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

It is increasingly recognised that individual risk of cancer may be related to genetically determined differences in the ability of cells to identify and repair DNA damage. Cell cycle based assays of chromosomal radiosensitivity provide the greatest power for discriminating differences in response to DNA damage and it has been suggested that individuals who are genetically susceptible to cancer show increased chromosomal radiosensitivity. The relationship between chromosomal radiosensitivity and early onset cancer was investigated in a population of Danish survivors of childhood and adolescent cancer and a control group comprising of their partners using the G₂ assay of chromosomal radiosensitivity. Heritability was also examined in the offspring. No significant differences in radiosensitivity profiles were found between partner controls and either the cancer survivors or offspring. However, when compared to the Westlakes Research Institute control population, significant differences were observed with the cancer survivors (P = 0.002) and offspring (P < 0.001), supporting an association of chromosomal radiosensitivity with cancer predisposition. Heritability studies suggested the majority of phenotypic variance of chromosomal radiosensitivity was attributable to a putative major gene locus with dominant effect. Since G2 chromosomal radiosensitivity indirectly measures the ability of cells to repair DNA damage induced by ionising radiation exposure, variants in DNA repair genes may explain inter-individual variation observed. Sixteen polymorphisms in nine genes from four DNA repair pathways were investigated. Genotype frequencies at the Asp148Glu polymorphism were associated with childhood cancer in survivors. Analysis of variance and FBAT analysis suggested significant associations at both the Thr241Met and Ser326Cys polymorphism sites with G₂ radiosensitivity, but neither remained significant after multiple-test adjustment. This study invites further exploration of the predictive capacity of G₂ chromosomal radiosensitivity in cancer predisposition. Clearly, further work is needed to correlate radiosensitivity with genetic polymorphisms, which may underlie cancer susceptibility and variation in radiosensitivity.

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Pathology / Master / Master of Philosophy

published_or_final_version / Obstetrics and Gynaecology / Doctoral / Doctor of Philosophy

The research efforts refer to tracking homologus loci in the chromosomes of a pair of a species. The purpose is to infer the extent of maximum syntenic correlation when an exhaustive set of orthologs of the species are searched. Relevant bioinformatic analyses use comparative mapping of conserved synteny via Oxford grid. In medical diagnostic efforts, deducing such synteny correlation can help screening chromosomal aberration in genetic disorder pathology. Objectively, the present study addresses: (i) Cytogenetic framework of syntenic correlation and, (ii) applying information-theoretics to determine entropy-dictated synteny across an exhaustive set of orthologs of the test pairs of species. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Cytogenetics is a study on the genetic considerations associated with structural and functional aspects of the cells with reference to chromosomal inclusions. Chromosomes are structures within the cells containing body's information in the form of strings of DNA. When atypical version or structural abnormality in one or more chromosomes prevails, it is defined as chromosomal aberrations (CA) depicting certain genetic pathogeny (known as genetic disorders). The present study assumes the presence of normal and abnormal chromosomal sets in varying proportions in the cytogenetic complex ; and, stochastical mixture theory is invoked to ascertain the information redundancy as a function of fractional abnormal chromosome population. This bioinformatic measure of redundancy is indicated as a track-parameter towards the progression of genetic disorder, for example, the growth of cancer. Lastly, using the results obtained, conclusions are enumerated, inferences are outlined and directions for future studies are considered. / by Jagadeshwari Karri. / Thesis (M.S.C.S.)--Florida Atlantic University, 2012. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Lam, Man Ting. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 128-138). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Orientador: Elaine Sbroggio de Oliveira Rodini / Banca: Adriana Camargo Ferrasi / Banca: Tânia Yoshico Kamiya / Resumo: Introdução: A infertilidade é definida como a incapacidade de um casal obter uma gravidez ou parto de um bebê vivo. Ela não é exclusiva da mulher, mas sim do casal, e os fatores mais comuns associados são de origem genética, como alterações dos cromossomos, incluindo também causas hormonais, anatômicas, infecciosas, imunológicas, entre outras. A definição dos tipos de alterações cromossômicas presentes em um casal com dificuldades reprodutivas é de fundamental importância para sua vida reprodutiva. Objetivo: Verificar a importância das diferentes alterações cromossômicas na etiologia da infertilidade e discutir a indicação do cariótipo nos casos de dificuldades reprodutivas. Metodologia: Estudo retrospectivo de dados de 832 indivíduos, atendidos na Faculdade de Ciências/ UNESP, Bauru, no período de Janeiro de 2005 a Dezembro de 2012, referentes a estudos cromossômicos (cariótipo de sangue periférico e abortos espontâneos) e anamnese. Resultados: Dos 832 casos, 431 foram avaliados através dos cariótipos de sangue periférico e 514 através de seus cariótipos de abortos espontâneos; 113 foram avaliados tanto pelos cariótipos de sangue como pelos cariótipos de seus abortos. A frequência das alterações cromossômicas em sangue periférico foi de 5,6%, e de 32,5 % em abortos espontâneos. Não houve correlação estatística entre ocorrência das alterações cromossômicas, sexo, idade e número de abortos. Conclusões: Na população estudada observou-se que as alterações cromossômicas são importantes na etiologia da infertilidade. As alterações cromossômicas numéricas nos abortos são as mais frequentes; contudo, sua ocorrência pode ser maior devido a possível superestimação dos cariótipos normais pela contaminação de material materno. Para prevenção de malformações congênitas, ambos os membros do casal relacionados a problemas reprodutivos devem realizar o estudo cromossômico / Abstract: Introduction: Infertility is defined as the inability of a couple of getting pregnant or give birth to a live baby. It is not only related to women, but also to the couple, and the most common factors associated are genetic, such as chromosome abnormalities as well as hormonal, anatomical, infectious and immunological causes, among others. The definition of the types of chromosomal abnormalities present in a couple with reproductive difficulties is of fundamental importance to their reproductive life. Objective: To assess the importance of different chromosomal abnormalities in the etiology of infertility and discuss the indication of the karyotype in cases of reproductive difficulties. Methodology: Karyotypes of peripheral blood and miscarriages (Chromosomal studies) and anamnesis of 832 individuals attended at the Faculdade de Ciências/ UNESP, Bauru, from January 2005 to December 2012 were assessed retrospectively. Results: Of the 832 cases, 431 were evaluated by peripheral blood karyotypes and 514 through their karyotypes of miscarriages; 113 were evaluated both by karyotypes of both blood and abortions. The frequency of chromosomal abnormalities in peripheral blood was 5.6%, and 32.5% in spontaneous abortions. There was no statistical correlation between occurrence of chromosomal abnormalities, sex, age and number of abortions. Conclusions: Chromosomal abnormalities are important in the etiology of infertility within the population studied. The numerical chromosomal abnormalities in abortions were the most common; however, its occurrence may be higher due to possible overestimation of normal karyotypes by contamination of maternal material. Aiming the prevention of congenital malformations, both couple members presenting reproductive problems should perform a chromosome study / Mestre

Orientador: Danilo Moretti-Ferreira / Coorientador: Dennis Drayna / Banca: Ana Maria Schiefer / Banca: Maria Isabel de Souza Aranha Melaragno / Banca: Robson Francisco Carvalho / Banca: Ester Silveira Ramos / Resumo: A gagueira é uma doença comum que afeta a fluência da fala, caracterizada por repetições ou prolongamentos frequentes de sons, sílaba, palavras, ou por hesitações, ou interrupções no fluxo normal da fala. Trata-se de uma doença que tipicamente surge na infância em crianças com idade entre dois e quatro anos, com taxa de incidência estimada em torno de 5% da população. No entanto devido à elevada taxa de recuperação espontânea, estima-se uma prevalência de 1% na população em geral. Apesar do envolvimento de fatores ambientais, o fator genético é determinante para o desenvolvimento da doença. Algumas evidências que sustentam essa relação são: agregação familial, estudos com gêmeos e envolvendo adoções e, relações de consanguinidade em famílias com diversos afetados. Entretanto, trata-se de uma doença complexa na qual a identificação exata do tipo de herança é difícil de ser determinada uma vez que não seguem as leis de Mendel. Este estudo teve como principal finalidade realizar análises de ligação em 43 famílias brasileiras do Estado de São Paulo, não relacionadas, portadoras de gagueira desenvolvimental persistente a fim de identificar regiões cromossômicas com possíveis genes candidatos; Para as análises de ligação, inicialmente foi realizada a genotipagem de todas as famílias através de chips específicos para essa finalidade contendo 6056 marcadores SNP. Posteriormente, para o refinamento do mapa de ligação foram utilizados marcadores microssatélites polimórficos marcados com fluoróforos e analisados em sequenciador automático capilar. Para as estimativas das frequências alélicas destes marcadores na população brasileira foram utilizados amostras do grupo controle, não relacionadas, previamente selecionadas. Apenas duas famílias (BRPD_47 e BRPD_50) sob o padrão de herança dominante... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Stuttering is a common disease that affects the fluency of speech, and is characterized by frequent repetitions or prolongations of sounds, syllables, or words, or by interruptions in the normal flow of speech. The disorder typically begins in children aged two to four years, and has an estimated incidence rate of around 5% of the population. Due to the high rate of spontaneous recovery, the estimated prevalence of the disorder is 1% in the general population. Despite the involvement of environmental factors, genetic factors have been shown to be critical to the development of the disease. Evidence supporting genetic factors include twin studies, adoption studies, family clusters of stuttering, and consanguineous relations in families with many cases of the disorder. However stuttering is a complex disorder in which the identification of the exact type of inheritance is difficult to determine because it does not follow Mendelian laws. The main goal of this study was to perform a genome-wide linkage analysis in 43 unrelated families from the Brazilian state of São Paulo, which had multiple cases of persistent developmental stuttering, in an effort to identify chromosomal regions containing possible causal genes, Linkage analysis was initially performed by genotyping of all families with chip-based methods that assayed 6056 sNP markers. Subsequent refinement of linkage locations used polymorphic microsatellite markers analyzed by capillary electrophoresis unsing an automated DNA sequencer. Unrelated normal Brazilian samples were used as a control group to estimate the allele frequencies of these markers in this population. Two families (BRPD_47 and BRPD_50) showed significant evidence for linkage in the region of chromosome 10q21 under a dominant inheritance model. Combining these two families produced... (Complete abstract click electronic access below) / Doutor