The ability to predict is one of the hallmarks of successful theories. Historically, the predictive power of biology has lagged behind disciplines like physics because the biological world is complex, challenging to quantify, and full of exceptions. However, in recent years the amount of available data has expanded exponentially and biological predictions based on this data become a possibility. The functional gene network is a quantitative way to integrate this data and a useful framework for making biological predictions. This study demonstrates that functional networks capture real biological insight and uses the network to predict both subcellular protein localization and the phenotypic outcome of gene knockouts. Furthermore, I use the functional network to evaluate genetic modules shared between diverse organisms that lead to orthologous phenotypes, many that are non-obvious. I show that the successful predictions of the functional network have broad applicability and implications that range from the design of large-scale biological experiments to the discovery of genes with potential roles in human disease. / text

For over a century, documented scientific research and debate has revolved around the therapeutic properties of the medicinal plant Echinacea angustifolia. With overwhelming evidence demonstrating the biological activity of its root phytochemical constituents, the genetic improvement of E. angustifolia by selecting phytochemically rich genotypes has garnered both scientific and commercial interest. This dissertation presents results of multi-disciplinary experiments intended to help establish scientifically based guidelines for breeding efforts aimed at developing therapeutically superior varieties of E. angustifolia in British Columbia. Cultivated E. angustifolia populations from British Columbia and Washington were grown in a common greenhouse environment to identify possible genetically superior populations with respect to root concentrations of therapeutically relevant caffeic acid derivatives (CAD) and alkamides. However, none of the studied cultivated E. angustifolia populations showed significant genetic differences in terms of root phytochemical traits. In the second part, an investigation into correlations between root and shoot phytochemical concentrations in field- and greenhouse-grown plants revealed that concentrations of therapeutically relevant marker compounds in shoots were generally poor predictors of concentrations in roots. Some weak yet significant positive correlations were observed between root and shoot concentrations of CADs but were inconsistent between the two environments. Significant genotype by environment interactions were documented for the first time in phytochemical traits of E. angustifolia in a study of five genetically homogeneous populations grown in three different environments, including 1 greenhouse and 2 field sites in British Columbia. For the final objective, in vitro bioassays showed that environmentally and genotypically related differences in concentrations of CADs and alkamides in E. angustifolia ethanolic root extracts did not translate into significant differences in their anti-inflammatory potential as measured by pro-inflammatory interleukin (IL-6 and IL-8) secretion in human bronchial epithelial (BEAS-2B) cells challenged with rhinovirus. When used in isolation however, pure tetraene alkamide showed a significant inhibitory effect on secretion, thereby further supporting the use of high alkamide production as a selection criterion for therapeutic E. angustifolia cultivar development. A series of recommendations derived from these findings are presented along with ideas for important future studies in the field of Echinacea research.

Managed pine forests are central to the economic vitality of the southeastern US. Over the past fifty years, the productivity of managed pine forests of this region have increased significantly with the development of new silvicultural technologies and the use of improved tree genetic material. Of the pine species present in the southeastern US, loblolly pine has arguably been the most intensively studied and widely planted by forest managers. Efficient operational deployment of improved genetic materials requires an understanding of how possible site conditions and silvicultural treatment may interact to affect maximum yield. There are a wide range of site conditions in the south as the result of regional climate gradients, soil type and soil drainage patterns. On the western edge of loblolly pine’s natural extent, Texas has a drier climate than areas to the east, and in Louisiana, there are also poorly drained Ultisols that are found in areas with little relief and are prone to flooding. However, on the basis of 10-year forest inventory data of pure-family plots from three different sites and under two levels of cultural regime intensity, my study found that superior genotype, Lob 5 from South Carolina, still showed best performance in the Western Gulf area, and high intensive treatment could improve stand growth and resistance to wind damage significantly. Further, my study compared the stand production and dynamics between pure- and mixed-family plots. I found that Lob 5 and Lob 4 showed the growth traits of competitive ideotype, and low intensive treatment increased the deployment effect significantly for competitive ideotype. Finally, my study examined leaf area index (LAI) and foliar nitrogen concentration (foliar N). The result showed that fast growing genotype had lower LAI and foliar N than slow growing one. It indicated that fast growing genotype had high resource use efficiency and nutrient requirement. This research provided critical information to guide industrial forest management in the WG (Western Gulf) area. First, introduced superior genotype continued to show good performance in this area. Second, combination of good genotype and high intensive treatment would increase plantation production significantly. Third, identification of ideotype would increase the accuracy of growth potential estimation in progeny test.

No description available.

The ability to metabolise drugs and achieve positive therapeutic outcomes is dependent on both genetic and environmental factors. The focus of this study was to determine the distribution and frequency of clinically relevant DME alleles and to assess the impact of these DME alleles on therapeutic outcomes in a cohort of 50 HIV-TB co-infected Zulu participants. PCR-RFLP was used to generate a genotypic profile of CYPIA2, 2C9, 2C19, 2E1, 3A4, MDR-1 and NAT-2. The distributions of the allelic frequencies were as follows. The CYPIA2 (A) - 50.7%, CYP2C9*2 — 100% and *3 — 56.2%, CYP2C19*2 — 35.4%, CYP2E1 (C2) — 28.4%, CYP3A4*1B (G) — 58.2%, MDR-1 (C3435T) - 16% and NAT-2 slow acetylators — 6.5%. Seventy-three percent of participants had prolonged TB therapy. Within this group, 82.9% of patient displayed wild type and 17.2% variant allele for CYP2E1 gene (p= 0.04) profile. In addition, all the slow acetylators in this study had prolonged TB therapy. In the MDR-1 gene, 87.5% showed wild type allele and 12.5% displayed the variant allele. Unsuccessful TB outcomes were also noted in 22% of this study population. In this group the variant allele was found to be dominant in CYPIA2, CYP3A4 and NAT-2, the opposite was seen in CYP2E1 and MDR-1. It was also interesting to note a similar genetic profile in the group that showed successful TB therapy outcomes. All participants had positive ARV treatment outcomes despite DME genotypic variations. However, 26% of all study participants experienced liver enzyme abnormalities. These findings concur with other studies regarding the ethnic distribution of DME alleles and evidence of an association between ART and TB therapeutic outcomes and DME genotype variation was inconclusive. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2007.

Campylobacter species are the primary cause of bacterial food-borne diarrhoea worldwide. Comparative genomic analyses of Campylobacter strains reveal genome plasticity providing insight into the evolution of virulence traits. The goal of this study was to identify genes important for infectivity and for naturally occurring variability in phenotypic traits in C. jejuni and C. coli strains. Transcriptome and phenotype analyses were conducted to determine if genetic and phenotypic characteristics could be attributed to the source of the strains. Isolates from water sources had higher biofilm formation than animal strains. Clinical strains had decreased sensitivity to hydrogen peroxide as well as increased adherence and invasion when compared to animal strains. A number of genetic differences were observed; however, without further analysis it is difficult to determine which of these impact virulence in Campylobacter. Ultimately, this project will lead to the identification of markers associated with strains of Campylobacter causing illness.

Two studies were conducted on gene mapping analysis. For the first study, genetic simulation experiments were conducted to address the effects of marker density, method of mapping analysis, and gaps in a marker map on the efficiency of QTL detection and the accuracy of QTL parameter estimation. The simulated genome consisted of seven chromosomes with seven or eight segregating QTL affecting the simulated quantitative trait. A set of six randomly segregating QTL outside the test region was consistently used to represent 40% of phenotypic variation. An individual QTL or a linkage block of two QTL on a target chromosome contributed 10% of phenotypic variation. The marker map was either dense (with markers every 4 cM) or sparse (with markers every 20 cM). The gap in the marker map was either 32 cM or 56 cM. Interval mapping and composite interval mapping were used to map QTL on the target chromosome. A dense map provided more power of QTL detection, better accuracy of QTL parameter estimation, and higher false-positive error rates for the target chromosome than a sparse map. Composite interval mapping provided more power of QTL detection, better accuracy of QTL parameter estimation, and lower false-positive error rates than interval mapping. Presence of a large gap in a marker map affected QTL detection and QTL parameter estimation for a QTL inside or near the gap. The use of a dense map with composite interval mapping was the most efficient combination tested in this study. For the second study, a mixed factorial regression model for interval mapping was developed for conducting QTL-by-environment interaction analysis and for providing inferences about QTL that are applicable beyond the environments used in the experiments. Genetic simulation was used to test the model for the power of detecting QTL-by-environment interaction and identifying the types of such interaction as crossover or non-crossover, and for the accuracy of estimating QTL parameters. The model prov

For over a century, documented scientific research and debate has revolved around the therapeutic properties of the medicinal plant Echinacea angustifolia. With overwhelming evidence demonstrating the biological activity of its root phytochemical constituents, the genetic improvement of E. angustifolia by selecting phytochemically rich genotypes has garnered both scientific and commercial interest. This dissertation presents results of multi-disciplinary experiments intended to help establish scientifically based guidelines for breeding efforts aimed at developing therapeutically superior varieties of E. angustifolia in British Columbia. Cultivated E. angustifolia populations from British Columbia and Washington were grown in a common greenhouse environment to identify possible genetically superior populations with respect to root concentrations of therapeutically relevant caffeic acid derivatives (CAD) and alkamides. However, none of the studied cultivated E. angustifolia populations showed significant genetic differences in terms of root phytochemical traits. In the second part, an investigation into correlations between root and shoot phytochemical concentrations in field- and greenhouse-grown plants revealed that concentrations of therapeutically relevant marker compounds in shoots were generally poor predictors of concentrations in roots. Some weak yet significant positive correlations were observed between root and shoot concentrations of CADs but were inconsistent between the two environments. Significant genotype by environment interactions were documented for the first time in phytochemical traits of E. angustifolia in a study of five genetically homogeneous populations grown in three different environments, including 1 greenhouse and 2 field sites in British Columbia. For the final objective, in vitro bioassays showed that environmentally and genotypically related differences in concentrations of CADs and alkamides in E. angustifolia ethanolic root extracts did not translate into significant differences in their anti-inflammatory potential as measured by pro-inflammatory interleukin (IL-6 and IL-8) secretion in human bronchial epithelial (BEAS-2B) cells challenged with rhinovirus. When used in isolation however, pure tetraene alkamide showed a significant inhibitory effect on secretion, thereby further supporting the use of high alkamide production as a selection criterion for therapeutic E. angustifolia cultivar development. A series of recommendations derived from these findings are presented along with ideas for important future studies in the field of Echinacea research.

Barley is the second largest grain crop produced in Australia and has two primary end uses. The first use is the premium market for malt and beer production. The second use is animal consumption. The quality of barley for the range of end uses is influenced by the cultivar itself as well as the growing environment. A detailed understanding of these factors at the genetic and biochemical levels was required to enable breeding program to select for quality improvement. A number of grain and end product quality traits were assessed for genetic and environmental affects as well as their interaction.Grain size has an important impact on quality and large plump grain is desirable for malt and feed quality. The results from the research conducted in this study clearly show that grain size was affected by cultivar and environmental conditions. Using screenings (< 2.2 mm) and retention (> 2.5mm) data provided information on how cultivars performed under a range of environmental conditions, which included irrigated (water unlimited) to terminal moisture stress (no in crop rain). The results showed a strong genetic component in the variation in grain size and it would be possible to select for increased grain size but also stable grain size when considering cultivars grown under adverse environmental conditions.The husk content in barley impacts on malt and feed quality. The results in this studied showed there were significant genetic effects as well as environments effects on the level of husk. In addition, it was identified that the genetic regions controlled husk expression were associated with two other quality traits, namely, resistance to kernel discolouration and resistance to pre-harvest sprouting (dormancy). These regions on chromosome 4H and 6H are also associated with previously identified dormancy genes.Hardness is a trait not usually considered when assessing barley quality but the results from this study showed there are differences in the level of barley hardness, as measured by three methods, as well as differences in the hardness gene sequence. The three hardness methods used showed that barley hardness could be measured independently of the method used, but also that there were significant genetic and environmental effects on hardness. However, the results from sequencing for allelic variation in the hardness genes showed that while there was polymorphism, and hance the transcribed protein had little effect on variation in quality. The cultivars used were malting and feed cultivars and a set of iv breeding lines targeted at malt quality. It may be possible to identify diverse haplotypes from the use of wild relatives or landraces.This study also investigated the variation in barley for cattle feed quality. Feed quality was determined using an in-sacco dry matter digestibility (ISDMD) assay in fistulated cows as well as three other laboratory assays, namely acid detergent fibre, starch and particle size. These four traits are then used to calculate Net Energy (NE) and Average Daily Gain (ADG). The results show that there were genetic and environmental effects on feed quality. The key trait was the ISDMD assay and there were significant differences between the cultivars tested. The data suggested feed quality was a measurable and definable attribute that could be used in breeding selection.The final aspect of this study compared the feed data obtained with routine malt quality traits, of friability and hot water extract. There were strong genetic and environmental effects. The malting cultivars generally had the highest level of ADG and NE. The results also showed that there were negative correlations between extract and husk, ISDMD and ADG. Positive correlations were shown between friability and hardness, extract and test weight, and there was only a slight correlation between average daily gain and extract.An important aspect of this study was the calculation of the genetic component for each trait. This was carried using spatial analysis of mixed models. It was necessary to use this approach so a true estimation of the genetic component could be calculated which would then allow for the calculation of heritability. In plant breeding, the cultivar is not a fixed effect but rather a random variable, hence it was not possible to use normal analysis of variation (ANOVA) models. Rather models were written with cultivars, like environment and field position, as random effects which will allow the effect of each random variable to be accounted for in the analysis. Best Linear Unbiased Predictions (BLUPs) are calculated and presented for all traits.For all the traits measured in this study, heritability values were calculated to ascertain the level of success in improving these traits through breeding. The range in heritability for grain size was 40 to 90%, husk 30 to 60%, hardness, 40 to 90%, feed quality traits 20 to 80% and malt quality traits 40 to 90%. Generally most traits exhibited a moderate to high level of heritability which indicated genetic improvement was possible through the use of appropriate genetic material.

Thesis (Ph.D.)--University of Melbourne, Dept. of Zoology, 2007. / Typescript. Includes bibliographical references (leaves 218-237).