Recent theoretical developments have led to a renewed interest in the potential role of chromosomal rearrangements in speciation. Australian morabine grasshoppers (genus Vandiemenella, viatica species group) provide an excellent study system to test this potential role, because they show extensive chromosomal variation: 12 chromosomal races/species with parapatric distributions. The research in this thesis involves the application of molecular genetic analyses to examine patterns of gene introgression among chromosomal races of Vandiemenella at three different spatial scales: local-scale hybrid zone analysis, island-scale phylogeography, and continental-scale phylogeography. The aims of these multi-scale analyses are to investigate whether chromosomal races represent genetically distinct taxa with limited gene flow, and to infer the historical biogeography of Vandiemenella and evolutionary origins of their parapatric distributions. Karyotype and 11 nuclear markers revealed a remarkably narrow hybrid zone with substantial linkage disequilibrium and strong deficits of heterozygotes between the chromosome races P24(XY) and viatica17 on Kangaroo Island, suggesting that the zone is maintained by a balance between dispersal and selection against hybrids (tension zone). Selection that maintains the stable hybrid zone is unlikely to be operating only on loci linked to rearranged chromosomes. Island-scale and continental-scale phylogeography using multiple nuclear markers indicated that Vandiemenella chromosome races/species generally represent genetically distinct taxa with reduced gene flow between them. In contrast, analyses of a mitochondrial gene showed the presence of distinctive and geographically localised phylogroups that do not correspond with the distribution of the Vandiemenella taxa. These discordant population genetic patterns are likely to result from introgressive hybridization between the taxa and range expansions and contractions. Overall, our molecular analyses favour the allopatric mode of diversification for the evolution of Vandiemenella and do not support the stasipatric speciation model of White (1978). Patterns of genetic differentiation between the chromosomal races analysed at three different spatial scales show dynamic responses of the grasshoppers to past climatic fluctuations, leading to opportunities for long-term isolation and allopatric fixation of new chromosome variants and molecular mutations at many loci. Further analyses are necessary to assess potential roles of chromosomal rearrangements in facilitating diversification in Vandiemenella by reducing recombination within the rearranged chromosome segments.

Gene regulatory networks are dynamic and continuously remodelled in response to internal and external stimuli. To understand how these networks alter cellular phenotype in response towards specific challenges, my first project sought to develop a methodology to explore how the strength of genetic interactions changes according to environmental context. Defined as sensitivity-based epistasis, the results obtained using this methodology were compared to those generated under the conventional fitness-based approach. By integrating this information with gene expression profiles and physical interaction datasets, we demonstrate that sensitivity-based epistasis specifically highlights genetic interactions with a dynamic component. Having investigated how an external stimulus regulates network dynamics, we next sought to understand of how genome positioning impacts transcription kinetics. This feat was accomplished by cloning two gene-reporter constructs, representing contrasting promoter architectures, across 128 loci along chromosome III in S.Cerevisiae. By comparing expression and noise measurements for promoters with “covered” and “open” chromatin structures against a stochastic model for eukaryotic gene expression, we demonstrate that while promoter structure regulates burst frequency (the rate of promoter activation), positional effects in turn appear to primarily modulate burst size (the number of mRNA produced per gene activation event). By integrating these datasets with information describing global chromatin structure, we suggest that the acetylation state of chromatin regulates burst size across the genome. Interestingly, this hypothesis is further supported by nicotinamide-mediated inhibition of Sir2 which would appear to modulate burst size globally across the genome.

Gene regulatory networks are dynamic and continuously remodelled in response to internal and external stimuli. To understand how these networks alter cellular phenotype in response towards specific challenges, my first project sought to develop a methodology to explore how the strength of genetic interactions changes according to environmental context. Defined as sensitivity-based epistasis, the results obtained using this methodology were compared to those generated under the conventional fitness-based approach. By integrating this information with gene expression profiles and physical interaction datasets, we demonstrate that sensitivity-based epistasis specifically highlights genetic interactions with a dynamic component. Having investigated how an external stimulus regulates network dynamics, we next sought to understand of how genome positioning impacts transcription kinetics. This feat was accomplished by cloning two gene-reporter constructs, representing contrasting promoter architectures, across 128 loci along chromosome III in S.Cerevisiae. By comparing expression and noise measurements for promoters with “covered” and “open” chromatin structures against a stochastic model for eukaryotic gene expression, we demonstrate that while promoter structure regulates burst frequency (the rate of promoter activation), positional effects in turn appear to primarily modulate burst size (the number of mRNA produced per gene activation event). By integrating these datasets with information describing global chromatin structure, we suggest that the acetylation state of chromatin regulates burst size across the genome. Interestingly, this hypothesis is further supported by nicotinamide-mediated inhibition of Sir2 which would appear to modulate burst size globally across the genome.

Syftet med studien är att undersöka hur en population av potentiellt blivande föräldrar i åldrarna 20-40 år önskar att handläggning av informationen kring ultraljudsmarkörer bör se ut. Studien utformades som en pilotstudie med bekvämlighetsurval, och en enkät med parametrar fördelade på 11 scenarion utarbetades. Enkäten delades ut på föreläsningar i och omkring Stockholm i april 2012. 49 kvinnor och 36 män deltog i undersökningen. Potentiellt blivande föräldrar vill ofta få information om upptäckta softmarkers. Dock svarar en betydande del av försökspersonerna att de för vissa scenarion inte vill ta del av all tillgänglig information. Flest vill ha information vid obotliga tillstånd och när markören sitter i fostrets hjärna eller hjärta. De scenarion där flest svarar att de inte vill bli informerade är då markören sitter i fostrets tarm eller skelett samt när tillståndet är bortbart. Signifikanta skillnader uppmättes mellan olika gruppers svar. Kvinnor svarar oftare än män att de inte vill ha information om funna softmarkers. Detsamma gäller för sambos/gifta när man jämför dem med de som är singlar. De som hade barn vill oftare inte veta om att en softmarker har upptäckts jämfört med de som inte har barn. / The aim of the study was to investigate how potential new parents aged 20-40 would prefer the information about soft markers to be handled. The study was designed as a pilot study, and a questionnaire was made with parameters divided into 11 scenarios. The questionnaire was handed out at lectures in the Stockholm area in April of 2012. Answers were analyzed in SPSS with chi-2 tests. 49 women and 36 men participated in the study. Potential new parents often wish to be informed of discovered soft markers. However, a significant portion of the participants say they prefer not to know about soft markers in their foetus in some scenarios. Scenarios where the condition is incurable or where the soft marker is placed in the brain or heart of the foetus are the ones where the most people say they want the information. A soft marker placed in the foetus’ intestines or skeleton is when the most people answer that they do not wish to recieve this information. Significant differences are seen between different groups. Women more often than men say they do not want information about a discovered soft marker. The same is true for those who are married or cohabitating when compared to singles. Those who are already parents want information about a soft marker to a lower degree than those who do not have children.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 118-130.

No description available.

Positioning of nucleosomes within the 30nm fiber is fundamental in understanding how DNA compaction regulates gene expression. Numerous studies have focused on determining the structure, however; no studies have assessed the structure genome-wide. In this study, a new in silico methodology for genome-wide nucleosome arrangement was assessed through the use of randomly generating in silico datasets for the solenoid, solenoid-interdigitated, cross-linker (with odd and even n), twisted ribbon, and twisted ribbon-interdigitated. A PERL script was written to generate six in silico datasets from the human genome based on patterns and probabilities of close proximity nucleosomes, and align various length terminal ends of the sequences to the genome. A graphical representation was used to assess the genome-wide pattern of paired sequence alignments for each model. Whole genome sequence data from formaldehyde fixed HeLa cells were filtered, aligned, and compared to the models. Lack of sufficient experimental alignments yielded inconclusive model determination. / DNA compaction and the 30nm chromatin fiber -- Development of in silico method for analysis of the 30nm fiber on a genome-wide scale -- Experimental analysis of the 30nm chromatin fiber on a genome-wide scale -- Future directions. / Department of Biology

Gene regulatory networks are dynamic and continuously remodelled in response to internal and external stimuli. To understand how these networks alter cellular phenotype in response towards specific challenges, my first project sought to develop a methodology to explore how the strength of genetic interactions changes according to environmental context. Defined as sensitivity-based epistasis, the results obtained using this methodology were compared to those generated under the conventional fitness-based approach. By integrating this information with gene expression profiles and physical interaction datasets, we demonstrate that sensitivity-based epistasis specifically highlights genetic interactions with a dynamic component. Having investigated how an external stimulus regulates network dynamics, we next sought to understand of how genome positioning impacts transcription kinetics. This feat was accomplished by cloning two gene-reporter constructs, representing contrasting promoter architectures, across 128 loci along chromosome III in S.Cerevisiae. By comparing expression and noise measurements for promoters with “covered” and “open” chromatin structures against a stochastic model for eukaryotic gene expression, we demonstrate that while promoter structure regulates burst frequency (the rate of promoter activation), positional effects in turn appear to primarily modulate burst size (the number of mRNA produced per gene activation event). By integrating these datasets with information describing global chromatin structure, we suggest that the acetylation state of chromatin regulates burst size across the genome. Interestingly, this hypothesis is further supported by nicotinamide-mediated inhibition of Sir2 which would appear to modulate burst size globally across the genome.

WWOX (WW domain-containing oxidoreductase) is a candidate tumor suppressor gene that has been shown to be involved in various cancers including breast, lung, prostate, gastric and hepatic. The Drosophila ortholog Wwox was identified and subjected to targeted ‘loss of function’ mutagenesis. The resulting mutants were found to be viable when homozygous with no obvious defects in the adult fly. As Wwox mutant flies were found to exhibit an increased sensitivity to ionising radiation (IR), a number of Wwox proteins specifically deleted or mutated at positions consisting of conserved functional protein motifs, or regions that are highly conserved among WWOX / Wwox homologs. The Wwox variants were tested for their ability to modify the IR sensitivity phenotype. In the course of this study, it was found that background mutations introduced during the generation of the mutant flies was responsible for the IR sensitivity phenotype. As a result, proteomic alterations resulting from changes in Wwox protein levels in Drosophila were investigated in order to ascertain the possible molecular functions of the Wwox protein. 2D-DIGE analysis was conducted on a number of different fly genotypes expressing differing levels of Wwox protein in both adult and embryonic flies. The proteomic changes resulting from lack of Wwox function as well as Wwox over-expression were detected with the proteins of interest identified by mass spectrometry (MS) using both MALDI-TOF/TOF-MS and LC-ESI-MS/MS. Label free quantitative MS analysis was also performed in order to determine the most abundant protein(s) in those spots found to contain multiple proteins. These proteomic studies identified changes in a wide variety of proteins with a significant number of metabolic proteins as well as proteins involved in oxidative stress response as a result of different levels of Wwox expression. Of particular interest, consistent changes in different isoforms of superoxide dismutase 1 (Sod1) were identified. Due to the known roles these proteins play in pro and anti-apoptotic pathways, it is possible that Sod1 and Wwox may work in concert to regulate the delicate balance of defence mechanisms in response to environmental stresses, particularly oxidative stress. The protein/gene targets identified in this work therefore offer some insights into normal Wwox function. / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2008

Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains vii, 124 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 116-124).