Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (p. 156-158).

Introduction: As a part of the Gene Regulators in Disease project (GRID), this study aims to create a novel high throughput method to discover the genetic effect on gene translation, taking advantage of the rationale that efficiently translated mRNAs associate with multiple ribosomes, while less active ones with fewer or none. / Methods: Lymphoblastoid cell lines (LCLs) from 44 HapMap European individuals were used for polyribosomal fractionation and establishing the sample bank for the future study. The fractionated mRNA samples of 10 out of the 44 individuals were run on an Illumina GoldenGate Beadarray to detect allelic imbalance (developed by the group of T.J. Hudson and T.M. Pastinen). / Results: This study established a high-quality RNA bank, including 1,100 RNA fraction samples. By the Illumina chip, translational imbalance was detected in 75 out of 1483 (5.06%) assays, and 63 out of269 (23.4%) genes. The translational effect was well replicable by the resequencing method. / Conclusion: This study found that genetic effect on gene translation is a common mechanism of expression regulation. Our best hit found in the integrin beta 1 binding protein 1 gene (ITGB1BP1 ) highlights the role of mRNA 3'UTR secondary structure in gene translation. / Keywords: Gene translation, High throughput genotyping, Human genetics, Polyribosome, RNA, Single nucleotide polymorphism

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 6 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from first page of PDF file (viewed on June 23, 2009). Includes bibliographical references (p. 113-117).

Thesis (Ph. D.)--University of Washington, 2008. / Vita. Includes bibliographical references (p. 80-97).

No description available.

INTRODUÇÃO: O câncer de próstata (CaP) é a neoplasia mais comum no homem depois do câncer de pele não-melanoma. É uma doença de comportamento heterogêneo e a hereditariedade é um dos principais fatores de risco. Recentes estudos do genoma humano revelaram numerosas regiões de susceptibilidade associada com a doença. Os Polimorfismos de Nucleotídeo Único (SNPs) são variantes de risco genéticos associados com uma série de doenças incluindo o câncer. Considerando que a história familiar constitui fator de risco para o desenvolvimento do CaP, acredita-se que a identificação de polimorfismos envolvidos nesse processo possa ter um papel relevante para auxiliar no desenvolvimento de ferramentas alternativas para a detecção precoce e para a definição do prognóstico desta neoplasia. OBJETIVOS: Análise dos polimorfismos genéticos relacionados ao desenvolvimento do câncer de próstata em indivíduos com história familiar para a doença. Além disso, correlacionar a frequência dos polimorfismos e os fatores prognósticos, tais como: nível do antígeno prostático específico (PSA), escore de Gleason, estadiamento patológico e recidiva bioquímica. MÉTODOS: Neste estudo foi analisado a frequência de 20 SNPs em 255 pacientes, sendo 185 pacientes portadores de câncer de próstata e 70 grupo controle. No grupo diagnosticado com CaP, tinham 97 casos esporádicos e 72 com histórico familiar (dois parentes de primeiro grau). O grupo controle foi composto por homens sem diagnóstico de CaP que estavam em prevenção com parâmetros como psa e toque retal normais. Todos foram submetidos a extração do DNA e o genótipo avaliado através da técnica de reação em cadeia da polimerase quantitativa em tempo real. A análise estatística foi realizada comparando a genotipagem e a frequência alélica entre os grupos, utilizando o teste de qui-quadrado com valor de significância menor ou igual a 0,05. RESULTADOS: Dois dos 20 polimorfismos apresentaram associação significativa com o CaP hereditário, o SNP rs7931342 (11q13.2) onde o genótipo homozigoto foi cinco vezes mais frequente (p=0,01) e o rs10090154 (8q24) onde o alelo polimórfico aumenta duas vezes e meia a chance de CaP hereditário (OR=2,67; p=0,04). O rs2660753 (3p12.1) mostrou relevância para o CaP esporádico onde a presença do alelo polimórfico tem um efeito protetor para o desenvolvimento da doença (OR=0,50; p=0,01). Com relação a associação dos fatores prognósticos, foram encontrados achados significativos para o SNP rs620861 (8q24) onde o genótipo homozigoto selvagem está associado com menor escore de Gleason (p=0,04). O polimorfismo rs1447295 (8q24) está relacionado a um melhor prognóstico, pois foi mais frequente nos pacientes com estadiamento localizado, sem recidiva bioquímica e com sobrevida livre de recidiva mais longa. CONCLUSÃO: Nosso estudo evidenciou dois SNP (rs7931342 e rs10090154) como fator de risco para o desenvolvimento de CaP hereditário. Com relação o CaP esporádico, a presença do alelo polimórfico do rs2660753 demonstra um efeito protetor. Por último, comparando os fatores prognósticos, tanto o genótipo homozigoto selvagem do rs620861 como o homozigoto polimórfico do rs1447295 conferem um bom prognóstico / INTRODUCTION: Prostate cancer (PCa) is the most common non-cutaneous malignancy among men. It is a heterogeneous disease and heredity is one of the strongest risk factors. Recent studies of the human genome revealed numerous susceptibility regions associated with the disease. Several single nucleotide polymorphisms (SNPs) have been implicated in the risk of developing the prostate cancer. Considering that the family history is a risk factor for PCa development, we believe that identification of polymorphisms involved in these processes may have an important role to help in the development of alternative tools for early detection and to define the prognosis of this neoplasm. OBJECTIVES: Analysis of genetic polymorphisms associated with the development of prostate cancer in patients with family history of prostate cancer. Moreover, correlate the frequency of polymorphisms and prognostic factors such as PSA level, Gleason score, pathological stage and biochemical recurrence. METHODS: In this study, the frequency of 20 genetic single nucleotide polymorphisms were analyzed in 255 patients, 185 patients with prostate cancer and 70 control. In the group diagnosed with PCa, they had 97 sporadic cases and 72 had a family history (two first-degree relatives). The control group consisted of men with no diagnosis of PCa who were on prevention with parameters such as normal psa and digital rectal exam. All were subjected to DNA extraction and genotype assessed by real-time polymerase chain reaction technique. Statistical analysis was performed by comparing the genotype and allele frequency between the groups using the chi-square test with significance or equal to 0.05. RESULTS: Two of the 20 polymorphisms were significantly associated with hereditary CaP, the rs7931342 (11q13.2) that the homozygote genotype was five times more common (p=0.01) and rs10090154 (8q24) that the polymorphic allele increase two times and a half the risk of hereditary PCa (OR = 0.5; p = 0.04). The rs2660753 (3p12.1) showed association with sporadic PCa where the presence of polymorphic allele has a protective effect on the PCa development (OR = 2,67, p = 0.01). Regarding the association of prognostic factors, we found significant findings to the SNP rs620861 (8q24) that the wild homozygote genotype is associated with lower Gleason score (p = 0.04). The rs1447295 polymorphism (8q24) is related to a better prognosis because it was more frequent in patients with localized stage, without biochemical recurrence and longer recurrence-free survival. CONCLUSIONS: Our study showed two SNPs (rs7931342 and rs10090154) as a risk factor for hereditary PCa development. Regarding the sporadic PCa, the polymorphic allele presence of rs2660753 demonstrated a protective effect. Finally, comparing the prognostic factors, both wild homozygote genotype of rs620861 and polymorphic homozygote of rs1447295 offer a good prognosis

Xiang Hai Liao. / "July 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 180-200). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.