Thesis MHSc(GenetCouns)--University of Melbourne, Murdoch's Children's Research Institute and Dept. of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, 2010. / Typescript. By Thesis only. Includes bibliographical references (p. 104-117)

Thesis (doctoral)--Konstanz Universität, Konstanz, 2009. / Includes bibliographical references (p. [354]-367) and index.

Since its introduction in 1960's, the model organism Caenorhabditis elegans has played a crucial role towards scientific discoveries because of its relatively simple anatomy, conserved biological mechanisms, and mapped genome. The organism also has a rapid generation time and produces a large number of isogenic progeny, making C. elegans an excellent system for conducting forward genetic screens. Conventional screening methods, however, are labor intensive and introduce potential experimental bias; typically, large-scale screens can take months to years. Thus, automated screening and characterization platforms can provide an opportunity to overcome this bottleneck. The objective of this thesis is to develop tools to perform rapid phenotypical characterization of C. elegans to enable automated genetic screening systems for neural development. To achieve this goal, I developed methods to increase throughput of worm handling using microfluidic devices and demonstrate software modules to phenotype unknown mutants using quantitative and morphological image analysis methods. Microfluidic devices are constructed from PDMS using established soft-lithography techniques. The emphasis on the simplification of existing designs greatly facilitates the adoption of our developed systems by other scientists. This thesis also includes image processing modules using various techniques to determine animal phenotypes. For example, we adapted standard thresholding methods to detect animal motor neurons, developed a modified granulometry algorithm to rapidly characterize large numbers of lipid droplets in 3D, and developed a probability model to determine neuronal process morphology. This work is significant because it increases current capabilities of screening small animals with morphological phenotypes by enhancing throughput and reducing human bias. Genes or gene functions that can be discovered using these methods can further elucidate mechanisms relevant to neural development, degeneration, maintenance, and function; these discoveries in turn can facilitate discoveries of potential therapeutic strategies for human neurological diseases.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Physiology, 2001. / Errata pasted onto back page. Bibliography: leaves 193-228.

Univ., Diss.--München, 2007.

Thesis (M.S.)--Brandeis University, 2009. / Title from PDF title page (viewed on May 29, 2009). Includes bibliographical references.

Thesis (M.S.)--Brandeis University, 2009. / Title from PDF title page (viewed on May 29, 2009). Includes bibliographical references.

Orientador: Iscia Lopes Cendes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T09:24:19Z (GMT). No. of bitstreams: 1 Gonsales_MarinaCoelho_M.pdf: 1544021 bytes, checksum: 7e7c28938a8217bf6f94e975f8778683 (MD5) Previous issue date: 2009 / Resumo: Dentre as epilepsias infantis, destacam-se a epilepsia mioclônica grave da infância (EMGI) e a epilepsia mioclônico-astática (EMA), as quais constituem os fenótipos mais graves do espectro da epilepsia generalizada com crises febris plus (EGCF+). Outra síndrome epiléptica importante é a epilepsia benigna da infância com espículas centro- temporais (EBIECT), que se destaca por ser a mais comum na infância. Avanços nos estudos de genética molecular levaram à descoberta de um gene responsável pelo espectro de fenótipos da EGCF+, o gene SCN1A, e um locus candidato para EBIECT na região 15q14. Os objetivos deste projeto foram realizar triagem de mutações em genes candidatos em pacientes com as epilepsias mencionadas e estabelecer possíveis correlações genótipo- fenótipo. Os genes estudados foram o SCN1A para EMGI e EMA e os genes CHRM5, CHRNA7 e CX36, localizados na região cromossômica 15q14, para EBIECT. A triagem de mutações foi realizada por meio da técnica de Denaturing High Performance Liquid Chromatography (DHPLC) e posterior sequenciamento automático dos fragmentos alterados. Foram estudados nove pacientes com EMGI, 12 com EMA e 27 com EBIECT. A análise de mutações no gene SCN1A revelou seis alterações potencialmente deletérias: as substituições c.829T>C, c.971A>C e c.5434T>C, que resultam em troca de resíduo de aminoácidos na proteína codificada, a inserção c.3719_3720insGATA, que promove alteração na matriz de leitura, e as alterações IVS4+1G>A e IVS8+3G>T, que se localizam em possíveis sítios doadores de splicing. As alterações foram encontradas apenas em pacientes com o fenótipo mais grave, a EMGI, nos quais ocorreram crises em vigência de febre baixa. A análise de mutações nos pacientes com EBIECT não revelou alterações potencialmente deletérias nos genes estudados. Com base nos resultados deste trabalho, podemos concluir que pelo fato de variantes potencialmente deletérias terem sido encontradas no gene SCN1A apenas em pacientes com EMGI, isso levanta a hipótese de que outro gene esteja envolvido na etiologia de EMA nos demais pacientes. O gene CHRM5 não parece estar envolvido com a etiologia de EBIECT em nossa amostra de pacientes. Também não foram encontradas alterações potencialmente deletérias nos genes CHRNA7 e CX36, mas os mesmos ainda não podem ser totalmente excluídos como envolvidos em EBIECT. / Abstract: Among the childhood epilepsies one important sub-group is the spectrum of generalized epilepsy with febrile seizures plus (GEFS+), which includes severe syndromes such as severe myoclonic epilepsy of infancy (SMEI) and myoclonic astatic epilepsy (MAE). Another important epileptic syndrome is benign childhood epilepsy with centrotemporal spikes (BCECTS), which is of particular interest for being the most common childhood epilepsy. Advances in molecular genetic studies led to the discovery of the SCN1A gene, responsible for the spectrum of GEFS+, and a candidate locus for BCECTS in the 15q14 region. The main objectives of this project were to screen candidate genes for mutations in a cohort of patients diagnosed with the epilepsies mentioned above, and to established genotype-phenotype correlations. We studied the SCN1A gene in patients with SMEI and MAE; and CHRM5, CHRNA7, and CX36 genes, located within the candidate region on chromosome 15q14, in patients with BCECTS. Mutation screening was performed using the denaturing high performance liquid chromatography (DHPLC) technique, with subsequent automatic sequencing of the altered fragments. We investigated 9 patients with SMEI, 12 with MAE and 27 with BCECTS. Analysis of the SCN1A gene revealed 6 potentially deleterious variants: substitutions c.829T>C, c.971A>C and c.5434T>C, leading to amino acid residue substitutions; insertion c.3719_3720insGATA, which promotes a frameshift; and alterations IVS4+1G>A and IVS8+3G>T, which possibly modify splicing donor sites. We found alterations only in patients with the most severe phenotype, SMEI, who had seizures during low temperature fever occur. Mutation analysis in patients diagnosed with BCECTS did not reveal potentially deleterious variants for the genes studied. As a result of our study, we can conclude that we only found potentially deleterious variants in the SCN1A gene among the patients studied. The fact that they were identified only in patients with SMEI provides evidence that another gene is likely to be involved in the etiology of MAE. The CHRM5 gene does not seem to be involved in the etiology of BCECTS in our patients. Even though no evidences supporting the pathologic role of CHRNA7 and CX36 genes were found, we still can not exclude them as involved in BCECTS. / Mestrado / Neurociencias / Mestre em Fisiopatologia Médica

Thesis (M. A.)--University of Canterbury, 2006. / Typescript (photocopy). Includes bibliographical references (leaves 118-130). Also available via the World Wide Web

Mutations in BRCA1 and BRCA2, the first two breast cancer susceptibility genes identified, carry as much as an 85% lifetime risk of developing breast, ovarian or other cancers. Genetic testing for mutations in these two genes has recently become commercially available. There have been varying amounts of psychological distress noted among women with a family history of breast cancer. Distress has been observed to impact psychological functioning, activities of daily living, and the practice of breast cancer surveillance behaviors. Within the genetic screening process, psychological distress has been shown to impact the decision to undergo genetic screening, the comprehension and retention of risk assessment information, as well as affecting the subject following the receipt of the genetic test results. Little work has been done to examine predictors of distress within at risk subjects. This study examines psychological distress among 52 community women presenting for BRCA1 and BRCA2 genetic mutation testing. Predictors of distress included family cancer history, education, age, Ashkenazi ethnicity, and Internality and Powerful Others Health Locus of Control. Vulnerable sub-groups of patients include younger women, women with higher levels of education and women of Ashkenazi ethnicity.