent-of-origin effects, significantly contribute to variation in important prenatal phenotypes that determine lifetime development, including placenta and fetal musculoskeletal system. Such effects initially impact on transcriptome expression levels and eventually give rise to altered phenotypic traits. However, data regarding the overall magnitude and specificity of maternal and paternal genome effects in mammalian prenatal development is lacking. The present study aimed to dissect and quantify differential maternal and paternal genome effects on specific placental and fetal traits, and associated transcriptomic events which drive prenatal development. A large bovine fetal resource (n=73), consisting of both purebreds and reciprocal hybrids with Bos taurus taurus (Angus) and Bos taurus indicus (Brahman) (epi) genetics, was used in this study. We examined 41 gross- and histo-morphological placental and fetal traits, 51 fetal bone weight and geometry parameters, and 22 myofibre characteristics and muscle mass parameters using morphometrical and/or immunohistochemical methods. Expression of the long non-coding RNA H19 in fetal muscle was determined by real time quantitative PCR. Profiles of mRNA and microRNA expression were obtained with microarrays that contained 24,027 and 13,133 mammalian probe sets, respectively, to assess transcript abundances in fetal liver. Phenotypic data were analysed by Analysis of Variance (ANOVA) using general linear models with nested effects and transcriptome data were analysed with microarray ANOVA procedures. The analyses identified 49 significant placental and fetal traits, including five principal components representing 51 bone parameters, and H19 gene expression levels in muscle, with ANOVA model significance levels (P) ranging from 3×10⁻²-9×10⁻¹⁷. We showed that parental genomes contributed to the largest proportion of variation explained by linear models for a majority of placental and fetal traits. Fetal sex was the next most significant factor to explain variation in these traits and non-genetic maternal effects, such as post-conception weight gain and final maternal weight, explained the least amount of variation. Significant effects of the maternal genome (P<5×10⁻²-5×10⁻¹³) predominantly contributed to genetic variation in: (i) Gross- and histo-morphological placental traits and fetal organ weights (59.6−99.9%,); (ii) most extracted principle components (PCs) representing bone weight and geometry traits, including PC1/bone mass (74%), PC3/limb elongation (73%), PC4/flat bone elongation (74%) and PC5/axial skeletal growth (97%) and (iii) most myofibre characteristics including fast myofibre cross-sectional area (CSA, 93%), total cell CSA (82%), absolute mass of studied muscles (59-88%) and H19 transcript abundance in fetal muscle (76%). Conversely, significant paternal genome (P<4×10⁻²-7×10⁻⁸) predominantly contributed to genetic variation in: (i) Fetal fluids weight (73%), umbilical cord weight and length (73%), maternal placenta (70%) and umbilical cord (83%) efficiencies; (ii) PC2/limb ossification (95%) and (iii) Relative mass of studied muscles to fetal weight (54-97%). Further, using nested effects in ANOVA, we found that maternal genome strongly determined regressions between placental weights and umbilical cord traits (P<4×10⁻²-2×10⁻⁶), whereas paternal genome and/or fetal sex determined regressions between weight of fetus, fetal organ and fetal fluid s and umbilical cord traits (P<5×10⁻²-10×10⁻⁸). For fetal liver transcription profiles, maternal genome strongly affected expression levels of: (i) Twenty-four mRNA transcripts (false discovery rate, FDR adjusted P<4×10⁻²-10×10⁻⁶), 13 of which were located in the mt genome and (ii) ten autosomal non-coding RNA transcripts including mammalian SNORD113-9, small nucleolar (sno)RNA, MIR187 and MIR1973 microRNA (FDR adjusted P<5×10⁻²-8×10⁻³). Paternal genome moderately affected expression levels of: (i) Forty-seven autosomal mRNA transcripts (FDR adjusted, P<5×10⁻²-4×10⁻²) (ii) MIR184 microRNA transcripts in five mammalian species (FDR adjusted, P<5×10⁻²-4×10⁻²). Two significant coexpression networks, between 86 significant mRNAs and non-coding RNA transcripts, were also identified for differential maternal and paternal genome effects. Our results show, for the first time, that a wide range of phenotypic and molecular traits within the placental-fetal system are affected by differential maternal and paternal genome and fetal sex effects. Identified differential maternal and paternal genome effects on specific placental and fetal traits are consistent with expression patterns of parent-of-origin effects predicted by both conflict-of-interest and maternal-offspring coadapdation hypotheses, thereby providing important insights to accommodate both hypotheses that explain the evolutionary basis of genomic imprinting effects. Observed complex, and predominantly maternal genome, effects are suggested to result from interaction between epigenetic factors from nuclear and mt genomes via RNA interference. This is further evidence for complex epigenetic crosstalk and coordination that contributes to mammalian prenatal development. Identified morphological and transcriptional modules within the placental-fetal system help to provide a new level of understanding prenatal development, i.e., systematic integration of omics data. Detailed molecular profiles of all core tissues and organs are now required to elucidate genetic, epigenetic and non-genetic components and interactions that control variation in placental and fetal phenotype. Future studies linking genome and epigenome with phenome data covering the complete placental-fetal system will provide a new multi-layer picture of understanding coordination for molecular and phenotypic events driving mammalian prenatal development.
Thesis (Ph.D.) -- University of Adelaide, School of Animal and Veterinary Sciences , 2014.

abstract: In most diploid cells, autosomal genes are equally expressed from the paternal and maternal alleles resulting in biallelic expression. However, as an exception, there exists a small number of genes that show a pattern of monoallelic or biased-allele expression based on the allele’s parent-of-origin. This phenomenon is termed genomic imprinting and is an evolutionary paradox. The best explanation for imprinting is David Haig's kinship theory, which hypothesizes that monoallelic gene expression is largely the result of evolutionary conflict between males and females over maternal involvement in their offspring. One previous RNAseq study has investigated the presence of parent-of-origin effects, or imprinting, in the parasitic jewel wasp Nasonia vitripennis (N. vitripennis) and its sister species Nasonia giraulti (N. giraulti) to test the predictions of kinship theory in a non-eusocial species for comparison to a eusocial one. In order to continue to tease apart the connection between social and eusocial Hymenoptera, this study proposed a similar RNAseq study that attempted to reproduce these results in unique samples of reciprocal F1 Nasonia hybrids. Building a pseudo N. giraulti reference genome, differences were observed when aligning RNAseq reads to a N. vitripennis reference genome compared to aligning reads to a pseudo N. giraulti reference. As well, no evidence for parent-of-origin or imprinting patterns in adult Nasonia were found. These results demonstrated a species-of-origin effect. Importantly, the study continued to build a repository of support with the aim to elucidate the mechanisms behind imprinting in an excellent epigenetic model species, as it can also help with understanding the phenomenon of imprinting in complex human diseases.
Dissertation/Thesis
Masters Thesis Biology 2019

碩士
大同大學
事業經營學系(所)
103
Currently the consumer behavior theory and research belong to the scope of marketing, a purchase intention is an important concept in marketing science. If the company can grasp the purchase intention of consumer, they will know the future direction of the market and make profit. It is not discuss from internal message and external message in prior research. The so-called "internal message" is primarily individual buyers. "External message" is mainly external signs. It is a break away obeying parent’s generation. If the consumers’ economic capacity is enough, we will make decision by ourselves, but friends’ opinions still have a degree of influence. Therefore, the study decided to adopt self-construal (internal messages) and brand country-of-origin (external messages) as antecedent variables to explore purchase intention and simultaneously add parents and friends as moderators to discuss. This study adopts two experimental methods to collect empirical data. Experiment 1 adopted a 3 (Country-of-Origin: China, Taiwan or Korea)  2 (Self-Construal: Independent self-construal or Interdependent self-construal)  2 (Friends: Yes or Not), totally 337 valid questionnaires. Experiment 2 adopted a 3 (Country-of-Origin: China, Taiwan or Korea)  2 (Self-Construal: Independent self-construal or Interdependent self-construal)  2 (Parents: Yes or Not), totally 337 valid questionnaires. The results showed that country-of-origin and self-construal affect purchase intention; comparing to interdependent self-construal consumers, the consumers is higher. Moreover, experiment 1 supported that friends moderates the effect of country-of-origin. And partial supported that self-construal influence on purchase intention. Experiment 2 also supported that parents moderates the effect of country-of-origin. And partial supported that self-construal influence on purchase intention.