Orientadores: Louis Bernard Klaczko, Galina Ananina / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T15:35:04Z (GMT). No. of bitstreams: 1 Batista_MarcosRobertoDias_D.pdf: 1499232 bytes, checksum: f14f9f280608caee726a8954c332d6b9 (MD5) Previous issue date: 2010 / Resumo: Nesta tese, estudamos uma questão básica e uma aplicada: os determinantes da variação geográfica e temporal do polimorfismo de inversões do segundo cromossomo em populações naturais de Drosophila mediopunctata; ainda, adaptamos a técnica para análise de politênicos de Drosophila para estudos em Cochliomyia hominivorax e assim elaboramos um mapa dos cromossomos politênicos desta praga da pecuária. Duas décadas depois de estudos anteriores, realizamos cinco novas coletas no Itatiaia e observamos inesperadas mudanças nas frequências dos arranjos mais comuns e em sua variação microgeográfica em relação àquelas antes descritas. No segundo cromossomo, o arranjo DA continua sendo o mais frequente, porém não detectamos mais uma correlação significativa com a altitude. Para os arranjos DS e DP, além de não haver mais correlações significativas com a altitude, suas frequências se mostram ainda mais baixas, principalmente no inverno. Entretanto, o ciclo sazonal observado para estas inversões se mantém. O arranjo DI aumentou sua frequência significativamente e agora mostra uma correlação positiva e significativa com a altitude. Estes resultados sugerem que, depois de duas décadas, houve mudanças ambientais incluindo alterações climáticas e provavelmente fatores bióticos que devem ter afetado a arquitetura genética das populações. Observamos uma diferenciação entre o padrão das frequências de inversões do cromossomo II de populações vizinhas de D. mediopunctata. As matas estudadas estão situadas em duas diferentes unidades geomorfológicas, que apresentam diferenças marcantes em relação ao solo, relevo, paisagem, vegetação e fauna. Nossos resultados sugerem que a diferenciação geográfica observada nas frequências de inversões pode ser resultado de uma adaptação local às diferenças florísticas e climáticas. Entretanto, outros marcadores genéticos devem ser pesquisados para analisar os efeitos da fragmentação florestal sobre as populações. Cochliomyia hominivorax, conhecida no Brasil como a mosca-da-bicheira, é considerada uma das principais moscas causadoras de miíases primária na região Neotropical. Apesar de um fotomapa preliminar de seus cromossomos politênicos ter sido publicado anteriormente, com resultados encorajadores, não havia um mapa dos cromossomos politênicos com boa resolução para a espécie. Desta forma, elaboramos um novo fotomapa dos cinco autossomos com uma resolução total de 1450 bandas / Abstract: In this thesis, we studied a basic and an applied issue: the determinants of geographical and temporal variation of the second chromosome inversion polymorphism in natural populations of Drosophila mediopunctata; and, adapting the squashing technique used for Drosophila to Cochliomyia hominivorax, we made a map of the polytene autosomes of this livestock pest. Two decades after previous studies, we carried out five collections in Itatiaia, RJ. We observed unexpected changes in the frequencies of the most common inversions of the second chromosome. The DA gene arrangement is still the most common, but we no longer detect a significant correlation between its frequency and altitude. Furthermore, the frequencies of DS and DP inversions became even lower, especially in winter; and didn't show a significant correlation with altitude. However, the previously observed seasonal cycle for these inversions is still present. DI frequency increased significantly, and it is now significantly positively correlated with altitude. These results suggest that, after two decades, there were modifications in the climate, but other variables - such as biotic factors -have also probably changed and may be correlated with the changes in the genetic architecture of the Itatiaia population. Furthermore, we report a differentiation between frequencies of inversions of the second chromosome in neighboring populations of D. mediopunctata. The forests studied are located over two geomorphologic units that have marked differences regarding landscape, topography, soil, vegetation, and fauna. Our results suggest that the observed geographical variation in the inversion frequencies may be a result of local adaptation to climate and floral and faunal changes. However, further analysis with other genetic markers must be performed to assess the possible effects of forest fragmentation on different populations. Cochliomyia hominivorax, the New World screwworm fly is one of the main flies causing primary myiasis in the Neotropical region. Although a preliminary photomap of the polytene chromosomes of C. hominivorax was previously published, a good resolution map of the polytene chromosomes was not available for this species. Here, we present a new photomap of the five autosomes of this species with a total resolution of 1450 bands / Doutorado / Genetica Animal e Evolução / Doutor em Genetica e Biologia Molecular

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: With knowledge of the human genome increasing constantly we are continually faced with new and potentially groundbreaking methods for managing, treating and/or identifying diseases and predisposition to diseases and conditions at a genetic level. The human cytochrome P450 (CYP) super-family of genes code for enzymes that can participate in metabolism of drugs and foreign chemicals and in steroid synthesis and metabolism. Mutations in these genes may contribute to clinically relevant diseases. In this study, the effects of mutations within four CYP genes were evaluated in two South African disease groups - variegate porphyria and breast cancer. Variegate porphyria (VP) has an unusually high incidence in South Africa due to the R59W founder mutation in the protoporphyrinogen oxidase (PPOX) gene that causes a disruption in the haem biosynthetic pathway. VP presents with variable clinical symptoms and has a relatively low penetrance. It is expected that environmental factors and modifier genes play a role in the clinical expression of VP. CYP genes are implicated as candidate modifier genes for the expression of VP due to the function they have in metabolising many drugs contraindicated in porphyria patients, and the necessity of haem binding to the apoprotein to produce a functional CYP enzyme. This is the first study to investigate CYPs as possible modifier genes for VP clinical expression. Six CYP polymorphisms (CYPIAlml, CYPIAlm2, CYPIA2 - 734 C>A, CYPIBI 8372 A>C, CYP2D6*3, CYP2D6*4), associated with four CYP loci, were genotyped in a VP population and a suitable control population. The results observed are suggestive of CYPIAlml and CYPIBI playing a role as modifiers for the clinical expression of VP as they were significantly associated (P<O.05) with the presence ofVP related symptoms. Breast cancer is one of the leading causes of death in women due to cancer. It is believed that breast cancer may be the result of co-participation between common DNA alterations and environmental exposures. Polymorphisms in enzymes involved with the metabolism of environmental exposures, such as the cytochrome P450 enzymes, are therefore expected to play an aetiological role in breast cancer. Two groups of South African breast cancer patients (Caucasian and of mixed ancestry) and population-matched controls were genotyped for four CYP polymorphisms (CYPIAlml, CYPIAlm2, CYPIA2 -734 C>A and CYPIBI 8372 A>C). This represents the first investigation of the potential role of CYPs as breast cancer risk modifiers in the two South African populations. Significant differences were observed (P<O.003) in genotype and allele frequencies between the breast cancer patients and controls for the CYPIBI 8372 A>C polymorphism in the population of mixed ancestry. Vast differences in allele frequencies were also observed between the two groups of breast cancer populations. These results emphasize the importance of population-based risk assessment when genetic testing and counselling for complex disease susceptibility is offered. The results of this study provide the first evidence suggesting a role for CYPs in modifying the clinical expression of VP and in acting as risk factors for developing breast cancer in a South African population. / AFRIKAANSE OPSOMMING: Met die konstante toename van kennis oor die mensgenoom kom ons voortdurend te staan voor nuwe metodes vir die beheer, behandeling en/of identifikasie van siektes en vatbaarheid vir siektes op 'n genetiese vlak. Die mens sitochroom P450 geensuperfamilie kodeer vir ensieme betrokke in die metabolisme van medisyne en ander chemiese stowwe en steroïed-sintese en -metabolisme. Mutasies in hierdie gene kan 'n bydrae lewer tot kliniese relevante siektes. In hierdie studie is die effek van mutasies in vier sitochroom gene bestudeer in twee Suid-Afrikaanse siekte groepe, variegate porfirie en borskanker. Variegate porfirie (VP) het 'n besonderse hoë frekwensie in Suid-Afrika as gevolg van die R59W stigter-mutasie in die protoporfirinogeen oksidase (PPOX) geen. Hierdie mutasie lei tot 'n versteuring in die heem biosintese padweg. VP presenteer met variërende kliniese simptome en het 'n betreklike lae penetrasie. Daar word vermoed dat omgewingsfaktore en kandidaat modifiserende gene 'n rol speel in die kliniese beeld van VP. Sitochroom P450 gene is geïdentifiseer as kandidaat modifiserende gene as gevolg van hulle rol in die metabolisme van verbode medikasie vir porfirie pasiënte, asook die binding van heem aan die apoproteïen wat noodsaaklik is vir die produksie van funksionele sitochroom P450 ensiem. Hierdie is die eerste studie wat sitochroom P450 gene as moontlike modifiserende gene vir die kliniese uitdrukking van VP ondersoek. Ses sitochroom P450 polimorfismes (CYPIAlml, CYPIAlm2, CYPIA2 -734 C>A, CYPIBI 8372 A>C, CYP2D6*3, CYP2D6*4) is ondersoek in beide 'n VP populasie en 'n geskikte kontrole populasie. Die resultate suggereer 'n rol vir CYPIAlml en CYPIBI in die modifisering van die kliniese uitdrukking van VP aangesien hulle betekenisvolle assosiasie (P<O.05) met die voorkoms van VP-verwante simptome getoon het. Borskanker IS een van die vernaamste oorsake van kankersterftes onder vroue. Borskanker IS waarskynlik die resultaat van interaksie tussen algemene DNSveranderinge en omgewings-blootstelling. Daar word dus verwag dat polimorfismes in ensieme betrokke by die metabolisme van omgewingselemente, soos byvoorbeeld die sitochroom P450 ensieme, 'n etiolgiese rol in borskanker sal speel. Die genotipes van twee groepe Suid-Afrikaanse borskanker lyers (Kaukasiërs en van gemengde herkoms) en populasie-passende kontroles is bepaal vir vier sitochroom P450 polimorfismes (CYPIAlml, CYPIAlm2, CYPIA2 -734 C>A, CYPIBI 8372 A>C). Hierdie studie verteenwordig die eerste ondersoek na die potensiële rol van sitochroom P450s as risiko-modifiserende faktore vir borskanker in die twee populasies. Betekenisvolle verskille (P<O.003) in genotipe en allele frekwensies is waargeneem tussen die borskanker lyers en kontroles vir die CYPIBI 8372 A>C polimorfisme in die gemengde herkoms populasie. Beduidende verskille in alleel frekwensies is ook waargeneem tussen die twee borskanker populasies. Hierdie resultate beklemtoon die belangrikheid van populasie gebaseerde risiko-beraming wanneer genetiese toetse en voorligting vir komplekse siekte-vatbaarheid aangebied word. Die resultate van hierdie studie bied die eerste getuienis dat sitochroom P450s 'n rol kan speel in die modifisering van die kliniese beeld van VP en ook kan optree as as risiko faktore vir die ontwikkeling van borskanker in 'n Suid-Afrikaanse populasie.

Thesis (M.S.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / Source: Masters Abstracts International, Volume: 46-01, page: 0238. Adviser: Marsha Frazier. Includes bibliographical references.

Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5301. Adviser: Eric Boerwinkle. Includes bibliographical references.

Orientador: Ana Silvia Alves Meira Tavares Moura / Banca: Luiz Lehmann Coutinho / Banca: Mônica Corrêa Ledur / Banca: Millor Fernandes do Rosário / Banca: José Roberto Sartori / Resumo: A partir de resultados de um estudo anterior, no qual foram mapeados QTLs para características de peso vivo, peso do coração e pulmões no GGA1, foi definida uma região no intervalo entre os marcadores ADL0234 e LEI0071, abrangendo 82,3 cM. Foram avaliadas três famílias de meios-irmãos paternos que compreendiam sete famílias de irmãos completos, num total de 652 F2 para as características: peso vivo aos 35 e 41 dias de idade, pesos do coração e pulmões e rendimentos de coração e pulmões. Os genótipos de seis marcadores microssatélites foram adicionados aos dez utilizados anteriormente. O mapa de ligação obtido da região compreendeu 110,8 cM com espaçamento médio entre os marcadores de 7,4 cM. Na análise de F2, em um único intervalo (LEI0146-LEI0174), compreendendo 28,8 cM, foram mapeados QTLs para todas as características estudadas, com exceção dos rendimentos de coração e pulmões. Neste intervalo estão localizados o gene IGF1 e o centrômero do cromossomo. A adição de seis marcadores confirmou os QTLs mapeados anteriormente, porém alguns em diferentes posições. A análise de meios-irmãos paternos indicou que os principais QTLs estavam segregando em apenas uma das famílias (7716), na qual cinco QTLs foram mapeados. Na análise de meios-irmãos maternos, duas famílias segregaram QTLs tanto na análise Individual como na Conjunta (7810 e 7971). As diferentes análises permitiram selecionar dois casais F1, que devem ser o alvo dos próximos estudos. Este estudo restringiu a busca por genes candidatos responsáveis pelas características de interesse a uma região de 28,8 cM (9,82 Mb) no GGA1. / Abstract: Based on the results from a previous study, in which QTL for body weight, heart and lungs weights and heart and lungs percentages were mapped to GGA1, a region was defined between markers ADL0234 and LEI0071, spanning 82.3 cM. Three paternal half-sib families, comprising seven full-sib families, totaling 652 F2 were evaluated for body weight at 35 and 41 days of age, heart and lungs weights and heart and lungs yields. Genotypes of six microsatellite markers were added to those of ten previously used. The linkage map of this region spanned 110.8 cM, with average spacing of 7.4 cM between markers. In a single interval (LEI0146-LEI0174), comprising 28.8 cM, QTLs for all traits, except for heart and lungs yields were mapped in the F2 analysis. In this same interval the IGF1 gene, and the chromosome centromere, are located. The use of six additional markers confirmed the same QTLs mapped previously, but some of them, in different positions. The paternal half-sib analysis indicated that the main QTLs were segregating in one of the families only (7716), in which five QTLs were mapped. In the maternal half-sib analysis, two families segregated QTLs both, in the across and within families analyses (7810 and 7971). These analyses allowed the selection of two F1 couples to be the target for future studies. This study restricted the search for candidate genes responsible for the traits of interest to a region of 28.8 cM (9.82 Mb) in GGA1. / Doutor

Made available in DSpace on 2015-03-26T13:42:21Z (GMT). No. of bitstreams: 1 texto completo.pdf: 3749391 bytes, checksum: 3aaf46231fff9be22a66ac420fb3e525 (MD5) Previous issue date: 2011-02-14 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / A complexa família Characidae é parte da fauna ictiológica neotropical e conta com várias espécies e gêneros em condição de Incertae Sedis. Os gêneros Astyanax e Oligosarcus, considerados muito aparentados, estão incluídos nesta família e abrangem espécies de pequeno tamanho e expressiva abundância em muitos rios e córregos da América do sul. Na bacia do rio Doce, no sudeste brasileiro, uma análise morfológica preliminar permitiu a identificação de cinco peixes &#8220;semelhantes à Astyanax&#8221; que continham no seu osso maxilar de 8 a 13 dentes. Esses cinco peixes, chamados no presente trabalho de dentuços, foram coletados em simpatria com as espécies Astyanax bimaculatus (Linneaus, 1758), Astyanax giton (Eigenmann, 1908) e Oligosarcus argenteus Günther, 1864. De modo a determinar a natureza biológica dos dentuços, foi realizado um estudo multidisciplinar envolvendo dados morfológicos citogenéticos e moleculares. Os dentuços apresentaram configurações intermediárias entre as espécies A. giton e O. argenteus no que diz respeito ao número de escamas na linha lateral e ao número de dentes no osso maxilar. As análises citogenéticas, feitas através das técnicas de Giemsa, bandeamento NOR, bandeamento-C, fluorocromos, e FISH, indicaram que todas as espécies de caracídeos contaram com número diploide 2n=50 cromossomos diferindo, porém, em vários caracteres de sua morfologia cromossômica. Os dentuços caracterizaram-se por apresentar altos índices de variação cromossômica tanto intra- como inter-individual. Além do mais, eles contaram com vários cromossomos não pareáveis assim como cromossomos de tamanho diminuto que não são observados em nenhuma daquelas espécies simpátricas de Characidae. Três espécimes dos dentuços apresentaram seu fragmento de DNA do gene mitocondrial citocromo b (475 pb) idêntico aquele de O. argenteus e, contudo, todos os dentuços compartilhavam mais alelos ISSR com os espécimes de A. giton do que com os espécimes de O. argenteus. Por outro lado, uma espécie de dentuço conta com o gene cyt. b idêntico aquele das espécies de A. giton estudadas. A análise de fragmentos ITS-1 (1123 pb) mostrou que os dentuços têm sequencias mais relacionadas à Oligosarcus argenteus. Os dados, desse modo, sugeriram que os dentuços são híbridos entre as espécies A. giton e O. argenteus representando assim o primeiro caso de hibridismo espontâneo entre dois gêneros de peixes neotropicais. A relevância de tal descoberta para a biologia da conservação e para as investigações filogenéticas foram discutidas. / Within the Neotropical fish fauna, the taxonomically complex family Characidae has many species and genera in Incertae Sedis condition. Within this family, the closely related genera Astyanax and Oligosarcus are represented by small sized fishes that are an expressive proportion of the freshwater biodiversity in many rivers of South America. In the Doce River Basin, Southeastern Brazil, a preliminary morphologic analysis indicated the presence of 5 Astyanax-like fish with unusually high numbers (8-13) of maxillary teeth which are referred as &#8220;toothed morphs&#8221;. These fishes were collected in sympatry with Astyanax bimaculatus (Linneaus, 1758), Astyanax giton (Eigenmann, 1908), and Oligosarcus argenteus Günther, 1864. To determine the biological status of them a comparative multidisciplinary approach involving morphologic, cytogenetic and molecular data was conducted, with the toothed morphs and their sympatric species. The toothed morphs showed an intermediate position in lateral line scale numbers and maxillary teeth number between A. giton and O. argenteus. Cytogenetic analyses (Giemsa, NOR, C-banding, fluorochromes and FISH) indicated that all sympatric characids were 2n=50, although they differed from each other in many other karyotypic characters. The toothed morphs were characterized by high levels of intra and inter-individual chromosomal variation including several unpairable chromosomes and tiny chromosomes that were not observed in either of the other sympatric species. Three toothed morphs specimens had their cytochrome b DNA fragment (475 bp) identical to O. argenteus, with one exception which its cyt. b DNA sequence was identical to A. giton. Moreover, all toothed morphs ITS-1 DNA sequences were characterized by their similitude to those sequences of Oligosarcus argenteus. On the other hand, all toothed morphs shared more ISSR alleles with A. giton. The data suggested that the toothed morphs were hybrids between A. giton and O. argenteus, representing the first evidence for spontaneous hybridization between two Neotropical fish genera. The relevance of such findings in conservation biology and phylogeny assessment were discussed.

Zhang, Ji. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 100-104). / Abstracts in English and Chinese. / Chapter CHAPTER 1. --- Introduction / Chapter 1.1. --- Introduction of genetic association studies --- p.1 / Chapter 1.1.1. --- Application of genetic association studies in complex diseases --- p.3 / Chapter 1.1.2. --- Application of genetic association studies in type-2 diabetes --- p.4 / Chapter 1.2. --- Study design of genetic association studies --- p.7 / Chapter 1.3. --- Overview of statistical approaches in association studies --- p.10 / Chapter 1.3.1. --- Preliminary analyses --- p.10 / Chapter 1.3.1.1. --- HardýؤWeinberg equilibrium testing --- p.10 / Chapter 1.3.1.2. --- Inference of missing genotype data --- p.12 / Chapter 1.3.1.3. --- SNP tagging --- p.14 / Chapter 1.3.2. --- Single-point and multipoint tests for association --- p.15 / Chapter 1.4. --- Other relevant methods employed in this study --- p.20 / Chapter 1.4.1. --- Self-Organizing Maps (SOM) with further classification by K-means clustering --- p.20 / Chapter 1.4.2. --- Random forests --- p.27 / Chapter 1.5. --- Main objectives of this study --- p.31 / Chapter CHAPTER 2. --- Materials and methods / Chapter 2.1. --- Study cohort --- p.32 / Chapter 2.2. --- Study design --- p.34 / Chapter 2.2.1. --- Construction of sample sets for each stage using SOM and K-means clustering --- p.34 / Chapter 2.2.2. --- Stage 1 analysis by random forests --- p.37 / Chapter 2.2.3. --- Stage 2 analysis by chi-square test --- p.42 / Chapter 2.2.4. --- Two-stage genetic association study by chi-square test --- p.43 / Chapter 2.2.5. --- Comparison of results: random forests plus chi-square test versus chi-square test --- p.43 / Chapter 2.2.6. --- Validation of results in the whole sample set by allelic chi-square test --- p.44 / Chapter 2.2.7. --- Extensions of the study: cumulative effects of candidate SNPs on risk of type-2 diabetes --- p.45 / Chapter CHAPTER 3. --- Results / Chapter 3.1. --- Effects of sample classification by SOM and K-means clustering --- p.50 / Chapter 3.2. --- Genetic associations in stage 1 --- p.64 / Chapter 3.3. --- Genetic associations in stage 2 and validation of results --- p.69 / Chapter 3.4. --- Cumulative effects of candidate SNPs on risk of type-2 diabetes --- p.76 / Chapter CHAPTER 4. --- Discussion / Chapter 4.1. --- Overall strategy --- p.81 / Chapter 4.1.1. --- Effects of SOM and K-means clustering --- p.82 / Chapter 4.1.2. --- Effects of random forests in the first stage of association study --- p.83 / Chapter 4.1.3. --- Comparison of our method with traditional chi-square test --- p.84 / Chapter 4.1.4. --- Joint effects of candidate SNPs selected by the hybrid method --- p.86 / Chapter 4.2. --- Biological significance of candidate SNPs --- p.88 / Chapter 4.2.1. --- Gene CDKAL1 --- p.89 / Chapter 4.2.2. --- Gene KIAA1305 --- p.90 / Chapter 4.2.3. --- Gene DACH1 --- p.91 / Chapter 4.2.4. --- Gene FUCA1 --- p.92 / Chapter 4.2.5. --- Gene KCNQ1 --- p.93 / Chapter 4.2.6. --- Gene SLC27A1 --- p.94 / Chapter 4.3. --- Limits and improvement of this study --- p.96 / Chapter 4.4. --- Conclusion --- p.99 / REFERENCES --- p.100

Ching, Ka Wai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves [69-80]). / Abstract also in Chinese. / Abstract (in English) --- p.ii / Abstract (in Chinese) --- p.v / Acknowledgement --- p.viii / Table of Contents --- p.ix / List of Tables --- p.xii / List of Figures --- p.xiii / Glossary of Terms and Abbreviations --- p.xv / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1 --- Introduction of Atopic Eczema (AE) --- p.1 / Chapter 1.1.1 --- Definition and classification of AE --- p.1 / Chapter 1.1.2 --- Epidemiology --- p.3 / Chapter 1.1.2.1 --- The hygiene hypothesis --- p.5 / Chapter 1.2 --- Pathogenesis and Etiology --- p.6 / Chapter 1.2.1 --- Biphasic type-1/type-2 T-helper lymphocyte (Thl/Th2) immunological responses --- p.6 / Chapter 1.2.2 --- Nature and involvements of immunoglobin E (IgE) --- p.8 / Chapter 1.2.3 --- Microbial colonization --- p.9 / Chapter 1.2.4 --- Cytokines involvement --- p.10 / Chapter 1.2.5 --- Pruritus inducing neurotrophic factors --- p.11 / Chapter 1.2.6 --- "Food allergens, aeroallergens" --- p.12 / Chapter 1.2.7 --- Dysregulation of innate immune system --- p.13 / Chapter 1.2.7.1 --- Dysregulation of antimicrobial peptides --- p.14 / Chapter 1.2.7.2 --- Skin barrier impairment --- p.14 / Chapter 1.2.8 --- Genetic predisposition --- p.15 / Chapter 1.3 --- Assessments of Atopic Eczema (AE) --- p.17 / Chapter 1.3.1 --- AE severity assessment --- p.17 / Chapter 1.3.1.1 --- Scoring of atopic dermatitis (SCORAD) system --- p.17 / Chapter 1.3.1.2 --- Nottingham eczema severity score (NESS) --- p.20 / Chapter 1.3.2 --- Dermatological parameter - skin hydration (SH) and transepidermal water loss (TEWL) --- p.22 / Chapter 1.4 --- Chitinase (CHIA) --- p.22 / Chapter 1.4.1 --- Chitin and CHIA --- p.22 / Chapter 1.4.2 --- Association of acid mammalian chitinase (AMCase) with asthma --- p.23 / Chapter 1.4.3 --- Hygiene hypothesis implies: AMCase and allergy relationship --- p.24 / Chapter Chapter 2: --- Hypothesis and Objectives --- p.25 / Chapter 2.1 --- Hypothesis - based on CHIA involvements in canine AE --- p.25 / Chapter 2.2 --- Hypothesis --- p.25 / Chapter 2.3 --- Objective 226}0ؤ based on AMCase single nucleotide polymorphism (SNPs) in asthma susceptibility --- p.25 / Chapter 2.4 --- Objectives --- p.27 / Chapter Chapter 3: --- Methodology --- p.28 / Chapter 3.1 --- Recruitment of cases and controls --- p.28 / Chapter 3.2 --- Assessment of clinical parameters --- p.29 / Chapter 3.2.1 --- Scoring of atopic dermatitis (SCORAD) system --- p.29 / Chapter 3.2.2 --- Nottingham eczema severity score (NESS) --- p.29 / Chapter 3.2.3 --- Dermatologic parameters --- p.29 / Chapter 3.2.3.1 --- Cutaneous bacterial colonization --- p.29 / Chapter 3.2.3.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.30 / Chapter 3.3 --- Peripheral blood collection and genomic deoxyribonucleic acid (DNA) extraction --- p.30 / Chapter 3.4 --- Acid mammalian chitinase (AMCase) polymorphism genotyping --- p.31 / Chapter 3.4.1 --- Polymerase chain reactions (PCR) amplification of AMCase gene --- p.31 / Chapter 3.4.1.1 --- List of PCR reagents --- p.32 / Chapter 3.4.1.2 --- Electrophoresis reagents --- p.33 / Chapter 3.4.2 --- Restriction fragment length polymorphism (RFLP) analysis of AMCase and confirmation with direct sequencing --- p.33 / Chapter 3.5 --- Statistical analysis --- p.34 / Chapter Chapter 4: --- Results and Data Analysis --- p.36 / Chapter 4.1 --- Results --- p.36 / Chapter 4.1.1 --- Demographic data of cases and controls --- p.36 / Chapter 4.1.2 --- PCR amplification and RFLP analysis of AMCase gene --- p.37 / Chapter 4.1.3 --- PCR cycle sequencing of the PCR fragments --- p.40 / Chapter 4.2 --- Data analysis --- p.41 / Chapter 4.2.1 --- Data overview --- p.41 / Chapter 4.2.2 --- Genotypes distribution of AMCase polymorphisms --- p.43 / Chapter 4.2.2.1 --- Allele frequency comparison of AMCase single nucleotide polymorphism (SNPs) by chi-square --- p.43 / Chapter 4.2.2.2 --- Allele frequency comparison of AMCase SNPs by logistic regression analysis --- p.44 / Chapter 4.2.3 --- Haplotype frequency estimation via maximum likelihood algorithm --- p.45 / Chapter 4.2.4 --- Association of AMCase polymorphism with Atopic Eczema (AE) clinical parameters --- p.47 / Chapter 4.2.4.1 --- Peripheral blood eosinophil counts --- p.48 / Chapter 4.2.4.2 --- Serum immunoglobin E (IgE) level --- p.49 / Chapter 4.2.4.3 --- Dermatologic factors --- p.49 / Chapter 4.2.4.3.1 --- Cutaneous Staphylococcus aureus colonization --- p.49 / Chapter 4.2.4.3.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.50 / Chapter Chapter 5: --- Discussion --- p.52 / Chapter 5.1 --- Data overview --- p.52 / Chapter 5.2 --- AMCase rs3806448 polymorphism was significantly different among AE cases and controls --- p.53 / Chapter 5.2.1 --- Allele frequency comparison of AMCase SNPs polymorphisms by chi-square --- p.53 / Chapter 5.2.2 --- Allele frequency comparison of AMCase SNPs polymorphisms by logistic regression analysis --- p.54 / Chapter 5.2.3 --- The possible genetic modification by rs3806448 homozygous recessive genotype --- p.55 / Chapter 5.3 --- "Significant difference of haplotype frequency, 2212 among case-control comparison" --- p.56 / Chapter 5.4 --- Strong associations between AMCase SNPs polymorphisms and clinical parameters of AE --- p.57 / Chapter 5.4.1 --- Peripheral blood eosinophil counts --- p.57 / Chapter 5.4.2 --- Dermatologic factors --- p.58 / Chapter 5.4.2.1 --- Cutaneous Staphylococcus aureus colonization --- p.58 / Chapter 5.4.2.2 --- Skin hydration (SH) and transepidermal water loss (TEWL) --- p.59 / Chapter 5.5 --- Limitation of the present study --- p.59 / Chapter Chapter 6: --- Conclusion and Future Prospect --- p.62 / Chapter 6.1 --- Conclusion --- p.62 / Chapter 6.2 --- Future prospect --- p.62 / Chapter Chapter 7: --- Appendices --- p.64 / Chapter Chapter 8: --- References --- p.69

Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

Liu, Zhi Kai. / Thesis submitted in: December 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 105-117). / Abstracts in English and Chinese. / Abstract (English version) --- p.i / Abstract (Chinese version) --- p.v / Acknowledgement --- p.vii / Statement of contribution --- p.x / Table of Contents --- p.xi / List of Tables --- p.xv / List of Figures --- p.xviii / List of Abbreviations --- p.xix / Publications arising from this thesis --- p.xxi / Chapter Chapter One --- Introduction / Chapter 1.1 --- "Lipids, lipoproteins and lipid metabolism" --- p.1 / Chapter 1.1.1 --- Cholesterol --- p.1 / Chapter 1.1.2 --- Triglycerides --- p.2 / Chapter 1.1.3 --- Lipoproteins and their metabolic pathways --- p.3 / Chapter 1.2 --- Familial combined hyerlipidemia and combined hyperlipidemia --- p.4 / Chapter 1.3 --- Single nucleotide polymorphisms --- p.9 / Chapter 1.3.1 --- SNP genotyping methods --- p.9 / Chapter 1.3.2 --- Association of SNPs with genetic diseases --- p.10 / Chapter 1.4 --- Genetic analysis of FCH and CH --- p.10 / Chapter 1.4.1 --- FCH genome scans --- p.11 / Chapter 1.4.2 --- SNP based candidate gene analysis --- p.11 / Chapter 1.5 --- Candidate genes and SNPs associated with FCH and CH --- p.12 / Chapter 1.5.1 --- Apolipoprotein A1/C3/A4/A5 gene cluster --- p.12 / Chapter 1.5.1.1 --- Apolipoprotein A1 gene --- p.15 / Chapter 1.5.1.2 --- Apolipoprotein C3 gene --- p.16 / Chapter ].5.1.3 --- Apolipoprotein A4 gene --- p.17 / Chapter 1.5.1.4 --- Apolipoprotein A5 gene --- p.18 / Chapter 1.5.2 --- Upstream transcription factor 1 gene --- p.24 / Chapter 1.5.3 --- Lipoprotein lipase gene --- p.25 / Chapter 1.5.4 --- Peroxisome proliferators-activated receptor γ gene --- p.26 / Chapter 1.5.5 --- a-adducin gene --- p.27 / Chapter 1.5.6 --- SNPs selected from the haplotype map --- p.27 / Chapter 1.6 --- Objectives --- p.28 / Chapter Chapter Two --- Materials and methods / Chapter 2.1 --- Overview --- p.31 / Chapter 2.2 --- Routine assessments --- p.32 / Chapter 2.2.1 --- Genetic hyperlipidemia survey --- p.32 / Chapter 2.2.2 --- Physical examinations --- p.33 / Chapter 2.2.3 --- Biochemical measurements --- p.33 / Chapter 2.2.3.1 --- Fasting plasma cholesterol --- p.33 / Chapter 2.2.3.2 --- Fasting plasma triglyceride --- p.34 / Chapter 2.2.3.3 --- Fasting plasma glucose --- p.34 / Chapter 2.3 --- Subjects --- p.34 / Chapter 2.3.1 --- FCH cases --- p.34 / Chapter 2.3.2 --- CH cases --- p.35 / Chapter 2.3.3 --- Normal controls --- p.36 / Chapter 2.4 --- DNA extraction from blood specimens --- p.36 / Chapter 2.4.1 --- Phenol chloroform method --- p.36 / Chapter 2.4.2 --- High pure PCR template preparation kit (Roche) --- p.37 / Chapter 2.5 --- Genotyping by the MassARRAY system --- p.38 / Chapter 2.6 --- Statistical analyses --- p.40 / Chapter 2.6.1 --- Overview --- p.40 / Chapter 2.6.2 --- Student's t-test --- p.41 / Chapter 2.6.3 --- Pearson's Chi-square test --- p.41 / Chapter 2.6.4 --- Hardy-Weinberg equilibrium --- p.41 / Chapter 2.6.5 --- Binary logistic regression test --- p.42 / Chapter 2.6.6 --- Analysis of covariance --- p.43 / Chapter 2.6.7 --- Haplotype analysis --- p.43 / Chapter 2.6.8 --- Bonferroni's correction --- p.44 / Chapter Chapter Three --- Results / Chapter 3.1 --- Overview --- p.46 / Chapter 3.2 --- Characteristics of the study population --- p.47 / Chapter 3.2.1 --- FCH cases versus controls --- p.47 / Chapter 3.2.2 --- CH cases versus controls --- p.50 / Chapter 3.3 --- Hardy-Weinberg equilibrium --- p.52 / Chapter 3.3.1 --- FCH cases and controls --- p.52 / Chapter 3.3.2 --- CH cases and controls --- p.53 / Chapter 3.4 --- APOA1/C3/A4/A5 gene cluster --- p.56 / Chapter 3.4.1 --- FCH cases versus controls --- p.56 / Chapter 3.4.1.1 --- Genotypic distribution and allelic frequency --- p.56 / Chapter 3.4.1.2 --- Odds ratio --- p.59 / Chapter 3.4.1.3 --- Parameter analysis --- p.61 / Chapter 3.4.1.4 --- Haplotype analysis --- p.68 / Chapter 3.4.2 --- CH cases versus controls --- p.69 / Chapter 3.4.2.1 --- Genotypic distribution and allelic frequency --- p.69 / Chapter 3.4.2.2 --- Odds ratio --- p.70 / Chapter 3.4.2.3 --- Parameter analysis --- p.74 / Chapter 3.4.2.4 --- Haplotype analysis --- p.83 / Chapter 3.5 --- USF1 gene --- p.84 / Chapter 3.5.1 --- FCH cases versus controls --- p.84 / Chapter 3.5.2 --- CH cases versus controls --- p.85 / Chapter 3.6 --- LPL gene --- p.87 / Chapter 3.6.1 --- FCH cases versus controls --- p.87 / Chapter 3.6.2 --- CH cases versus controls --- p.88 / Chapter 3.7 --- PPARγgene --- p.89 / Chapter 3.7.1 --- FCH cases versus controls --- p.89 / Chapter 3.7.2 --- CH cases versus controls --- p.90 / Chapter 3.8 --- ADD] gene --- p.91 / Chapter 3.8.1 --- FCH cases versus controls --- p.91 / Chapter 3.8.2 --- CH cases versus controls --- p.91 / Chapter Chapter Four --- Discussion / Chapter 4.1 --- Comparisons of the findings with these of other studies --- p.93 / Chapter 4.1.1 --- APOA1/C3/A4/A5 gene cluster --- p.93 / Chapter 4.1.1.1 --- APOA1 --- p.93 / Chapter 4.1.1.2 --- APOC3 --- p.94 / Chapter 4.1.1.3 --- APOA4 --- p.96 / Chapter 4.1.1.4 --- APOA4-A5 --- p.96 / Chapter 4.1.1.5 --- APOA5 --- p.97 / Chapter 4.1.2 --- USF1 --- p.101 / Chapter 4.1.3 --- LPL --- p.102 / Chapter 4.1.4 --- PPARγ --- p.102 / Chapter 4.1.5 --- ADD1 --- p.03 / Chapter 4.2 --- Conclusions --- p.103 / Chapter 4.3 --- Implications for future research --- p.104 / References --- p.105