A quantitative trait locus (QTL) is the location of a gene that affects a trait that is measured on a quantitative (linear) scale. Many important agricultural traits such as weight gain, milk fat content and intramuscular fat in cattle are quantitative traits. There is a need to integrate genomic sequence data with QTL data and to develop an analytical tool to visualize the data. Without integration, application of this data to agricultural enterprise productivity will be slow and inefficient. My thesis presents a web-accessible tool called the Bovine QTL Viewer developed to solve this problem. It consists of an integrated database of bovine QTL and the QTL viewer to view the QTL and their relative chromosomal position. This tool generates dynamic and interactive images and supports research in the field of genomics. For this tool, the data is modeled and the QTL viewer is developed based on the requirements and feedback of experts in the field of bovine genomics.

The evaluation of environmental and genotypic effects on fruit physical and chemical characteristics enables assessment of the feasibility of selecting diploid and/or triploid cultivars for either specific or more diverse locations. Isolation and characterization of genes encoding enzymes in the carotenoid biosynthetic pathway provides fundamental genetic information which can facilitate breeding of watermelon cultivars having desirable flesh colors and enhanced beneficial carotenoids. For the environmental studies, the effects of deficit irrigation on lycopene content, total soluble solids, firmness, and yield of diploid and triploid watermelon were evaluated in different locations and growing seasons. Irrigation regimes were 1.0 evapotranspiration (ET), 0.75 ET, and 0.5 ET. To investigate if there is a consistent response in cultivars across diverse locations, studies were conducted in three distinct Texas regions. Deficit irrigation reduced total marketable yield, and increased the yield of small fruits. Location and irrigation regimes had major influences on yield. Soluble solids content increased with deficit irrigation at 0.5 ET in triploids, but not in diploids. Flesh firmness also increased in triploids compared to diploids. Lycopene content increased with maturity at all irrigation regimes and cultivars. This work confirms that deficit irrigation directly reduces yield, but does not reduce lycopene and fruit quality of the triploids used in this study. From the genetic studies, a total of eight genes encoding enzymes in the carotenoid biosynthetic pathway were isolated and characterized. Two members of the phytoene synthase (PSY) gene family were identified; PSY-A was expressed in all type of tissues, but PSY-B transcript was detected only in ovary, leaf, and root tissues. Gene expression of carotenoid isomerase (CRTISO) was not detected in salmon yellow. A color inheritance study of watermelon flesh indicated that a single gene might determine color difference between canary yellow and red without an inhibitory effect. A cleaved amplified polymorphic sequence (CAPS) marker developed from the SNP marker tagging two different lycopene β-cyclase (LCYB) alleles cosegregated perfectly with color phenotypes. It was concluded that color determination may be due to a reduced activity of LCYB enzyme in red, whereby a phenylalanine is conserved among canary yellow and valine is conserved among red watermelon.

Diss.--Marburg, 1999. / Bibliogr. p. 397-415.

Giessen, Universiẗat, Thesis (doctoral), 2002.

Assessment of risk has been a key element in efforts to identify factors associated with disease, to assess potential targets of therapy and enhance disease prevention and treatment. Considerable work has been done to develop methods to identify markers, construct risk prediction models and evaluate such models. This dissertation aims to develop robust approaches for these tasks. In Chapter 1, we present a robust, flexible yet powerful approach to identify genetic variants that are associated with disease risk in genome-wide association studies when some subjects are related. In Chapter 2, we focus on identifying important genes predictive of survival outcome when the number of covariates greatly exceeds the number of observations via a nonparametric transformation model. We propose a rank-based estimator that poses minimal assumptions and develop an efficient

Five breeding populations were created by crossing elite U.S. sorghum parental lines (RTx430, RTx436, BTx631, BTx635, and Tx2903) with 'Sureño', a dual purpose grain mold resistant sorghum cultivar. Molecular markers associated with five previously-reported quantitative trait loci (QTL) for grain mold resistance originating in 'Sureño' were used to determine if their presence enhanced selection for grain mold resistance in these populations. The allelic status of 87 F4 lines, with respect to these QTL, was determined using both simple sequence repeats (SSR) and amplified fragment length polymorphism (AFLP) markers. All 87 F4:5 lines and their parental lines, were evaluated for grain mold resistance in replicated trials in eight diverse environments in South and Central Texas during the summer of 2002. The effects of each allele from the grain mold resistant parent 'Sureño' were determined across and within all five populations, within individual environments, and in each population x environment combination. With a few exceptions, the QTL were effective in reducing grain mold susceptibility only within the RTx430/Sureño progeny, the identical cross that was used in the original mapping study. The results indicate that while that these alleles do confer additional grain mold resistance, they are only selectable in the original mapping population. This fact limits their potential usefulness in an applied breeding program.

Weed control in chickpea (Cicer arietinum L.) is challenging because of poor crop competition ability and limited herbicide options. Development of chickpea varieties with resistance to different herbicide modes of action would be desirable. Resistance to imidazolinone (IMI) herbicides in chickpea has been previously identified, but the genetic inheritance and the mechanism were unknown. In many plant species, IMI resistance is caused by point mutation(s) in the acetohydroxyacid synthase (AHAS) gene resulting in an amino acid substitution. This changes the enzyme configuration at the herbicide binding site, preventing the herbicide attachment to the molecule. The main research objective was to genetically characterize chickpea resistance to imidazolinone herbicides. Two homologous AHAS genes, namely AHAS1 and AHAS2 sharing 80% similarity were identified in the chickpea genome. A point mutation in AHAS1 at cytosine 675 thymine 675 resulting in an amino acid substitution from alanine 205 to valine 205 confers the resistance to imidazolinone in chickpea. A KASP marker targeting the point mutation was developed and effectively predicted the herbicide response in the RIL population. This same population was used in molecular mapping where the major locus for herbicide resistance was mapped to chromosome 5. Segregation analysis demonstrated that the resistance is inherited as a single gene in a semi-dominant fashion. To study the synteny of AHAS across plant species, lentil (Lens culinaris) AHAS1 was sequenced. The same mutation that confers the resistance to imidazolinone in chickpea was also found in lentil. Phylogenetic analysis indicated independent clustering of AHAS1 and AHAS2 across pulse species. In vivo and in vitro AHAS enzyme activity analysis showed inhibition of AHAS activity in the susceptible genotype CDC Frontier over time and with the increasing imidazolinone concentrations. In contrast, the resistant genotype CDC Cory did not show AHAS inhibition under the same treatments. In summary, the simple genetic inheritance and the availability of KASP marker could aid in the development of chickpea varieties with resistance to imidazolinone herbicide.

Background: Breast cancer is a complex disease, both phenotypically and etiologically. Accordingly, the responses to various treatments in the adjuvant setting among individuals vary considerably. There is a demand for tools that can distinguish patients who may benefit or may suffer from particular systemic treatments. We hypothesized that combination of data on genetic biomarkers with data from traditional clinical and pathophysiological (clinicopathologic) factors using traditional Cox model or Support Vector Machine (SVM) method, a new machine learning method, may provide a better tool for prediction of benefits to chemotherapy for the treatment of early breast cancer than using either biomarker or clinicopathologic data alone. Methods: This project included 531 patients from NCIC-CTG MA.5 trial who had data on both clinicopathologic factors, such as age, tumor size, ER status, type of surgery, tumor grade and lymph node involvement, and biomarkers assayed on tissue microarrays (TMAs), including HER2, p53, CA9, MEP21, clusterin, pAKT, COX2 and TOP2A. The Cox model and SVM methods were used to develop prognostic indices for relapse-free or overall survival with either data from TMAs and clinicopathologic assessments alone or their combination. The prognostic indices developed were then examined for their value as predictive classifiers for benefits from CEF treatment. The power of the predictive classifiers derived was evaluated and compared using the bootstrap approach. Results: None of the prognostic indices developed were found to have significant predictive value, although the prognostic index developed using SVM method based on only biomarkers yielded a marginal significant p-value (p=0.0527) for the interaction between classifier and treatment. In accordance with results published previously, the interaction between the classifier developed based on HER2 or TOP2A and treatment was significant (p=0.02 and 0.04 respectively). Comparisons based on the bootstrap approach indicate classifiers developed based on SVM performed better than those based on the Cox model method. Conclusions: Combination of data using biomarkers and clinical-pathological factors, and using either the traditional COX model method or the new machine learning method was not shown to perform better than two single previously known biomarkers in prediction of response to CEF treatment for early breast cancer. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2010-04-27 10:16:11.811

Contaminated environmental surfaces can be a means of transmission of Clostridium difficile spores in health-care facilities. The study objectives are to assess the value of the UV marker as an audit tool for improving housekeeping compliance and to compare microfiber and cotton cloths for removal of Clostridium difficile spores from surfaces. A lotion visible only under short-wave UV light (UV Marker) was applied to different surfaces within the patient’s washrooms on consecutive week days, over a twenty-four week period. The Study included three Arms: Arm one received feedback for 24 weeks , Arm two received feedback for the first 12 weeks and Arm three was given feedback for the last 12 weeks based on UV Marker results. The visual audit resulted in a cleaning compliance of 55%; whereas, feedback with the UV Marker led to a housekeeping compliance of 90%. The UV marker is a better audit tool than visual inspection for improving cleaning compliance of housekeeping staff. The use of microfiber cloths may enhance efficiency of microbial removal during surface cleaning.

Die Forschungsergebnisse der letzten Jahre beweisen, dass die Informationsverarbeitung im ZNS auf eine ausgewogene Interaktion zwischen den Neuronen und den Astrozyten im Sinne eines funktionellen Netzwerkes angewiesen ist. Allerdings liegen nur unzureichende Erkenntnisse über den strukturellen Charakter dieser symbiotischen Beziehung vor. Zu den grundlegenden Aufgaben der Astrozyten gehört die Modulation der synaptischen Aktivität von Neuronen, Aufrechterhaltung der extrazellulären Homoöstase, Ausbildung der Blut-Hirn-Schranke, Pufferung der lokalen Kaliumkonzentration und die Synthese von Zytokinen, Wachstumsfaktoren sowie Neurotransmittern. Ein Hauptbestandteil des Zytoskelettes der Astrozyten stellen die Intermediärfilamente (z.B. GFAP, Vimentin) dar. Funktionell dienen sie dem Aufbau von Zell-Zell- Kontakten, der Stabilisierung des Zytoskelettes und der Verankerung der Zellorganellen im Zytoplasma. Charakteristisch für den strukturellen Aufbau der Astrozyten ist das GFAP, welches hauptsächlich in den Zellfortsätzen lokalisiert ist. Aktuelle Forschungen legen nahe, dass es sowohl unter physiologischen Alterungsprozessen als auch im Rahmen von pathologischen Vorgängen im ZNS (beispielsweise chronischer Alkoholabusus, Alexanderkrankheit, Ischämien und Epilepsie) zu einem prozentualen Anstieg der GFAP-Expression kommt, wobei der Einfluss dieser erhöhten GFAP-Synthese auf die Funktionsfähigkeit der Astrozyten noch nicht umfassend geklärt werden konnte. Im Zentrum dieser Dissertation steht deshalb die Fragestellung, haben Alter und Intermediärfilamente (GFAP, Vimentin) Einfluss auf Morphologie und Zellzahl der Astrozyten im Hippokampus einer Maus? Initial erfolgte die Volumenbestimmung der Astrozytendomänen mittels LSM- Aufnahmen im Reflexionsmodus sowie Vermessung nach Bearbeitung der Präparate mit der Silber Imprägnationstechnik. Die Domäne eines Astrozyten stellt das von einem Astrozyten mit Soma und allen Fortsätzen okkupierte Volumen dar. Nach der Auswahl von S100ß als immunhistochemischen Astrozytenmarker wurde die Zellzählung in entsprechenden Hippokampusarealen durchgeführt. Aus den ermittelten Daten wurde rechnerisch der Überlappungsgrad der hippokampalen Astrozytendomänen bestimmt. Von entscheidendem Interesse war dabei die Möglichkeit einer Überschneidung benachbarter Astrozytendomänen. Aus den Messungen resultiert ein ca 1,6 fach grösseres Volumen der Wildtyp-Tiere im Vergleich zu den Doppel-knock-out-Mäusen. Im Gegensatz dazu zeigten die Ergebnisse der Zellzählung sowohl in der Kontrollgruppe als auch in der Gruppe der Versuchstiere eine vergleichbare Astrozytenanzahl pro mm3. Entsprechend lag der Überlappungsfaktor bei den Doppel-Knock-out-Tieren (0,49) unter dem der Wildtyp-Tiere (0,7). Die abschließende Auswertung erbrachte in allen Untersuchungsgruppen einen Überlappungsfaktor < 1. Ausgehend von der essentiellen Bedeutung der Astrozyten für die Funktionsfähigkeit der Nervenzellen käme es z.B. im Rahmen pathologischer Prozesse, welche mit Gliazellschäden einhergehen, bei einem Überlappungsfaktor < 1 zu erheblichen Engpässen in der neuronalen Versorgung, sowie in der Kompensation äußerer Einflüsse. Die Wahrscheinlichkeit irreversibler Schädigung der Nervenzellen steigt.