Dissertations / Theses on the topic 'Genetic architecture'
To see the other types of publications on this topic, follow the link: Genetic architecture.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Genetic architecture.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Griffin, Robert. "The genetic architecture of sexual dimorphism." Doctoral thesis, Uppsala universitet, Evolutionsbiologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-258986.
Full textAbstract:
Phenotypic differences between the sexes evolve largely because selection favours a different complement of traits in either sex. Theory suggests that, despite its frequency, sexual dimorphism should be generally constrained from evolving because the sexes share much of their genome. While selection can lead to adaptation in one sex, correlated responses to selection can be maladaptive in the other. In this thesis I use Drosophila to examine the extent to which the shared genome constrains the evolution of sexual dimorphism and whether the sex chromosomes might play a special role in resolving intralocus sexual conflict. Gene expression data shows that intersexual genetic correlations are generally high, suggesting that genes often affect both sexes. The intersexual genetic correlation is negatively associated with sex-bias in expression in D. melanogaster, and the rate of change in sex-bias between D. melanogaster and six closely related species, showing that a sex-specific genetic architecture is a prerequisite for the evolution of sex difference. In further studies I find that genetic variance affecting lifespan is found in the male-limited Y chromosome within a population, which could offer a route to the evolution of further sexual dimorphism in lifespan, though the amount of variance was small suggesting adaptive potential from standing genetic variance is limited. Genetic variance on the X chromosome is also expected to be depleted once the sex chromosomes evolve, but here I find no evidence of depletion in either sex. Dosage compensation does not appear to double the male X-linked genetic variance, but this effect may be complex to detect. Finally, the X chromosome appears to be enriched for sex-specific genetic variance, and the consequences of this are explored using a variety of analytical methods to test biologically meaningful aspects of G-matrix structure. In summary, this thesis suggests that the evolution of sexual dimorphism is generally constrained by the shared genome, but intralocus sexual conflict could be resolved by novel mutations on the Y chromosomes, and by standing sex-specific genetic variance on the X chromosome. It highlights a special role for the X chromosome in the evolution of sexual dimorphism.
2
Futema, M. "The genetic architecture of familial hypercholesterolaemia." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1417767/.
Full textAbstract:
Familial Hypercholesterolaemia (FH) is a common autosomal dominant disorder of the defective plasma clearance of LDL-cholesterol. Mutations in three genes, LDLR/APOB/PCSK9, can be detected in 60-90% of definite FH patients. DNA-based testing for FH mutations has important clinical utility and is recommended by the UK and European guidelines to identify affected relatives. This thesis aimed to determine the frequency and spectrum of FH mutations in two independent cohorts of FH patients (from one Oxford lipid clinic, and of Indian background). The FH mutation spectrum was shown to be highly heterogeneous and the mutation detection rate was significantly dependent on the pre-treatment total cholesterol and triglyceride levels. This project also validated the findings that a proportion of clinically diagnosed FH patients have a polygenic cause of hypercholesterolaemia due to an accumulation of common mild LDL-C-raising alleles by analysing LDL-C gene score in 88 mutation negative and 21 mutation positive FH patients, and by replicating the results in further 231 FH patients. A high-throughput DNA sequencing method was assessed as a novel diagnostic tool for detection of FH mutations, and compared it with the currently used methods. This highlighted the need for updating the current FH mutation screening methods as well as the need for more efficient bioinformatics for the next generation sequencing data analysis. Lastly, whole exome sequencing of 125 definite FH patients with no mutations detected in known genes was performed to identify novel monogenic causes of FH. Variants in two genes, CH25H and INSIG2, were identified as potential novel FH mutations. Overall, the results of this thesis demonstrate the heterogeneous FH aetiology and help to understand the genetic architecture of the disease.
3
Agarwala, Vineeta. "Integrating empirical data and population genetic simulations to study the genetic architecture of type 2 diabetes." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11120.
Full textAbstract:
Most common diseases have substantial heritable components but are characterized by complex inheritance patterns implicating numerous genetic and environmental factors. A longstanding goal of human genetics research is to delineate the genetic architecture of these traits - the number, frequencies, and effect sizes of disease-causing alleles - to inform mapping studies, elucidate mechanisms of disease, and guide development of targeted clinical therapies and diagnostics. Although vast empirical genetic data has now been collected for common diseases, different and contradictory hypotheses have been advocated about features of genetic architecture (e.g., the contribution of rare vs. common variants). Here, we present a framework which combines multiple empirical datasets and simulation studies to enable systematic testing of hypotheses about both global and locus-specific complex trait architecture. We apply this to type 2 diabetes (T2D).
4
Jain, Mahim. "Unraveling the genetic architecture of human traits." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509963.
Full text
5
Reid, Robert Alan. "Genetic engineering of plant architecture in wheat." Thesis, University of Leicester, 2003. http://hdl.handle.net/2381/29843.
Full textAbstract:
Particle bombardment of immature scutella was used to generate multiple lines of transgenic wheat with either PHY A, PHYB or PHYC from Arabidopsis or PHY A from oat.;Responses of segregating transgenic seedlings to cFR light were used as a screen for biologically active lines. The 'short coleoptile' phenotype under cFR was shown to segregate with the oat PHYA transgene and rtPCR detection of transcript. All of the transgenic lines containing the Arabidopsis PHYA and several oat PHYA lines demonstrated phenotypes indistinct to wild-type, possibly demonstrating transcriptional silencing.;Biologically active lines with Mendelian segregation ratios of 3:1 were selected for further analysis and homozygous individuals for each identified by PCR. Southern analysis of selected lines demonstrated that all originated from a distinct transformation event and harboured at least a single intact copy of the transgene. The complexity of gene integration was related to observed gene dosage and silencing effects.;Adult transgenic plants under white light with high R:FR ratio, demonstrated an increased chlorophyll content, a reduced production of superfluous tillers, a reduction in sensitivity to shortened day-length and an increased developmental rate leading to a reduction in days to heading.;The transgenic lines demonstrated an altered response to shade. In addition to the phenotypes observed under white light, plant height was significantly reduced and harvest index increased compared to the nulls, these responses were distinct to the those observed under white light and suggest an altered response to reduced R:FR.;The results suggest that oat PHYA is biologically active in transgenic wheat and that over-expressing PHYA alters the responses of etiolated seedlings to cFR, the light grown morphology and development of adult plants, and the responses of the plants to shade.
6
Merrill, Richard. "Genetic architecture and ecological speciation in Heliconius butterflies." Thesis, University of Cambridge, 2013. https://www.repository.cam.ac.uk/handle/1810/244602.
Full textAbstract:
It is now widely accepted that adaptation to different ecological niches can result in the evolution of new species. However, when gene flow persists speciation must overcome the antagonism between selection and recombination: Specifically, if gene flow persists, recombination will break down the genetic associations between alleles that characterise emerging species and cause reproductive isolation. Accordingly, genetic architectures that impede recombination can slow the breakdown of linkage disequilibrium and facilitate speciation. Mimicry in tropical butterflies has long been championed as an example of adaptation driving speciation. In the Neotropical genus Heliconius, distantly related pairs of unpalatable species often converge on the same bright warning-pattern to more efficiently advertise their distastefulness to predators. In contrast, closely related taxa often belong to different mimicry rings. The sister species, Heliconius melpomene and H. cydno are sympatric across much of Central and northern South America. Using artificial butterflies I reveal selection against non-mimetic hybrid colour patterns between these two species. These colour patterns are also used as mating cues and mimetic shifts may cause both pre-mating and post-mating isolation. However, shifts in colour pattern cannot drive reproductive isolation alone; rather, they must be accompanied by corresponding mate preferences. Associations between trait and preference loci may be broken down by mating and subsequent recombination. I demonstrate a genetic linkage between loci for both male and female mate preference and wing colour pattern in Heliconius cydno and H. melpomene. In addition, I present evidence for further associations between alleles affecting hybrid sterility and host-plant use and colour pattern loci. All this implies that linkage between traits that contribute to reproductive and ecological isolation is a general phenomenon in Heliconius with an underlying adaptive basis. Overall these results expose a genetic mechanism that, by impeding recombination, can facilitate speciation in the face of gene flow.
7
Dolgin, Elie. "The effects of breeding systems on genetic architecture." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/2487.
Full textAbstract:
Differences in reproductive strategies are a major factor influencing the patterns of genetic variability. Inbreeding and other non-recombining breeding systems can have profound effects on the efficacy of natural selection, which should be manifested in the patterns of genetic diversity within and between species. The impact of an organism’s breeding system can be investigated through a number of approaches. In this thesis, I use mathematical modelling, computer simulations, breeding schemes, quantitative life history measures, and molecular biological techniques to explore many of the consequences of breeding system evolution. Following a general introduction in Chapter 1, I explore the dynamics of transposable elements (TEs)—selfish mobile sequences of DNA that have deleterious effects upon their hosts. Sexual reproduction and recombination are important for constraining TE abundance, and in the absence of sex, an unchecked proliferation of TEs may cause a population to go extinct. In Chapter 2, I use a theoretical framework to analyze TE dynamics under asexual reproduction. Here, I show that while small populations are driven to extinction by element accumulation, large asexual populations can prevent this fate and be cured of vertically transmitted TEs. These results may help explain an "evolutionary scandal": the persistence of ancient asexual lineages, such as the bdelloid rotifers. In Chapter 3, I extend the computer simulations used in the previous chapter to explore the effects of reduced recombination on the distribution and abundance of TEs in sexual populations. I show that TEs become fixed as a result of Hill-Robertson effects in the form of Muller’s ratchet, but only in regions of extremely low recombination when excision is effectively absent and synergism between elements is weak. These results should help explain genomic patterns of TE distributions. In the remainder of the thesis, I turn to testing the genetic effects of androdioecy—the breeding system in which populations are comprised of separate male and hermaphrodite individuals—using the nematode Caenorhabditis elegans and related species. This unusual breeding system promotes high levels of inbreeding, yet males are maintained at appreciable frequencies. In Chapter 4, I measure lifehistory traits in the progeny of inbred versus outcrossed C. elegans and the related outcrossing species, C. remanei, to compare levels of inbreeding depression. I show that highly inbred C. remanei show dramatic reductions in brood size and relative fitness compared to outcrossed individuals, whereas pure strains of C. elegans performed better than crosses between strains, indicating outbreeding depression. The results are discussed in relation to the evolution of androdioecy and the effect of mating system on the level of inbreeding depression. Like C. elegans, C. briggsae reproduces by self-fertile hermaphrodites, and both species have similarly low levels of molecular diversity. But the global sampling of natural populations has been limited and geographically biased. In Chapter 5, I describe the first cultured isolates of C. elegans and C. briggsae from sub-Saharan Africa, characterize these samples for patterns of nucleotide polymorphism and vulva precursor cell lineage variation, and conduct a series of hybrid crosses in C. briggsae to test for genetic incompatibilities. With the new African isolates, I show distinct differences in levels of genetic and phenotypic diversity between the two species. Despite many similarities between C. elegans and C. briggsae, the results indicate that there may be more subtle, and previously unknown, differences in their natural histories. Finally, I return to the question of the impact of reduced recombination on TE dynamics in Chapter 6, by comparing population frequencies of TEs in natural populations of selfing and outcrossing Caenorhabditis species. I show that in the selfing species, C. elegans, transposons are less polymorphic and segregate at higher frequencies compared with the outcrossing species, C. remanei. Estimates of the intensity of selection based on the population frequencies of polymorphic elements suggest that transposons are selectively neutral in C. elegans, but subject to weak purifying selection in C. remanei. These results are consistent with a reduced efficacy of natural selection against transposable elements in selfing populations.
8
So, Hon-cheong, and 蘇漢昌. "Genetic architecture and risk prediction of complex diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B4452805X.
Full text
9
Wells, Rachel. "Genetic control of canopy architecture in Brassica napus." Thesis, University of East Anglia, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439928.
Full text
10
Liu, Jimmy Zhenli. "The genetic architecture of immune-mediated complex diseases." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708737.
Full text
11
Ali, Mobina Shaukat. "Genetic architecture of species level differences in Begonia Section Gireoudia." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/7606.
Full textAbstract:
Begonia is one of the ten largest plant genera and is found throughout the tropics. I have used Begonia section Gireoudia to study the genetics underlying vegetative diversity in tropical herbaceous plants. Section Gireoudia is a large Central American group. The section is remarkably diverse in morphology and habitat preference. It ranges from wet rainforests to seasonally dry forests. I have investigated variation in morphological, anatomical and ecophysiological differences for 21 species in Begonia section Gireoudia. Based on the observed variation, species in Begonia section Gireoudia form a complex and unique group that stands out from currently analysed taxa in the global scale of variation on the basis of leaf function and resource use strategy traits as well as their peculiar leaf anatomy. Traits directly related to leaf function such as photosynthesis and stomatal conductance has very low values which overlap with those of CAM and aquatic plants. Values for traits indicative of resource use such as leaf mass area (LMA) and leaf dry matter content (LDMC) are also very low in Begonia when compared with the values observed globally. The trait- trait correlations across the species in section Gireoudia were also investigated and revealed patterns in micromorphology and ecophysiology. Some of the traits measured are correlated with each other in apparently straightforward, well charaterised biological relationships e.g., the variation among Begonia species in stomatal conductance and net assimilation rate are positively correlated. On the other hand, the linkage of high Amass with high Nmass which is in large part the result of a direct causal relationship, has been observed at the global scale but this relationship is not significant in Begonia section Gireoudia. I examined B. plebeja and B. conchifolia, two very closely related though ecologically divergent species from Meso-America, in more detail. I detected significant differences between the species for a number of phenotypic variables which may be related to their habitat preferences. This suggested that environmental conditions have driven divergent evolution of phenotypic traits for these two species. Using a mapping population generated from hybrids between these two species I was able to examine the genetic basis of these differences. This revealed that although some traits (such as anthocyanin accumulation) appear to be under simple genetic control, most of the variation between species has complex genetic inheritance patterns. I used QTL analysis to identify significant QTLs for 20 physiological, anatomical and morphological traits which varied between these two species. Leaf shape traits appear to be largely influenced by a few loci of large effect, making these good potential targets for further analysis. The study also identified clusters of coincident QTLs for different correlated traits identifying pleiotropic genes or suites of linked loci.
12
Nag, Abhishek. "Understanding the genetic architecture of glaucoma and its endophenotypes." Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/understanding-the-genetic-architecture-of-glaucoma-and-its-endophenotypes(2cd26bc9-2015-45eb-b7d5-6007d2d99207).html.
Full textAbstract:
Heritability estimates for glaucoma and its endophenotypes [intraocular pressure (IOP) and vertical cup-to-disc ratio (VCDR)] indicate that genetic factors determine a significant part of the susceptibility to glaucoma or variance of its endophenotypes. Identification and characterization of glaucoma susceptibility genes will therefore help strengthen our understanding and provide insights into novel mechanisms underlying glaucoma pathogenesis. The GWAS era saw a surge in the identification of susceptibility genes for glaucoma and its endophenotypes. As has been the experience with most other complex human traits, the genetic variants identified so far collectively explain only a minority of glaucoma’s estimated heritability. The scope of this thesis is to understand the role of some of the possible determinants of the unexplained heritability of glaucoma using an endophenotype-based approach, which would in turn help build a more complete picture of its underlying genetic architecture. Findings of several individual study GWAS so far suggest that common genetic variants determine part of the genetic architecture of the glaucoma endophenotypes. In order to boost the power to detect some of the common genetic variants that might still remain unidentified, a large international collaborative effort named the International Glaucoma Genetics Consortium (IGGC) was established. Findings related to the investigation of the glaucoma endophenotypes in the IGGC have been described in this thesis. The role of structural genetic variation such as copy number variation (CNV) has been under-explored with relation to glaucoma. The hypothesis that CNVs might influence part of the susceptibility to glaucoma was therefore investigated and has been described in this thesis. Low frequency (rare) single nucleotide variants (SNVs) with intermediate effect size, which were neither common enough to be tagged in GWAS nor did they have effects strong enough to be captured by linkage studies, might determine a part of the unexplained genetic architecture of glaucoma. The role of this class of variants has been explored using a unique dataset of ~2000 subjects from the TwinsUK cohort that have had their whole genome sequenced as a part of the UK10K project. This thesis describes the various analytical strategies that have been explored to ascertain their role in relation to the glaucoma endophenotypes, and the findings pertaining to them. Finally, this thesis also discusses the potential implications of the novel findings obtained, and makes suggestions for future work in this field in order to build on our understanding of the genetic basis of glaucoma.
13
Young, Adrian. "The Evolutionary Feedback between Genetic Conflict and Genome Architecture." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11482.
Full textAbstract:
The advent of separate sexes set the stage for dramatic evolutionary innovation across a wide range of taxa. Much of this innovation is attributable to divergent evolutionary interests between now distinct sub-populations of males and females. Trade-offs inherent to these divergent life histories, coupled with a common genome, conspire to limit natural selection's ability to simultaneously maximize the fitness of both sexes. Such conflict between the sexes has therefore largely shaped the history of the genomes of sexual taxa. However, various aspects of the genomic environment—including genes' spatial distributions, abilities to regulate their expression, and rates of recombination—also feed back to influence future sex-specific evolutionary trajectories. Using various genomic resources and transcriptome sequences for the lab mouse, I test several theoretical predictions regarding this feedback between genetic conflict and features of genomic organization.
14
Kayihan, Gogce Ceren. "Genetic architecture of fungal disease traits in loblolly pine." [Gainesville, Fla.] : University of Florida, 2006. http://purl.fcla.edu/fcla/etd/UFE0015719.
Full text
15
Bolstad, Geir Hysing. "Evolution of Signals: Genetic Architecture, Natural Selection and Adaptive Accuracy." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for biologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-12514.
Full text
16
Sambandan, Deepa. "The Genetic Architecture of odor-guided behavior in Drosophila melanogaster." NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-06032008-131124/.
Full textAbstract:
Understanding the genetic architecture of complex traits requires identification of the underlying genes and characterization of gene-by-gene and genotype by environment interactions (GEI). Behaviors that mediate interactions between organisms and their environment are complex traits that are especially sensitive to environmental conditions. Drosophila melanogaster presents an opportunity to systematically dissect epistasis and GEI, since large numbers of genetically identical individuals can be reared under defined environmental conditions. The olfactory system of Drosophila and its behavioral response to odorants have been well characterized. Previous studies on olfactory behavior have shown that the genetic architecture of this model behavior depends on epistatic networks of pleiotropic genes. I have used P-element mutagenesis in a co-isogenic background to identify genes that contribute to olfactory behavior. I have demonstrated that the effects of the transposon insertions are often dependent on developmental stage and that hypomorphic mutations in developmental genes can elicit profound adult behavioral deficits. I also assessed epistasis among these genes by constructing all possible double heterozygotes and measuring avoidance responses at two odorant concentrations. I observed enhancer and suppressor effects among subsets of these genes, and surprisingly, these epistatic interactions shifted with changes in the concentration of the olfactory stimulus. I then assessed variation in olfactory behavior in a population of 41 wild-derived inbred lines and asked to what extent different larval rearing environments would influence adult olfactory behavior and whether GEI is a minor or major contributing source of phenotypic variation. My results show that about 50% of phenotypic variation in adult olfactory behavior is attributable to GEI. In contrast, transcriptional analysis revealed that only 20 genes show GEI at the level of gene expression (FDR<0.05), some of which are associated with physiological responses to environmental chemicals. Quantitative complementation tests with piggyBac-tagged mutants for two of these genes (CG9664 and Transferrin 1) demonstrate that genes that show transcriptional GEI are candidate genes for olfactory behavior, and that GEI at the level of gene expression is correlated with GEI at the level of phenotype.
17
Fournier, Téo. "Unraveling the genetic architecture of traits in natural yeast populations." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAJ073.
Full textAbstract:
Comprendre les règles contrôlant la diversité entre individus issus d’une même population est l’un des points centraux de la biologie moderne. Récemment, l'avènement des études d’association pan-génomique a permis de lier le génotype au phénotype au sein de populations. Cependant, une part importante de la variance phénotypique reste inexpliquée et est appelée héritabilité manquante. En combinant le modèle d’étude Saccharomyces cerevisiae, un design emprunté à la génétique classique et des stratégies de phénotypage et de génotypage à haut-débit, ce travail a pour objectif d’élargir notre compréhension des causes de cette héritabilité manquante à l’échelle de l’espèce. Nous avons donc pu quantifier l’impact des variants rares, obtenir une image globale du spectre de la complexité génétique des phénotypes ainsi que mesurer l’impact du fonds génétique sur cette complexité. Enfin, grâce à des techniques de séquençage utilisant de longs fragments d’ADN, une solide base pour l'identification de variants structuraux dans des populations naturelles de levures a été bâtie, permettant d’obtenir une première vue des effets phénotypiques de tels variantsUnderstanding the rules governing the astonishing diversity existing between individuals belonging to the same population has been one of the central role of biology. Recent years have seen the advent of genome-wide association studies to link genotype and phenotype at a population level. However, in most of the cases, an important amount of phenotypic variance remains unexplained and is called missing heritability. By combining the powerful model Saccharomyces cerevisiae, an elegant design borrowed to classical genetics and high-throughput strategies of genotyping and phenotyping, this work focused on increasing knowledge on the genetic architecture of traits and more precisely on some putative causes of this missing heritability at a species-wide level. Thus, we could quantify the effect of low frequency variants, obtain a global view of the genetic complexity spectrum as well as the impact of the genetic backgrounds on this complexity. Lastly, by using cutting edge long read sequencing strategies, a strong foundation for the identification of structural variants in natural population has been laid and allowed to a first view of their phenotypic effect
18
Zambrano, Mendoza Jose Luis. "Genetic Architecture of Resistance to Phylogenetically Diverse Viruses in Maize." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1373285155.
Full text
19
Duggan, Brendan Michael. "Genetic improvement of skeletal architecture and locomotion in domestic poultry." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31096.
Full textAbstract:
Breeding success in the broiler chicken has been accompanied by gait problems which are detrimental to productivity and welfare. Although these gait issues have not been reported to the same extent in Pekin ducks, there is concern that such problems will manifest if the duck continues on its current selection trajectory. In order to understand how changes in morphology due to selection have affected gait in both species, divergent lines were objectively assessed for gait using a pressure platform (12 birds per line at three, five and seven weeks of age). The broiler chicken was compared to the slower growing layer chicken and the Pekin duck to its slower growing ancestor, the mallard. Two breeding lines of Pekin duck were also assessed. After gait assessment, the leg bones (femur and tibiotarsus) were scanned by computed tomography to measure morphological changes which have occurred due to selection for high growth and meat yield. Results were analysed by ANOVA, accounting for age and sex. During walking, heavy lines walked at a slower velocity, displayed a wider stance and spent more time supporting their mass on both feet than their lighter conspecifics, strategies which are likely to improve balance. The foot angle while walking differed between lines; all duck lines rotated their feet internally whereas the layer chickens’ feet were aligned with the direction of travel. Conversely the broiler chicken rotated its feet externally by seven weeks of age. Morphologically, the main differences were between species. Duck lines reached adult leg size earlier than chickens, which may be a response to differing adaptive environments prior to domestication. This early cessation of bone growth in ducks may provide more opportunity for the bones to remodel to handle the loads imposed on them. Lower levels of porosity and a unique cortical architecture observed in ducks endow relatively greater bone strength. Bone curvature also differed between species; the tibiotarsus curved more laterally in ducks than in chickens and may be a swimming adaptation that hinders locomotion on land in the modern production bird. In order to improve the objectivity of selection for better gait in poultry, the genetic parameters of gait components selected on the basis of results in this thesis were estimated using a linear mixed model in a population of Pekin ducks of known pedigree. As they are a simpler measure, similar or improved heritability estimates were estimated for these gait components when compared with the standard commercial gait score which is based on a subjective view of walking ability. Intense selection for economic traits has altered gait in similar ways in both species. To improve gait in poultry, greater breeding success may be achieved by focussing on those components of gait which have changed through selection, rather than using a subjective overall visual gait score. Furthermore, in both species, adaptations for pre-domesticated life may have affected the ability with which the selected lines have accommodated their gait to other morphological changes associated with increasing body mass.
20
Martínez, Marigorta Urko 1983. "Genetic architecture of complex disease in humans :a cross-population exploration." Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/96909.
Full textAbstract:
The aetiology of common diseases is shaped by the effects of genetic and environmental factors. Big efforts have been devoted to unravel the genetic basis of disease with the hope that it will help to develop new therapeutic treatments and to achieve personalized medicine. With the development of high-throughput genotyping technologies, hundreds of association studies have described many loci associated to disease. However, the depiction of disease architecture remains incomplete. The aim of this work is to perform exhaustive comparisons across human populations to evaluate pressing questions. Our results provide new insights in the allele frequency of risk variants, their sharing across populations and the likely architecture of diseaseLa etiología de las enfermedades comunes está formada por factores genéticos y ambientales. Se ha puesto mucho empeño en describir sus bases genéticas. Este conocimiento será útil para desarrollar nuevas terapias y la medicina personalizada. Gracias a las técnicas de genotipado masivo, centenares de estudios de asociación han descrito una infinidad de genes asociados a enfermedad. Pese a ello, la arquitectura genética de las enfermedades no ha sido totalmente descrita. Esta tesis pretende llevar a cabo exhaustivas comparaciones entre poblaciones para responder diversas preguntas candentes. Nuestros resultados dan pistas sobre la frecuencia de los alelos de riesgo, su presencia entre poblaciones y la probable arquitectura de las enfermedades.
21
Al, Turki Saeed. "Integrated approaches to elucidate the genetic architecture of congenital heart defects." Thesis, University of Cambridge, 2014. https://www.repository.cam.ac.uk/handle/1810/245178.
Full textAbstract:
Congenital heart defects (CHD) are structural anomalies affecting the heart, are found in 1% of the population and arise during early stages of embryo development. Without surgical and medical interventions, most of the severe CHD cases would not survive after the first year of life. The improved health care for CHD patients has increased CHD prevalence significantly, and it has been estimated that the population of adults with CHD is growing ~5% per year. Understanding the causes of CHD would greatly help improve our knowledge of the pathophysiology, family counseling and planning and possibly prevention and treatment in the future. The aim of my thesis was to identify novel or known CHD genes enriched for rare coding genetic variants in isolated CHD cases and learn about the relative performance of different study designs. High-throughput next generation sequencing (NGS) was used to sequence all coding genes (whole exome) coupled with various analytical pipelines and tools to identify candidate genes in different family-based study designs. Since there is no general consensus on the underlying genetic model of isolated CHD, I developed a suite of software tools to enable different family-based exome analyses of de novo and inherited variants (chapter 2) and then piloted these tools in several gene discovery projects where the mode of inheritance was already known to identify previously described and novel pathogenic genes, before applying them to an analysis of families with two or more siblings with CHD. Based on the tools developed in chapter 2, I designed a two-stage study to investigate isolated parent-offspring trios with Tetralogy of Fallot (chapter 3). In the first stage, I used whole exome sequence data from 30 trios to identify genes with de novo coding variants. This analysis identified six de novo loss-of-function and 13 de novo missense variants. Only one gene showed recurrent de novo mutations in NOTCH1, a well known CHD gene that has mostly been associated with left ventricle outflow tract malformations (LVOT). Besides NOTCH1, the de novo analysis identified several possibly pathogenic novel genes such as ZMYM2 and ARHGAP35, that harbor de novo loss-of-function variants (frameshift and stop gain, respectively). In the second stage of the study, I designed custom baits to capture 122 candidate genes for additional sequencing using NGS in a larger sample size of 250 parent-offspring trios with isolated Tetralogy of Fallot and identified six de novo variants in four genes, half of them are loss-of-function variants. Both of NOTCH1 and its ligand JAG1 harbor two additional de novo mutations (two stop gains in NOTCH1 and one missense and a splice donor in JAG1). The analysis showed a strongly significant over-representation of de novo loss-of-function variants in NOTCH1 (P=3.8 ×10-9). To assess alternative family-based study design in CHD, I combined the analysis from 13 isolated parent-offspring trios with 112 unrelated index cases of isolated atrioventricular septal defects (AVSD) in chapter 4. Initially, I started with a case/control analysis to test the burden of rare missense variants in cases compared with 5,194 ethnically matching controls and identified the gene NR2F2 (Fisher exact test P=7.7×10-07, odds ratio=54). The de novo analysis in the AVSD trios identified two de novo missense variants in the same gene. NR2F2 encodes a pleiotropic developmental transcription factor, and decreased dosage of NR2F2 in mice has been shown to result in abnormal development of atrioventricular septa. The results from luciferase assays show that all coding sequence variants observed in patients significantly alter the activity of NR2F2 target promoters. My work has identified both known and novel CHD genes enriched for rare coding variants using next-generation sequencing data. I was able to show how using single or combined family-based study designs is an effective approach to study the genetic causes of isolated CHD subtypes. Despite the extreme heterogeneity of CHD, combining NGS data with the proper study design has proved to be an effective approach to identify novel and known CHD genes. Future studies with considerably larger sample sizes are required to yield deeper insights into the genetic causes of isolated CHD.
22
Mansoorkhani, Fereshteh Malekpoor. "Investigating the genetic and molecular basis of root architecture in tomato." Thesis, University of Nottingham, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.718989.
Full textAbstract:
Root system architecture (RSA) and morphology are important for plant productivity as many soil resources are unevenly distributed. RSA varies widely between species, individuals in a species and even within individual root systems. In recent years, the structure and function of plant root systems has received increasing attention. Many cultivated plants have undergone a reduction in genetic variability from ancestral forms, and this is particularly obvious in tomato whose history of domestication has significantly reduced the variation available in the cultivated tomato gene pool. However, substantial variation for root architecture and other traits still exists in related wild Solanum species. This root variability can be potentially used to breed new and improved tomato varieties. Quantitative Trait Loci (QTL) for root architecture and other important traits can be identified using available sets of tomato introgression lines, which were developed through a succession of backcrosses. The small green-fruited species Solanum pennellii is a distant sexually compatible relative of S. lycopersicum (domesticated tomato) native to the Andes mountains of South America. S. pennelli was used as a founding donor parent of the first tomato introgression (IL) population made available for interspecific QTL identification, cloning, and plant breeding. In this project, the S. pennellii IL population was used as the starting point to fine map QTL involved in the control of tomato root architecture. A large effect QTL was identified on the top of tomato chromosome 4. The QTL region enhanced root length and number of lateral roots. To fine map the underlying gene(s), approximately 8000 IL 4-1-1 F2 plants were screened to identify recombinants, leading to the generation of two small ILs (Q1120 and Q2173) harbouring the root system architecture (RSA) QTL. These recombinants delineated a mapping interval of 177kb containing 26 gene models. Analysis of the genes in the mapping interval indicated that several showed expression depending on the presence of an M82 or S.pennellii allele. Based on these and other criteria two genes were selected as RSA QTL candidates. These included a transcription factor belonging to the bHLH class and the gibberellin receptor GID1. Functional studies in Arabidopsis and tomato are in progress to validate the link between these genes and improved RSA.
23
Norman, Paul John. "Genetic architecture of the immune system in humans : natural killer cells." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396352.
Full text
24
Mapholi, Ntanganedzeni Olivia. "Exploring genetic architecture of tick resistance in South African Nguni cattle." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97945.
Full textAbstract:
Thesis (PhD)--Stellenbosch University, 2015.ENGLISH ABSTRACT: The broad objective of this study was to identify single nucleotide polymorphisms (SNP) markers associated with tick resistance in South African Nguni cattle and it was addressed by three specific objectives. The first objective was to assess tick load and prevalence in Nguni cattle in different agro-climatic regions of South Africa using tick count data collected monthly from 586 Nguni cattle reared under natural grazing conditions, over two years. Tick counts were assessed under natural challenge at ARC Roodeplaat and Loskop farms (warm climate), and Mukhuthali Nguni Community and University of Fort Hare farms (cool climate). The second objective was to estimate genetic parameters for tick counts in Nguni cattle. The third objective was to identify SNPs associated with tick resistance in Nguni cattle. Counts for each tick species were conducted on each animal in the herd once a month on different body locations, including the head, ears, neck, back, legs, belly, perineum and tail. Distribution of counts was determined using the PROC FREQ (SAS, 2002 - 2010). The tick counts were then analysed with the PROC GLM procedure using the two fixed effect models. Genetic parameters for log-transformed counts were estimated from univariate animal and sire models and bivariate sire models using the ASREML program. Animals were genotyped using Illumina BovineSNP50K assay. After Quality Control (call rate >90%, minor allele frequency > 0.02), 40 436 SNPs were retained for analysis. Association analysis for tick resistance was carried out using two approaches: genome-wide association (GWA) analysis using the GenABEL package and a Regional Heritability Mapping (RHM) analysis. Six tick species were identified: Amblyomma hebraeum (42%), Rhipicephalus evertsi evertsi (22%), Rhipicephalus (Boophilus) spp. (16%), Rhipicephalus appendiculatus (11%), Hyalomma marginatum (5%) and Rhipicephalus simus (4%). Tick infestation was significantly affected by location, season, year, month of counting and age of the animal. Loskop farm, as the warmest location, had the highest tick counts and also showed the largest variation in tick loads. Higher tick counts were also observed in the hot-dry (September to November) and hot-wet (December to February) seasons compared to the other seasons. Amblyomma hebraeum was the dominant tick species across all four locations. Heritability estimates for tick count varied according to season and trait (body part or tick species) and ranged from 0.01±0.01 to 0.26±0.01. Genetic correlations ranged from -0.79±0.33 to 1.00±0.00 among counts for different body parts and 0.00±0.00 to 0.99±0.00 among tick species. Phenotypic correlations ranged from 0.06±0.01 to 0.72±0.01 among body parts and 0.01±0.02 to 0.44±0.01 for tick species. Whole body count was highly correlated to the perineum and the belly. These two traits appear to be the most suitable surrogates for whole body count. Several genomic regions of interest were identified for different traits by both the GWA and RHM approaches. Three genome-wide significant regions on chromosomes 7, 10 and 19 were identified for total tick count on the head, total A. hebraeum ticks and for total number of A. hebraeum in the perineum region. Suggestive significant regions were identified on chromosomes 1, 3, 6, 7, 8, 10, 11, 12, 14, 15, 17, 19 and 26 for several of the tick traits analysed. The GWA approach identified more genomic regions than did the RHM approach. These findings provide information that would be useful in developing strategies for genetic improvement of tick resistance through selection. The chromosome regions identified as harbouring quantitative trait loci (QTL) underlying variation in tick burden form the basis for further analyses to identify specific candidate genes related to cattle tick resistance and provide the potential for marker-assisted selection in Nguni.
AFRIKAANSE OPSOMMING: Die doel van hierdie studie was om enkel nukleotied polimorfismes (ENPs) merkers te identifiseer wat verwant is aan bosluisweerstand in Suid-Afrikaanse Nguni beeste; dit is aangespreek deur drie doelwitte. Die eerste doelwit was om bosluislading en -voorkoms van bosluise in Nguni beeste in verskillende landbou-klimaatstreke van Suid-Afrika te bepaal deur die gebruik van bosluistelling data wat maandeliks van 586 Nguni beeste, grootgemaak op natuurlike weiding, oor 'n tydperk van twee jaar versamel was. Die tweede doelwit van die studie, was om die genetiese parameters te bepaal vir die bosluistellings in die Nguni beesras. Om hierdie doelwit aan te spreek, is vier verskillende datastelle onderskei in die bosluistelling data wat oor die twee jaar periode versamel was. Genetiese parameters is derhalwe beraam vir die telling van bosluise om sodoende die beste seisoen te identifiseer vir die insameling van bosluistelling data om ten einde strategieë te ontwikkel vir die genetiese seleksie vir vehoogde weerstand teen bosluise. Die derde doelwit was om ENP streke te identifiseer wat verband hou met bosluisweerstand in Nguni beeste. Verskillende bosluisspesies was getel op elke dier in die kudde een keer per maand op verskillende plekke op die liggaam, insluitend die kop, ore, nek, rug, bene, maag, perineum en stert. Bosluistelling data is ontleed met behulp van die SAS program om bosluislading variasie te bepaal. Genetiese parameter skattings vir log getransformeerde bosluistellings data was bereken vanaf twee-veranderlike vaar modelle en een-veranderlike dier- en vaar modelle met behulp van die ASREML program. Om ‘n genomiese wye assosiasie studie (GWAS) uit te voer, is DNS geïsoleer en genotipering gedoen met behulp van die Illumina BovineSNP50K toets. Na kwaliteit kontrole (oproep frekwensie>90%, klein alleelfrekwensie>0.02) is 40.436 ENPs behou vir ontleding. Assosiasie analise vir bosluisweerstand is uitgevoer met behulp twee benaderings, d.i. 'n genoom-wye assosiasie (GWA) analise met behulp van die GenABEL pakket en 'n plaaslike oorerflikheid karterings (POK) analise. Ses bosluisspesies is geïdentifiseer, d.i. Amblyomma hebraeum (42%), Rhipicephalus evertsi evertsi (22%), Rhipicephalus (Boophilus) spp. (16%), Rhipicephalus appendiculatus (11%), Hyalomma marginatum (5%) en Rhipicephalus simus (4%). Bosluis besmetting was beduidend beïnvloed deur die plek, seisoen, jaar, maand tel en ouderdom van die dier. Loskop plaas het die warmste weer ervaar en het die hoogste bosluis tellings en ook die grootste variasie in bosluislading gehad. Hoër bosluistellings is ook waargeneem in die warm droë (September tot November) en warm nat (Desember-Februarie) seisoene in vergelyking met die ander seisoene. Amblyomma hebraeum is geïdentifiseer as die mees dominante bosluisspesies oor al vier lokaliteite. Die voorkeur aanhegtingsarea vir die bosluise was onder die stert, perineum en maag areas op die liggaam. Die oorerflikheid beraming vir bosluistelling, soos beïnvloed deur die seisoen en eienskap (d.i. deel van die liggaam of bosluisspesies), het gewissel van 0.01±0.01 tot 0.26±0.01. Genetiese korrelasies het gewissel van -0.79±0.33 tot 1.04±0.01 vir bosluistellings op verskillende liggaamsdele en tussen 0.00±0.00 en 0.99±0.19 vir bosluisspesies. Fenotipiese korrelasies was laag tot matig en het gewissel van 0.06±0.01 tot 0.72±0.01 vir liggaamsdele en 0.01±0.02 to 0.44±0.01 vir bosluisspesies. Die datastel D wat September-Januarie bosluistellings bevat het die hoogste genetiese variasie aangedui. Heel liggaam bosluistellings was hoogs gekorreleerd met bosluistellings rondom die perineum en maag. Hierdie twee lokaliteite blyk die mees geskikte plaasvervanger vir die heel liggaam bosluistelling te wees. Verskeie genoom gebiede van belang is geïdentifiseer vir die verskillende eienskappe van beide die GWA en RHM benaderings. Drie genoom-wye beduidende streke (op chromosome 7, 10 en 19) is geïdentifiseer vir die totale bosluistelling op die kop, totale A. hebraeum bosluise en vir die totale aantal A. hebraeum in die perineum streek. Aanbevelende beduidende streke is geïdentifiseer op chromosome 1, 3, 6, 7, 8, 10, 11, 12, 14, 15, 17, 19 en 26 vir 'n paar van die bosluis eienskappe wat ontleed was. Die GWA benadering identifiseer meer genoom gebiede as die POK benadering. Hierdie bevindinge bied nuttige inligting vir die ontwikkeling van strategieë vir die genetiese verbetering van bosluisweerstand deur seleksie. Die chromosome streke hier geïdentifiseer is skuiling kwantitatiewe eienskap loki (KEL) vir die onderliggende variasie in bosluislading en vorm die basis vir verdere ontledings vir spesifieke kandidaat gene te identifiseer wat verband hou met die vee bosluisweerstand en bied die potensiaal vir merkerbemiddelde seleksie in Nguni.
25
Herzig, Anthony Francis. "Studying the genetic architecture of complex traits in a population isolate." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCC110.
Full textAbstract:
Mon projet de thèse vise à exploiter le potentiel des isolats de population pour étudier la composante génétique des maladies multifactorielles. En effet, les isolats peuvent faciliter l'identification des facteurs génétiques habituellement trop rares en population générale. Cette thèse est composée de deux études principalement : l'imputation génétique et l'analyse de l'héritabilité. Chacune de ces études ont été abordée sous deux angles : l’un théorique, s’appuyant sur une vaste étude de simulations basée sur les caractéristiques de la population isolée du Cilento, permettant d’évaluer des stratégies d’analyse et de déterminer la plus adéquate ; l’autre appliqué, s’appuyant sur l’analyse de données génétiques réelles issues de la même population.L'imputation génétique est une étape cruciale pour effectuer des analyses d'association dans un isolat et représente une méthode peu couteuse pour obtenir les séquences complètes du génome ou de l’exome des individus de la population. L'efficacité de cette approche dépend de la précision de l’imputation ; nous avons donc étudié plusieurs stratégies pour obtenir une précision d'imputation maximale dans un isolat. Nous avons montré que les logiciels utilisant des algorithmes qui s’appuient sur les caractéristiques particulières des isolats n’étaient pas, de façon inattendue, aussi performants que ceux conçus pour les populations générales. De plus, malgré la disponibilité de panels de référence publics contenant plusieurs milliers de chromosomes, nous avons confirmé qu’un panel de référence spécifique de la population d’étude, même de taille très réduite, était essentiel pour la qualité de l’imputation. Ceci était d’autant plus vrai pour les variantes rares.Pour de nombreux traits, il existe des discordances entre les estimations de l'héritabilité obtenues à partir d’individus apparentés et à partir d’individus non apparentés. En particulier, la plupart des chercheurs considère que les effets dominants (non additifs) ne jouent pas un rôle majeur malgré les résultats contrastés des études sur les isolats. Notre deuxième analyse a révélé des mécanismes possibles pour expliquer la disparité de ces estimations publiées entre populations isolées et populations générales. Cela nous a permis de faire des déductions intéressantes pour nos propres analyses dans le Cilento. En particulier, nous avons identifié la possibilité d'une composante de dominance non nulle pour les niveaux de lipoprotéines de basse densité (LDL). Cela nous a amenés à effectuer des analyses d'association pan-génomique des composantes additives et non-additives pour LDL dans le Cilento et nous avons pu identifier des gènes qui avaient déjà été liés au trait dans d'autres études.Dans le contexte de nos deux études, nous avons observé l'importance de conserver l'incertitude génotypique (dosage pour l’imputation, vraisemblance des génotypes pour les données de séquençage). Dans la perspective de cette thèse, nous avons proposé des moyens d’incorporer cette incertitude à certaines méthodes utilisées dans ce projet.Nos résultats concernant les stratégies d'imputation et l'analyse de l'héritabilité seront très utiles pour la poursuite de l'étude de l'isolat de Cilento. Mais, ils seront également instructifs pour les chercheurs travaillant sur d'autres populations isolées et également applicables plus généralement à l'étude des maladies complexesMy thesis project is concerned with tapping the potential of population isolates for the dissection of complex trait architecture. Specifically, isolates can aid the identification of variants that are usually rare in other populations. This thesis principally contains in depth investigations into genetic imputation and heritability analysis in isolates. We approached both of these studies from two main angles; first from a methodological standpoint where we created extensive simulation datasets in order to investigate how the specificities of an isolate should determine strategies for analyses. Secondly, we demonstrated such concepts through analysis of genetic data in the known isolate of Cilento. Imputation is a crucial step to performing association analyses in an isolate and represents a cost-efficient method for gaining dense genetic data for the population. The effectiveness of imputation is of course dependent on its accuracy. Hence, we investigated the wide range of possible strategies to gain maximal imputation accuracy in an isolate. We showed that software using algorithms which specifically evoke known characteristics of isolates were, unexpectedly, not as successful as those designed for general populations. We also demonstrated a very small study specific imputation reference panel performing very strongly in an isolate; particularly for rare variants. For many complex traits, there exist discordances between estimates of heritabilities from studies in closely related individuals and from studies on unrelated individuals. In particular, we noted that most researchers consider dominant (non-additive) genetic effects as unlikely to play a significant role despite contrasting results from previous studies on isolates. Our second analysis revealed possible mechanisms to explain such disparate published heritability estimates between isolated populations and general populations. This allowed us to make interesting deductions from our own heritability analyses of the Cilento dataset, including an indication of a non-null dominance component involved in the distribution of low-density lipoprotein level measurements (LDL). This led us to perform genome-wide association analyses of additive and non-additive components for LDL in Cilento and we were able to identify genes that had been previously linked to the trait in other studies. In the contexts of both of our studies, we observed the importance of retaining genotype uncertainty (genotype dosage following imputation or genotype likelihoods from sequencing data). As a prospective of this thesis, we have proposed ways to incorporate this uncertainty into certain methods used in this project. Our findings for imputation strategies and heritability analysis will be highly valuable for the continued study of the isolate of Cilento but will also be instructive to researchers working on other isolated populations and also applicable to the study of complex diseases in general
26
Pallares, Amaya Luisa Fernanda [Verfasser]. "Genetic architecture of craniofacial shape in the house mouse : a genetic and morphological perspective / Luisa Fernanda Pallares Amaya." Kiel : Universitätsbibliothek Kiel, 2015. http://d-nb.info/1076775578/34.
Full text
27
Mazzarotto, Francesco. "Characterization of the genetic architecture of dilated cardiomyopathy using families and cohorts." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/39047.
Full textAbstract:
Cardiomyopathies are the leading cause of heart transplantation in the developed world, and dilated cardiomyopathy accounts for an important proportion of all heart failure cases in large clinical trials. In spite of a strong genetic basis for dilated cardiomyopathy being demonstrated widely in the past two decades, 60% of familial cases remain unexplained. Dilated cardiomyopathy is characterized by marked genetic heterogeneity, with more than 60 individual genes reported to cause the disease, yet only one (TTN) explaining more than 10% of cases. Here, high-throughput sequencing data, advanced imaging techniques and bioinformatics analyses were used to dissect the genetic architecture of dilated cardiomyopathy, by measuring the contribution of single genes and multi-genic variation on disease risk and severity, and performing gene and variant discovery in affected families. Burden testing (using bespoke software developed in the R programming language for this study) and regression modelling were used to examine the genetic determinants of disease by comparing a cohort of disease cases (n=332) to ethnically matched, phenotypically characterised healthy controls (n=319). This produced a measure of the contribution of each gene to dilated cardiomyopathy, taking into account the background variation rate in the general population. Analyses of multi-genic interactions were also performed, and having detected the signature of additive effects of variation in multiple genes on both disease likelihood and severity, further analyses were performed to identify specific gene-gene interactions in causing dilated cardiomyopathy. Subsequently, variant prioritisation strategies were developed to identify, from whole-exome sequencing data, possible genetic causes of an unexplained and very severe form of early-onset dilated cardiomyopathy segregating in a family. This led to the identification of new candidate genes, which might contribute towards a genetic diagnosis in the analysed family and to new insights into the pathogenesis of dilated cardiomyopathy. Preparatory work in developing variant prioritisation pipelines from whole-exome sequencing data had been performed earlier, on families affected with various inherited arrhythmia syndromes.
28
Zofkova, Magdalena. "Evolutionary dynamics in ephemeral pools : inferences from genetic architecture of large branchiopods." University of Western Australia. School of Animal Biology, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0048.
Full textAbstract:
[Truncated abstract] I have evaluated the effects of different types of ephemeral pools on the evolutionary dynamics of two large branchiopods in Australia, the clam shrimp Lynceus and the fairy shrimp Branchinella longirostris. Both shrimps are passive dispersers, relying on their sexually produced resting eggs for continuity of populations in time and space, although their actual dispersal ability remains speculative. The two currently recognised species of the genus Lynceus (L. tatei and L. macleyanus) are widespread across Australia, and they occupy a wide range of ephemeral fresh water habitats, while the fairy shrimp Branchinella longirostris is endemic to rock pools on granite outcrops in south-western Australia. Samples of populations were collected from a total of 96 ephemeral pools at 80 locations in New South Wales, Northern Territory, Queensland, South Australia and Western Australia . . . This highlighted the contrast between the two species and their microhabitats, and implied that these microhabitats offered different opportunities for dispersal. These were identified as frequent disturbances of the clam shrimp’s egg-banks due to ‘wash-out’ effects during heavy rains and animal and human vectors attracted by the water stored in the deep pools. My comparative study shows that the difference in evolutionary dynamics observed between the two species was a consequence of their environmental interactions rather than of the microhabitats themselves. Similar to patterns detected in other passive dispersers with disjunct population distribution, evolutionary dynamics in Lynceus and B. longirostris seem to be a result of complex interactions among gene flow, population histories and ecology of their habitat. The results contribute to the emerging evidence that branchiopod crustaceans are poor dispersers and highlight the importance of local context in determining evolutionary processes within species.
29
Choudhry, Zia. "Use of multiple strategies to understand the complex genetic architecture of ADHD." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121214.
Full textAbstract:
Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent, clinically heterogeneous neurodevelopmental disorder with a complex etiology implicating both genetic and environmental factors. Although it is well accepted that multiple genes are involved in the pathophysiology of ADHD, no genetic risk variants have been identified beyond doubt. In addition, environmental factors, including, maternal smoking and maternal exposure to stress during pregnancy have been consistently associated with this disorder.This thesis will describe multiple genetic strategies that may help reduce the "clinical heterogeneity" and "etiological complexity" of ADHD phenotype facilitating the identification of genetic variants, which may help, in dissecting pathways to the disorder.1. By using the "endophenotypes" approach and selecting COMT gene, which is firmly implicated in the modulation of brain catecholamines, we found a tentative association between Catechol-O-Methyltransferase alleles/haplotypes and the modulation of Executive Functions in ADHD children.2. We used "gene/environment interplay" i.e. stratifying ADHD children based on exposure to maternal smoking during pregnancy and maternal stress during pregnancy and investigated the implication of latrophilin3 gene LPHN3, a candidate gene consistently shown to be involved in ADHD (based on linkage studies, and candidate association studies) in increasing the risk for ADHD. This approach allowed the uncovering of differential associations between single nucleotide polymorphisms (SNPs) within the LPHN3 and a number of endophenotypes in patients according to their exposure to maternal stress during pregnancy.3. "Comorbidity" with obesity was employed as a tool to index a more homogenous subgroup of ADHD children and facilitate the identification of genetic variants implicate in ADHD. Using this scheme, we comprehensively (behaviorally and clinically) characterized children with ADHD in relation to their BMI/weight categories. We showed that, self-regulation deficits, usually hypothesized to mediate obesity in children with ADHD, are not more present in children with ADHD and obesity compared to the non-obese ADHD children. Furthermore, in a group of children not exposed to maternal smoking during pregnancy, we observed a novel association between ADHD pertinent phenotypes and a Fat Mass and Obesity (FTO) gene polymorphism that has been strongly associated to obesity by genome-wide association studies (GWAS). In summary, this research work demonstrates the usefulness of multiple strategies to reduce the clinical heterogeneity and etiological complexity of ADHD which may facilitate identification of genetic risk variants and the interaction of these with environmental factors. This in turn may help in elucidating the pathophysiology of ADHD.Le trouble déficit de l'attention avec hyperactivité (TDAH) est un trouble neurodéveloppemental très répandu, ayant une présentation clinique hétérogène et une étiologie complexe impliquant des facteurs génétiques et environnementaux. Bien qu'il soit généralement admis que plusieurs gènes sont impliqués dans la physiopathologie du TDAH, aucune variante génétique augmentant le risque n'a été identifiée avec certitude. En outre, les facteurs environnementaux, y compris, le tabagisme maternel et l'exposition maternelle au stress pendant la grossesse ont été systématiquement associés à ce trouble. Cette thèse décrira comment l'utilisation de stratégies multiples mettant à profit les données épidémiologiques peut aider à réduire "l'hétérogénéité clinique" et la "complexité étiologique" du TDAH. Ces stratégies facilitent l'identification des variantes génétiques, qui à leur tour peuvent aider à disséquer les différentes trajectoires physiopathologiques conduisant au TDAH.1. En utilisant l'approche des "endophénotypes" cognitifs, et en sélectionnant le gèneCOMT (Catéchol-O-Méthyltransferase) qui est impliqué dans le métabolisme des neuroamines, nous avons identifié une association entre les allèles/haplotypes de ce gène et la modulation des certaines fonctions exécutive (EF) chez les enfants ayant le TDAH.2. Nous avons utilisé "la stratification" des enfants ayant le TDAH en fonction de l'exposition au tabagisme et au stress maternel pendant la grossesse pour investiguer l'implication du gène LPHN3, un gène candidat impliqués dans le TDAH (sur la base d'études de liaison et d'association). Cette stratégie a permis la découverte d'associations différentielles entre des polymorphismes (SNP) du gène LPHN3 et un certain nombre d'endophénotypes chez les patients en fonction de leur exposition au stress maternel pendant la grossesse.3. Enfin, nous avons utilisé la "comorbidité" fréquemment rapporté entre obésité etTDAH comme un outil pour indexer un sous-groupe plus homogène d'enfants TDAH et faciliter l'identification des variantes génétiques communes au TDAH et à l'obésité. Nous avons comparé des enfants atteints de TDAH catégorisés selon leur Indice de masse corporelle (IMC)/catégories de poids par rapport à leurs caractéristiques comportementales et cliniques. Nous avons montré que les déficits d'autorégulation, une hypothèse souvent avancée pour expliquer la grand prévalence de l'obésité chez les enfants TDAH, ne sont pas associés avec l'obésité observées chez les enfants TDAH. Dans un deuxième temps, nous avons exploré l'association entre des phénotypes pertinents au TDAH et un gène hautement impliqué dans la régulation de la masse adipeuse appelé FTO. Nous avons identifié une association hautement significative entre ce gène et un grands nombre de traits pertinent pour le TDAH, particulièrement chez les enfants qui n'out pas été exposés au tabagisme au cours de la grossesse.En conclusion, ce travail suggère que l'utilisation de plusieurs stratégies visant à réduire "l'hétérogénéité clinique" et "La complexité étiologique" du TDAH peuvent faciliter l'identification des variantes de risques génétiques et l'interaction de celles-ci avec les facteurs environnementaux, ce qui à son tour peut aider à élucider les mécanismes neurobiologiques qui mènent au TDAH.
30
Chaube, Pragya. "Genetic architecture of the shell characteristics in the marine snail Littorina saxatilis." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/23025/.
Full textAbstract:
Speciation is a key process underlying biodiversity. This process is facilitated by local adaptation, when divergent selection overcomes gene flow, resulting in the accumulation of reproductive barriers. Theory suggests that this accumulation is strongly dependent on the genetic architecture of the traits underlying local adaptation. The aim of this project was to investigate the genetic architecture of locally adaptive traits in the marine snail Littorina saxatilis. This marine snail (Littorina saxatilis) is an excellent model to study speciation and local adaptation. Two diverging ecotypes live a few metres apart in distinct habitats and face divergent selection pressures dominated by crab predation and wave action. The ecotypes have evolved traits to adapt locally that make them behaviourally and structurally distinct. The most observable differences are seen in the shell size, shape, colours and patterns. Despite the differences, the two ecotypes meet in narrow contact zones and hybridize. Intermediates between the two parental ecotypes are observed in a crab-wave environmental gradient across the hybrid zones. This situation provides an excellent opportunity to exploit the power of association mapping in the hybrid zone to elucidate the genetic architectures of the locally adaptive traits. However, a prerequisite for the application of evolutionary genetic approaches is a genomic toolbox. In Chapters 2 and 3, I describe the construction of a transcriptome assembly and high-density linkage map for this species. These genetic resources were utilized in the subsequent analyses and other studies in this system. In Chapter 4, I investigate the genetic architecture of the adaptive shell traits. Theory suggests that the ground colours or banding patterns possess Mendelian inheritance and may respond directly to selection or may be linked with genes that respond to the physical environment and may thus be affected by selection. Shell morphometric characters (size and shape) may have a more complex pattern of inheritance and tend to be responsive to the environmental conditions. Thus, shell characteristics are excellent to study divergent selection pressures and local adaptation while making it imperative to understand their underlying genetic architecture. In the current study, we applied association analysis to a single hybrid zone in Sweden to elucidate the genes underlying six shell phenotypic traits (size, shape, banding pattern, ground colours - beige, black and dark beige). We sampled individuals from the hybrid zone and implemented targeted capture-sequencing to obtain genotypic data. We identified loci associated with the black and beige ground colours and banding pattern of the shell. No significant associations with the shell shape and size were found which may suggest polygenic and complex architecture, consistent with the theoretical expectation. In addition, our analysis suggests a possible role for chromosomal inversion underlying locally adaptive traits. This thesis addressed longstanding questions regarding the genetic architecture of the adaptive shell traits in this organism and provides directions for the future follow-up studies. The genetic resources described in this thesis will assist the future studies that may address a wide-range of evolutionary questions in this species.
31
Zofkova, Magdalena. "Evolutionary dynamics in ephemeral pools : inferences from genetic architecture of large branchiopods /." Connect to this title, 2006. http://theses.library.uwa.edu.au/adt-WU2007.0048.
Full text
32
Davis, Eloiza Marie. "Changes in genetic architecture in a 'captive breeding program" of Drosophila melanogaster." Diss., Online access via UMI:, 2009.
Find full text
33
Sasabe, Masataka. "The genetic architecture underlying species differences in genital morphology of carabid beetles." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/120698.
Full text
34
O'Connor, Christine. "Dissecting the Genetic Architecture of Complex Traits in the Nematode Caenorhabditis remanei." Thesis, University of Oregon, 2018. http://hdl.handle.net/1794/23756.
Full textAbstract:
A central problem in evolutionary quantitative genetics has been to attempt to dissect the genetic basis of complex traits. A variety of inferential methods have been developed to probe this issue. Here, I use experimental evolution, next generation sequencing and standing genetic variation in the nematode Caenorhabditis remanei to dissect the genetic basis of two model complex traits: oxidative and heat stress response.
Pleiotropy, when one gene affects more than one trait, is an important phenomenon to understand when attempting to understand the genetic architecture of a complex trait. Previous work in the nematode C. elegans found that abiotic stress response is controlled by a handful of genes of major effect, and that mutations in one gene can affect the ability of the organism to respond to multiple types of stressors. I used experimental evolution to probe the extent of pleiotropy between the genes selected for resistance to one of two abiotic stressors: acute heat and oxidative. In contrast to expectations, I find that acute heat stress response and acute oxidative response are polygenic, complex traits. Additionally, I find that the evolved responses do not share a genetic basis. This lack of correlation is reflected at the levels of phenotype, gene expression and genomic response to selection.
In addition to the complex interactions within an organism, the genetic architecture of complex traits and response to selection are affected by population dynamics. Here, I investigate the effect of gene flow on patterns and extent of phenotypic and genetic divergence between populations in distinct environments – a standard lab environment and a chronic heat stress environment. Gene flow of lab-adapted individuals into chronic heat stress adapted populations did not affect phenotypic adaptation, but greatly decreased the number of genomic sites that responded to selection. These results fit predictions that gene flow of non-locally adapted individuals will create an additional barrier for local adaptation, and the strength of selection of locally adapted alleles must not only be greater than the strength of random effects, but also be stronger than the effects of gene flow.
This work includes unpublished co-authored material.2019-01-27
35
Finucane, Hilary Kiyo. "Functional and cross-trait genetic architecture of common diseases and complex traits." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/112906.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mathematics, 2017Cataloged from PDF version of thesis.
Includes bibliographical references (pages 201-245).
In this thesis, I introduce new methods for learning about diseases and traits from genetic data. First, I introduce a method for partitioning heritability by functional annotation from genome-wide association summary statistics, and I apply it to 17 diseases and traits and many different functional annotations. Next, I show how to apply this method to use gene expression data to identify diseaserelevant tissues and cell types. I next introduce a method for estimating genetic correlation from genome-wide association summary statistics and apply it to estimate genetic correlations between all pairs of 24 diseases and traits. Finally, I consider a model of disease subtypes and I show how to determine a lower bound on the sample size required to distinguish between two disease subtypes as a function of several parameters.
by Hilary Kiyo Finucane.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Mathematics
36
Leslie, Elizabeth Jane. "Advances in understanding the genetic architecture of cleft lip and palate disorders." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/3489.
Full textAbstract:
Orofacial clefts are a heterogeneous group of craniofacial malformations that affect the lip and/or palate and represent the most common craniofacial birth defect in humans. In 30% of patients the cleft is accompanied by additional physical or cognitive abnormalities. Hundreds of these clefting syndromes have been described, many of which have Mendelian inheritance patterns. The most common of these is Van der Woude syndrome (VWS), caused by mutations in the transcription factor IRF6 (Kondo et al. 2002). The other 70% of patients lack additional features and are considered nonsyndromic. The etiology of nonsyndromic clefts is complex and involves the combined action of multiple genetic variants interacting with environmental factors.
A common approach for identifying genetic risk factor for complex disorders such as nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the genome wide association study (GWAS). We pursued a locus on 1p22 shown to be associated with NSCL/P by Beaty et al. (2010). Through a combination of expression studies in a mouse model and mutation screening in NSCL/P patients, we identified ARHGAP29 as a novel gene for NSCL/P and the likely etiologic gene at this locus. We identified eight rare variants in NSCL/P patients absent in controls including a nonsense and a frameshift mutation. These rare variants are reminiscent of previous resequencing studies that reported rare coding mutations in 20 different candidate genes for NSCL/P. We reviewed these variants and compared them with variants found in over 7000 exomes from the 1000 Genomes Project (1kGP) and NHLBI Exome Sequencing Project (ESP) to identify the variants and genes most likely to contain etiologic rare variants. We found good support for a role for rare variants in NSCL/P, particularly for MSX1 and genes of the FGF signaling pathway.
We next performed several studies to understand the genetic architecture of syndromic forms of clefting, focusing on VWS and popliteal pterygium syndrome (PPS), which is allelic to VWS. We compiled all of the nearly 300 published IRF6 mutations and compared the distribution of these mutations with IRF6 variants obtained from the 1kGP and ESP exomes. We found that mutations causing VWS were significantly over-represented in the DNA-binding domain and for the most part were absent from control exomes, indicating that they are likely to be truly causative for VWS or PPS. These mutations in VWS and PPS only account for 70% of VWS and 97% of PPS. We next hypothesized that mutations in RIPK4, which causes an autosomal recessive pterygia syndrome, could underlie the remaining VWS and/or PPS cases. We found novel homozygous mutations in RIPK4 in two PPS patients. This result has significant clinical ramifications, as counseling of recurrence risk is very different for PPS patients whose disease is caused by dominant IRF6 mutations compared to recessive RIPK4 mutations.
Finally, to understand the variable expressivity of VWS and PPS we performed an association study to identify genetic modifiers. We also looked for genotype-phenotype correlations between the type and location of IRF6 mutations. Although we did not find strong evidence that the candidate genes we selected from GWAS of NSCL/P or other clefting syndromes are modifiers of the VWS or PPS phenotypes, several marginal associations suggest that members of the IRF6 gene regulatory network could act as modifiers. Finally, we found evidence of a larger genotype-phenotype correlation by demonstrating that mutation-negative VWS families have a deficiency of cleft lip phenotypes. Together this work has advanced our understanding of the genetic basis of this diverse set of cleft lip and palate disorders, informing both the biology of craniofacial development and the clinical care of patients affected by these disorders.
37
Le, Treut Guillaume. "Models of chromosome architecture and connection with the regulation of genetic expression." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS411/document.
Full textAbstract:
Plusieurs indices suggèrent que le repliement du chromosome et la régulation de l’expression génétique sont étroitement liés. Par exemple, la co-expression d’un grand nombre de gènes est favorisée par leur rapprochement dans l’espace cellulaire. En outre, le repliement du chromosome permet de faire émerger des structures fonctionnelles. Celles-ci peuvent être des amas condensés et fibrillaires, interdisant l’accès à l’ADN, ou au contraire des configurations plus ouvertes de l’ADN avec quelques amas globulaires, comme c’est le cas avec les usines de transcription. Bien que dissemblables au premier abord, de telles structures sont rendues possibles par l’existence de protéines bivalentes, capable d’apparier des régions parfois très éloignées sur la séquence d’ADN. Le système physique ainsi constitué du chromosome et de protéines bivalentes peut être très complexe. C’est pourquoi les mécanismes régissant le repliement du chromosome sont restés majoritairement incompris.Nous avons étudié des modèles d’architecture du chromosome en utilisant le formalisme de la physique statistique. Notre point de départ est la représentation du chromosome sous la forme d’un polymère rigide, pouvant interagir avec une solution de protéines liantes. Les structures résultant de ces interactions ont été caractérisées à l’équilibre thermodynamique. De plus, nous avons utilisé des simulations de dynamique Brownienne en complément des méthodes théoriques, car elles permettent de prendre en considération une plus grande complexité dans les phénomènes biologiques étudiés.Les principaux aboutissements de cette thèse ont été : (i) de fournir un modèle pour l’existence des usines de transcriptions caractérisées in vivo à l’aide de microscopie par fluorescence ; (ii) de proposer une explication physique pour une conjecture portant sur un mécanisme de régulation de la transcription impliquant la formation de boucles d’ADN en tête d’épingle sous l’effet de la protéine H-NS, qui a été émise suite à l’observation de ces boucles au microscope à force atomique ; (iii) de proposer un modèle du chromosome qui reproduise les contacts mesurés à l’aide des techniques Hi-C. Les conséquences de ces mécanismes sur la régulation de la transcription ont été systématiquement discutéesIncreasing evidences suggest that chromosome folding and genetic expression are intimately connected. For example, the co-expression of a large number of genes can benefit from their spatial co-localization in the cellular space. Furthermore, functional structures can result from the particular folding of the chromosome. These can be rather compact bundle-like aggregates that prevent the access to DNA, or in contrast, open coil configurations with several (presumably) globular clusters like transcription factories. Such phenomena have in common to result from the binding of divalent proteins that can bridge regions sometimes far away on the DNA sequence. The physical system consisting of the chromosome interacting with divalent proteins can be very complex. As such, most of the mechanisms responsible for chromosome folding and for the formation of functional structures have remained elusive.Using methods from statistical physics, we investigated models of chromosome architecture. A common denominator of our approach has been to represent the chromosome as a polymer with bending rigidity and consider its interaction with a solution of DNA-binding proteins. Structures entailed by the binding of such proteins were then characterized at the thermodynamical equilibrium. Furthermore, we complemented theoretical results with Brownian dynamics simulations, allowing to reproduce more of the biological complexity.The main contributions of this thesis have been: (i) to provide a model for the existence of transcrip- tion factories characterized in vivo with fluorescence microscopy; (ii) to propose a physical basis for a conjectured regulatory mechanism of the transcription involving the formation of DNA hairpin loops by the H-NS protein as characterized with atomic-force microscopy experiments; (iii) to propose a physical model of the chromosome that reproduces contacts measured in chromosome conformation capture (CCC) experiments. Consequences on the regulation of transcription are discussed in each of these studies
38
Fernandes, José Maria Veiga. "Improving direct solar radiation in complex building envelopes with a computational genetic algorithm." Diss., Restricted to subscribing institutions, 2007. http://proquest.umi.com/pqdweb?did=1417816821&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full text
39
Andrianasolo, Domohina Noromalala. "Génétique des populations et modèles d'architecture et de production végétale : application à la préservation des ressources génétiques des Mascarocoffea." Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20225.
Full textAbstract:
Les espèces de Mascarocoffea (61 sur 124 décrites endémiques de Madagascar) sont fortement menacées d'extinction à cause de la réduction considérable des surfaces forestières à Madagascar. En vue de leur préservation, l'évaluation du niveau de diversité dans la collection de Mascarocoffea de la station de Recherche du FOFIFA à Kianjavato comparé à celui de quatre populations en in situ a été faite. Le niveau de diversité des populations en collection est plus important que celui en in situ dont l'hétérozygotie observée est similaire avec une importante richesse allélique. La modélisation de la croissance et du développement des jeunes individus de ces populations par le modèle GreenLab a permis d'appréhender la mise en place de la structure de la plante en accord avec la variabilité architecturale interspécifique chez les populations étudiées à différents stades de développement. Un bon ajustement sur la croissance a été obtenu par la calibration des populations étudiées dans le dispositif expérimental. L'évolution de la variable clé du modèle GreenLab, le rapport source-puits (Q/D) en fonction du temps pour les 7 populations ajustées a montré que la production de beaucoup plus d'organes influence l'évolution du rapport Q/D au court du temps. Ce rapport affecte la taille des organes et l'architecture des Mascarocoffea. Un essai sur des individus adultes poussant dans des milieux différents (ex et in situ) dont les paramètres morphologiques, architecturaux et génétiques ont été déterminés dans cette étude, permettrait de déterminer la réponse des plantes selon l'environnement dans lequel elles poussent et de faire une optimisation du modèle. La détection des individus hybrides aussi bien in situ qu'en collection permet de voir ultérieurement la conséquence sur la structure de la plante et d'envisager d'intégrer les paramètres génétiques dans le modèle…Mascarocoffea species (61 / 124 described, endemics to Madagascar) are highly endangered because of the considerable Madagascar area forest reduction. For their preservation, assessment of the Mascarocoffea diversity level in the FOFIFA Kianjavato Collection Research Station compared to four in situ populations was made. The collection population's diversity level is larger than that in situ, observed heterozygosity is similar with a significant allelic richness. Modeling the young individuals in these populations' growth and development by the GreenLab model helped to understand the development of the plant structure in accordance with the interspecific architectural variability in studied populations at different development stages. A good fitting on growth was obtained on the populations studied in the experimental plot. The evolution of the GreenLab model key variable, the source-sink ratio (Q / D), showed that the production of many more organs influences the ratio Q / D evolution in time. This variable affects organ size and Mascarocoffea architecture. An essay on adult individuals growing in different environments (in and ex situ), whose morphological, genetic and architectural parameters were determined in this study, would allow the plants response in terms of architecture depending on the environment in which they grow and to optimize the model. The detection of hybrid individuals in both in situ and at the collection would detect hybrids characters on the plant structure and consider integrating genetic parameters in the model
40
Waksmunski, Andrea Rose. "From Variants to Pathways: Interrogating the Genetic Architecture of Age-Related Macular Degeneration." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1586371907365746.
Full text
41
Chutarat, Acharawan. "Experience of light : the use of an inverse method and a genetic algorithm in daylight design." Thesis, Massachusetts Institute of Technology, 2001. http://hdl.handle.net/1721.1/16775.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Architecture, 2001.Includes bibliographical references (p. 145-147).
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Integration of daylight availability in time and architectural space is a critical element in achieving optimal comfort and productivity, as well as in minimizing energy consumption. In recent years, there has been an increase in the demand of the better quality of the built environment. Accessibility and availability of information do not assurance success in design. There is a gap between available information and design team. A critical understanding of the issues that affects design and its process needs to be developed. Successful strategies require the participation of individual users and designers in configuring built environments and needs. Before proposing a new solution, success factors and methodology have been identified. There are many problems-solving techniques associated with design and delivery systems. Most popular techniques are forward methods and typically employed "trial and error" processes, attacking problems on the front end first. On the other hand, a problem-solving technique called the inverse method seems to be efficient. It starts with designer's goals and then identifies a design to meet those goals. In an effort to provide optimum choices in daylighting design, this thesis emphasizes the use of scientific-knowledge computational tools in the later stages of design employing the inverse method. The genetic algorithm (GA) is applied to search for optimal daylighting design strategies. A new design process has been created, developed, and implemented to increase design process efficiency and creativity. This thesis additionally presents a structured method for defining and evaluating multiple objectives. Objective measures are defined as maximized visual comfort and preferred lighting conditions. The thesis introduces a new daylight glare index (DGln). Further, a study has been conducted comparing subjective glare response in an office space with the DGln. Its correlation yields very promising results. Moreover, this research investigates several design problems, GA parameters, and processes for improving design results and efficiency. The most important aspect of GA and its application is the use of computation not as an analytical tool but rather as a vehicle to stimulate learning in the design process. Finally, ideas are presented for future work, based on the potential suggested by our findings.
by Acharawan Chutarat.
Ph.D.
42
Buys, Stefan. "Genetic algorithm for Artificial Neural Network training for the purpose of Automated Part Recognition." Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/d1008356.
Full textAbstract:
Object or part recognition is of major interest in industrial environments. Current methods implement expensive camera based solutions. There is a need for a cost effective alternative to be developed. One of the proposed methods is to overcome the hardware, camera, problem by implementing a software solution. Artificial Neural Networks (ANN) are to be used as the underlying intelligent software as they have high tolerance for noise and have the ability to generalize. A colleague has implemented a basic ANN based system comprising of an ANN and three cost effective laser distance sensors. However, the system is only able to identify 3 different parts and needed hard coding changes made by trial and error. This is not practical for industrial use in a production environment where there are a large quantity of different parts to be identified that change relatively regularly. The ability to easily train more parts is required. Difficulties associated with traditional mathematically guided training methods are discussed, which leads to the development of a Genetic Algorithm (GA) based evolutionary training method that overcomes these difficulties and makes accurate part recognition possible. An ANN hybridised with GA training is introduced and a general solution encoding scheme which is used to encode the required ANN connection weights. Experimental tests were performed in order to determine the ideal GA performance and control parameters as studies have indicated that different GA control parameters can lead to large differences in training accuracy. After performing these tests, the training accuracy was analyzed by investigation into GA performance as well as hardware based part recognition performance. This analysis identified the ideal GA control parameters when training an ANN for the purpose of part recognition and showed that the ANN generally trained well and could generalize well on data not presented to it during training.
43
Nakad, Rania [Verfasser]. "The genetic architecture of immune defence in the nematode Caenorhabditis elegans / Rania Nakad." Kiel : Universitätsbibliothek Kiel, 2017. http://d-nb.info/1136903305/34.
Full text
44
Adewoye, Adeolu Badi. "Genetic architecture and molecular mechanisms underlying light entrainment of the Drosophila circadian clock." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/10229.
Full textAbstract:
Despite significant progress in the understanding of how the circadian clock is entrained by light, the genetic architecture and molecular basis of this process are still largely unknown. This study was undertaken to identify biological pathways underlying light entrainment in Drosophila melanogaster. Complementary approaches that combined quantitative trait loci (QTL) mapping, complementation tests, and genome-wide gene expression profiling were used. One hundred and twenty-three recombinant inbred lines (RIL) were assayed for circadian photosensitivity. Composite interval mapping identified a single significant QTL. Quantitative deficiency complementation test refined this QTL interval into two smaller QTLs consisting of 140 candidate genes. Complementation tests with null mutant strains suggested segregating alleles of timeless and cycle may contribute to the variation in light response. In addition, two genes CG9879 and Lilliputian located within the QTL showed a significant differential expression in two RIL that were analysed by microarrays. Interestingly, Lilliputian interacts with several genes such as Shaggy and nejire which have been previously implicated in the circadian clock. Global profiling of gene expression following a light pulse at ZT15 revealed 209 differentially expressed genes in a laboratory strain (Canton-S). These genes are involved in several biological processes, however genes related to signal transduction, gene regulation, glutamate receptor activity, cellular communication and chromatin remodelling were statistically over-represented. RNA interference mediated knockdown further supported the role of these genes in the light response. Notable among these genes were nrv1, Neurofibromin 1, still life and Thor. In addition, the microarray experiments indicated that histone modifications may also play an important role in light entrainment of the clock. Consistently, an aberrant light response was found in various mutants and transgenic strains in which histone acetylation, de-acetylation, and methylation (of DNA and histones) are defective.
45
Riffo, Francisco Cubillios. "multi-parent crosses reveal the complex genetic architecture of polygenic traits in yeast." Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.537694.
Full text
46
Armstrong, Jenny. "The genetic architecture of a reproductive life-history trait in a wild passerine." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/11913/.
Full textAbstract:
Understanding the capacity for species to respond to changes in their environment and the rate at which they are able to do so is a key topic in evolutionary biology and of increasing importance in wildlife conservation and management. However the mechanisms involved in mediating these responses are poorly understood. Specifically, while reactive responses may be advantageous in the short term persistent directional changes in environmental conditions may require a more profound response in order for organisms to adapt and persist successfully. Here I use data from two long-term studies of the great tit Parus major and apply a range of statistical techniques to dissect the genetic architecture of laying date, a reproductive life-history trait, to discern the extent to which a genetic component of variation contributes to observed phenotypic variation. A heritable component of variation exists in both populations, but specific regions of the genome contributing to trait variation could not be detected by quantitative trait loci mapping (Chapters 2 & 3), genome-wide association (Chapters 2 & 3) or chromosome partitioning (Chapter 4) analyses. These findings are consistent with a highly polygenic basis for variation in laying date, variation maintained by many genes of small effect. Attempts to increase the statistical power by combining two phenotypic datasets to increase overall sample size (Chapter 3) and increasing marker density (Chapter 5) drew similar conclusions, with an absence of genome-wide significant QTL. Despite evidence of a strong association on chromosome 3 (Chapter 5), an overall lack of consistency between analyses and datasets on regions exhibiting the highest associations suggests that power to detect genomic regions, particularly when variation may be determined by many variants of small effect, is low. I conclude that while genetic variation exists, environmental factors and phenotypic plasticity likely account for much of the variation in laying date.
47
Novikova, Jekaterina. "Generic Cognitive Architecture for Real-Time, Embedded Cognitive Systems." Thesis, Blekinge Tekniska Högskola, Sektionen för datavetenskap och kommunikation, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-3889.
Full textAbstract:
The problem of integrated cognition , analyzed in the thesis, belongs to a multi-disciplinary area of cognitive engineering. The multi-disciplinary focusing on cognitive models and real-time embedded systems, such as mobile robots, helps to reveal a broader and deeper understanding of robotics as part of everyday life and society. Over the past decades many cognitive architectures have been proposed and steadily developed, based on different approaches and methodologies, but still current cognitive architectures are far from the goal of covering the requirements for general intelligence. Recent research in the area of evolutionary algorithms and genetic programming is used in this study as an inspiration for developing the new version of integrated cognitive architecture, and the knowledge of human brain structure and functions is applied to the architecture as well. In this study a survey of cognitive architectures is performed, a version of biologically inspired hybrid cognitive architecture is developed. This architecture is influenced by a contemporary research in evolutionary algorithms and genetic programming. Some modules of the architecture are applied to a mobile robot in a simulated environment.
48
Rünneburger, Estelle. "Évolution de la canalisation génétique dans un modèle quantitatif de réseau de régulation." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS547/document.
Full textAbstract:
La canalisation génétique est définie comme la capacité d’un organisme à avoir un développement constant en dépit des mutations qui l’affectent. A l’heure actuelle, trois hypothèses majoritaires cherchent à expliquer l’apparition de ce processus : évolutive, congruente et intrinsèque. Pour tester ces hypothèses, j’ai choisi d’étudier les réseaux de régulation. Pour cela, j’ai réutilisé un modèle théorique pour simuler in silico l’évolution des architectures génétiques, et les analyser par les outils de la génétique quantitative. J’ai d’abord étudié les comportements évolutifs de notre modèle et sa capacité de réponse à la sélection stabilisante. Outre l’analyse de l’impact des paramètres du modèle, j’ai mis en évidence l’absence d’équilibre mutation – sélection – dérive après des milliers de générations du fait de l’augmentation progressive de la canalisation. J’ai ensuite montré que les réseaux soumis à des mutations fréquentes et fortes, sélectionnés vers des optimums phénotypiques extrêmes, et dans lesquels certains gènes sont laissés libres d’évoluer sont plus aptes à faire évoluer de la canalisation génétique. Ces résultats nous ont amenés à proposer un double mécanisme impliqué dans l’évolution de la canalisation dans les réseaux de régulation : la réduction de la cible mutationnelle et la redondance de la régulation génique. Je termine ce manuscrit en présentant quelques pistes d’études complémentaires, portant notamment sur l’étude de la canalisation contre les perturbations environnementales et l’utilisation de modèles alternatifsGenetic canalization is defined as the capacity of an organism to undergo a normal development even when the genome is altered by mutations. Currently, three main hypotheses are prone to explain the apparition of such a process: evolutionary, congruent and intrinsic. To test these hypotheses, I chose to study gene regulatory networks. To this end, I used a theoretical model, ran in silico simulations, and analyzed the genetic architecture by using quantitative genetics tools. I first studied the evolutionary behavior of the model, and its capacity to respond to stabilizing selection. In addition to the sensitivity analysis to model parameters, I evidenced the absence of mutation-selection-drift equilibrium after several thousand generations, which reveals the evolution of canalization. I also showed that networks submitted to frequent and large mutations, and/or selected toward extreme phenotypic optima are more prone to evolve genetic canalization. This result leads us to propose a two-fold mechanism able to explain the evolution of canalization in gene regulatory networks: shrinkage of mutational targets and redundancy in genetic regulation. At the end of this manuscript, I propose some possible future studies, such as the study of canalization towards environmental perturbations, and use of alternative models
49
Alghamdi, Jahad. "Epidemiology and genetic architecture of blood pressure : a family based study of generation Scotland." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7540/.
Full textAbstract:
Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources.
50
Chan, Ying Leong. "Leveraging genetic association data to investigate the polygenic architecture of human traits and diseases." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11372.
Full textAbstract:
Many human traits and diseases have a polygenic architecture, where phenotype is partially determined by variation in many genes. These complex traits or diseases can be highly heritable and genome-wide association studies (GWAS) have been relatively successful in the identification of associated variants. However, these variants typically do not account for most of the heritability and thus, the genetic architecture remains uncertain.