Rozprawy doktorskie: „Heart – Diseases – Genetic aspects”

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McCaskie, Pamela Ann. "Multiple-imputation approaches to haplotypic analysis of population-based data with applications to cardiovascular disease". University of Western Australia. School of Population Health, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0160.

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[Truncated abstract] This thesis investigates novel methods for the genetic association analysis of haplotype data in samples of unrelated individuals, and applies these methods to the analysis of coronary heart disease and related phenotypes. Determining the inheritance pattern of genetic variants in studies of unrelated individuals can be problematic because family members of the studied individuals are often not available. For the analysis of individual genetic loci, no problem arises because the unit of interest is the observed genotype. When the unit of interest is the linear combination of alleles along one chromosome, inherited together in a haplotype, it is not always possible to determine with certainty the inheritance pattern, and therefore statistical methods to infer these patterns must be adopted. Due to genotypic heterozygosity, mutliple possible haplotype configurations can often resolve an individual's genotype measures at multiple loci. When haplotypes are not known, but are inferred statistically, an element of uncertainty is thus inherent which, if not dealt with appropriately, can result in unreliable estimates of effect sizes in an association setting. The core aim of the research described in this thesis was to develop and implement a general method for haplotype-based association analysis using multiple imputation to appropriately deal with uncertainty haplotype assignment. Regression-based approaches to association analysis provide flexible methods to investigate the influence of a covariate on a response variable, adjusting for the effects of other variables including interaction terms. ... These methods are then applied to models accommodating binary, quantitative, longitudinal and survival data. The performance of the multiple imputation method implemented was assessed using simulated data under a range of haplotypic effect sizes and genetic inheritance patterns. The multiple imputation approach performed better, on average, than ignoring haplotypic uncertainty, and provided estimates that in most cases were similar to those observed when haplotypes were known. The haplotype association methods developed in this thesis were used to investigate the genetic epidemiology of cardiovascular disease, utilising data for the cholesteryl ester transfer protein gene (CETP), the hepatic lipase (LIPC) gene and the 15- lipoxygenase (ALOX15) gene on a total of 6,487 individuals from three Western Australian studies. Results of these analyses suggested single nucleotide polymorphisms (SNPs) and haplotypes in the CETP gene were associated with increased plasma high-density lipoprotein cholesterol (HDL-C). SNPs in the LIPC gene were also associated with increased HDL-C and haplotypes in the ALOX15 gene were associated with risk of carotid plaque among individuals with premature CHD. The research presented in this thesis is both novel and important as it provides methods for the analysis of haplotypic associations with a range of response types, while incorporating information about haplotype uncertainty inherent in populationbased studies. These methods are shown to perform well for a range of simulated and real data situations, and have been written into a statistical analysis package that has been freely released to the research community.

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Makubalo, Zola. "Mutation screening of candidate genes and the development of polymorphic markers residing on chromosome 19q13.3, the progressive familial heart block I gene search area". Thesis, Stellenbosch : Stellenbosch University, 2000. http://hdl.handle.net/10019.1/51838.

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Thesis (MSc)--Stellenbosch University, 2000.
ENGLISH ABSTRACT: Progressive familial heart block type I (PFHBI) is a cardiac ventricular conduction disorder of unknown cause associated with risk of sudden death, which has been described in several South African families. Clinically, PFHBI is characterised by right bundle branch block on ECG, which may progress to complete heart block, necessitating pacemaker implantation. The disease shows an autosomal dominant pattern of inheritance with evidence of genetic anticipation. Using genetic linkage analysis, the PFHBI-causative gene was mapped to a 10 eentimorgan (cM) gene-rich area of chromosome (C) 19q13.3, which has, subsequently, been reduced to 7cM by fine mapping with polymorphic dinucleotide (CA)n short tandem repeat (STR) markers. Several attractive candidate genes, including muscle glycogen synthase (GSY 1) and histidine-rich calcium binding protein (HRC), lie within this region. The aim of the present study was two-fold: 1) to identify and characterise tetranucleotide (AAAT)n STRs within the PFHBI critical region that could be developed as polymorphic markers for use in genetic fine mapping and 2) to screen selected regions of GSY 1and HRC, positional candidate genes, for the presence ofPFHBI-causing mutation(s). Cosmids harbouring CI9q13.3 insert DNA were screened for the presence of (AAAT)n STRs by dot blot and Southern blot hybridisation using a radiolabelled (AAAT)lO oligonucleotide probe. To characterise the harboured (AAAT)n STRs, the positively hybridising fragments identified by Southern blot were sub-cloned, sequenced and primers designed from the unique repeat-flanking sequences. These primers were used to genotype the (AAAT)n repeat locus to assess its polymorphic nature in a panel of unrelated individuals. Alternatively, vectorette PCR, a rapid method of identifying repeat sequences and obtaining the flanking sequences in large inserts, was employed to develop polymorphic markers from the positively hybridising clones. Selected exons of GSY1 and HRC were screened for the presence of potentially disease-causing mutations by PCR-SSCP analysis and direct sequencing, respectively, in PFHBI-affected and unaffected family members. Of the available cosmid clones that gave strong signals on dot blot and Southern blot hybridisation, three, 29395, 24493 and 20381, were located within the critical PFHBI area and were used for marker development. An interrupted (AAAT)n repeat motif (n less than 5) was identified in cosmid 29395, however, the repeat locus was not polymorphic in the tested population. No (AAAT)n motif, single or repeated was observed in the partial sequence of the sub-cloned fragment of cosmid 24493. Using vectorette peR, no repeated (AAAT)n motif was identified on sequencing the generated products in either cosmid 24493 or 2038l. However, diffuse single AAAT motifs were detected in both cosmids. Exons 4, 5, 11, 12 and 16 of GSY 1, containing domains that are conserved across species, and the conserved eterminus- encoding exons 2-6 of HRC were selected for screening for potential PFHBI-causing mutation(s). However, no sequence variations were detected. The interrupted (AAAT)n repeat identified in cosmid 29395 was not polymorphic, which confirmed reports that complex repeats, especially those containing AAAT motifs of less than 6 repeats, are not polymorphic. One possible explanation for the absence of a repeated AAAT motif in cosmids 24493 and 20381, which both gave positive hybridisation signals, is that the low annealing temperature of the AfT -rich repeat-anchored primers used in vectorette peR may have resulted in transient annealing to the diffuse single AAAT motifs detected on sequencing. The screened regions of candidate genes GSYI and HRC were excluded from carrying the disease-causing mutation(s). The availability of new sequence data generated by the Human Genome Project will influence future strategies to identify the PFHBI gene. Electronic searches will allow identification of STR sequences for development of polymorphic markers and gene annotation will allow selection of new candidate genes for mutation screening.
AFRIKAANSE OPSOMMING: Sien volteks vir opsomming

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Fournier, Caroline. "Genetic investigation of vascular diseases in the French-Canadian population". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0030/MQ64355.pdf.

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Zhian, Samaneh. "Molecular Genetic Analysis of CRELD1 in Patients with Heterotaxy Disorder". PDXScholar, 2011. https://pdxscholar.library.pdx.edu/open_access_etds/410.

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Heterotaxy refers to the abnormal arrangement of internal organs in relation to each other. Model organism studies have shown that functions of more than eighty genes are required for normal asymmetric left-right organ development. CRELD1 has been shown to be necessary for proper heart development and mutations in CRELD1 are known to increase risk of cardiac atrioventricular septal defects (AVSD). AVSD is the most common form of heart defect associated with heterotaxy, and we have previously shown that some individuals with heterotaxy-related AVSD have mutations in CRELD1. Therefore, we propose to examine the CRELD1 gene in a large sample of patients with heterotaxy syndrome. Our goal was to determine if mutations in CRELD1 are associated with other manifestations of heterotaxy or if they only coincide with AVSD. To achieve this aim, a sample size of 126 patients with heterotaxy collected by Dr. Belmont, Baylor college of Medicine, Texas, with approximately 66% of the heterotaxy population with different types of heart defects, were used for this study. Ten exons, promoter regions, and regulatory elements in the introns of CRELD1 gene were sequenced and analyzed. In this study three different heterozygous missense mutations in CRELD1 were identified in three unrelated individuals. These three individuals were diagnosed with different forms of heart defects in addition to AVSD. All three mutations were identified in highly conserved regions of CRELD1 possibly altering the CRELD1 properties. This demonstrates that mutations in CRELD1 may increase the susceptibility of AVSD in heterotaxy population. This information can help us to find factors effecting disease susceptibility in heterotaxy patients since the heart defects are a complex trait with incomplete penetrance.

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Yako, Yandiswa. "Bioinformatics-based strategies to identify PFHBII-causing and HCM main locus and/or HCM modifying mutations". Thesis, Stellenbosch : University of Stellenbosch, 2004. http://hdl.handle.net/10019.1/16473.

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Thesis (MSc)--University of Stellenbosch, 2004.
ENGLISH ABSTRACT: Progressive familial heart block type II (PFHBII) is an inherited cardiac conduction disorder of unknown aetiology, which has been described in a South African family. The disorder was mapped to a 2.9 centimorgan (cM) locus on chromosome 1q32.2-32.3. Clinically, PFHBII manifests cardiac conduction aberrations, that progress to a disease of the heart muscle, dilated cardiomyopathy (DCM). DCM is also reported as an end phase in hypertrophic cardiomyopathy (HCM), another heart muscle disorder. These cardiomyopathies are genetically heterogeneous with some of the genes reported as causes of both disorders. Therefore, genes identified as causes of HCM and DCM were considered plausible candidates for PFHBII mutation analysis. Additionally, this study provided an opportunity to assess potential modifiers of HCM. HCM exhibits marked phenotypic variability, observed within and between families harbouring the same causative mutation. Genes within the PFHBII locus were selected for PCR-SSCP analysis based on homology to genes previously reported as causing conduction system disorders associated with arrhythmias, DCM and/or HCM. Results were confirmed by direct sequencing and association between the detected variants and HCM parameters was assessed using a quantitative transmission disequilibrium test (QTDT). Eleven plausible candidate genes were selected within the PFHBII locus and two of the genes, PFKFB2 and ATF3, that encode for 6-phosphofructo-2,6-bisphosphatase (PFK-2/FBPase-2) and activating transcription factor 3 (ATF3), respectively, were analysed for PFHBII-causing and HCM main locus and/or HCM modifying mutations. Mutation analysis of PFKFB2 and ATF3 in the PFHBII family revealed no PFHBII causal mutation. PFKFB2 and ATF3 were later localised outside the PFHBII locus, and, therefore, were excluded as PFHBII plausible candidates. Further analysis of the two genes for HCM main locus and/or HCM modifying mutations in the HCM panel identified several sequence variants. QTDT analysis of these variants showed no significant association. Completion of the Human Genome Project (HGP) and annotation of new genes within the PFHBII locus allowed the identification of more PFHBII plausible candidate genes. Identification of causal mutations in plausible PFHBII candidate genes will allow molecular diagnosis of PFHBII pathophysiology. Furthermore, identification of both HCM-modifying and HCM-causing genes will give insight into the phenotypic variability noted among South African HCM-affected individuals and into the molecular cause of the disease among individuals with HCM-like clinical features.
AFRIKAANSE OPSOMMING: Progressiewe familiële hartblok tipe II (PFHBII) is ŉ oorgeërfde hart geleidingsiekte van onbekende etiologie wat in ŉ Suid-Afrikaanse familie beskryf is. Die siekte is ŉ 2.9 sentimorgan (cM) lokus op chromosoom 1q32.2-32.3 gekarteer. Klinies presenteer PFHBII met geleidingsfwykings wat uitloop op gedilateerde kardiomiopatie (DCM). DCM word ook gerapporteer as ŉ endfase in hipertrofiese kardiomiopatie (HCM), ŉ ander hartspiersiekte. Die kardiomiopatieë is geneties heterogeen, met ŉ aantal gene wat as oorsaak van altwee siektetoestande gerapporteer word. Daarom is alle gene wat geïdentifiseer is as oorsake van DCM en HCM, as moontlike kandidaatgene vir PFHBII mutasieanaliese beskou. Bykomend het hierdie studie die geleentheid gebied om potensiële modifiseerders van HCM te assesseer. HCM toon beduidende fenotipiese variasie binne en tussen families wat dieselfde siekteveroorsakende mutasie het. Gene binne die PFHBII-lokus is geselekteer vir PCR-SSCP-analiese gebaseer op homologie met gene wat voorheen gerapporteer is om betrokke te wees by geleidingsiesisteemsiektes, geassosieerde arritmieë, DCM en/of HCM. Resultate is bevestig deur volgordebepaling. Assosiasie tusssen ontdekte variante en die siekteparameter is bepaal met ŉ kwantitatiewe transmissie disekwilibrium toets (QTDT). Elf moontlike kandidaatgene in die PFHBII-lokus is geselekteer en twee van die gene, PFKFB2 en ATF3, wat kodeer vir 6-fosfofrukto-2,6-bifosfatase (PFK-2/FBPase-2) en aktiveringstranskripsiefaktor 3 (ATF3) respektiewelik, is vir PFHBII-oorsakende en HCMhooflokus en/of HCM-modifiseerende mutasies ondersoek. Mutasie-analiese van PFKFB2 en ATF3 in die PFHBII-familie het nie ŉ siekteveroorsakende mutasie onthul/uitgelig nie. PFKFB2 en ATF3 is later buite die PFHBII-lokus geplaas en dus ook as moontlike PFHBII-kandidate uitgesluit. Verdere ondersoek van díe twee gene vir HCM-hooflokus en/of HCM-modifiserende mutasies in die HCM-paneel het ŉ aantal volgorde variante geïdentifiseer. QTDT-analiese van die variante het geen beduidende assosiasies aangetoon nie. Voltooiing van die Menslike Genoom Projek (HGP) en annotasie van nuwe gene in die PFHBIIlokus het tot die identifikasie van verdere moontlike PFHBII-kandidaatgene gelei. Identifikase van siekte-veroorsaakende mutasies in die moontlike PFHBII-kandidaatgene sal die molekulêre diagnose van PFHBII toelaat en insig in die patofisiologie van die siekte gee. Verder, identifikasie van beide HCM-veroorsakende of HCM-modifiserende gene kan insig gee in die fenotipiese varieerbaarheid wat onder Suid-Afrikaanse HCM-geaffekteerde individue waargeneem word en ook in die molekulêre oorsake van die siekte in individue met HCMsoortige kliniese kenmerke.

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Chan, Kin-wang, i 陳健宏. "Study of the in vivo role of TSPYL2 in transgenic mice". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38225049.

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Pocathikorn, Anothai. "Low density lipoprotein receptor-related protein (LRP) and its mRNA : influence of genetic polymorphisms, a fat load and statin therapy". University of Western Australia. School of Surgery and Pathology, 2006. http://theses.library.uwa.edu.au/adt-WU2006.0117.

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[Truncated abstract] The low density lipoprotein receptor-related protein (LRP), a member of the low-density lipoprotein (LDL) receptor gene family is involved in numerous biological processes including lipoprotein metabolism. This thesis concerns investigations into some aspects of LRP metabolism/regulation and possible roles in coronary artery disease (CAD). Specific aims were: to investigate the association between polymorphisms in the LRP gene and in its associated protein, the lipoprotein receptor-associated protein (RAP), with the risk of CAD; to extensively examine the influence of the LRP exon 22 C200T polymorphism on lipid metabolism; to develop and characterise assays for the mRNA expression of LRP and 2 other genes relevant to lipid metabolism, the LDL receptor (LDLR), and HMG CoA reductase (HMGCR); and finally, to apply the latter techniques to studies on the influence of genetic variation in LRP, and dietary and drug interventions, on LRP, LDLR and HMGCR mRNA expression in nucleated blood cells from healthy human subjects. Six hundred CAD subjects and 700 similarly aged controls were genotyped for 8 LRP gene polymorphisms as well as for the RAP V311M polymorphism. ... In the final phase of my studies, I examined the influence of 4 weeks therapy with a cholesterol lowering drug, an HMGCR inhibitor, atorvastatin (20mg daily), on the mRNA expression of LDLR, LRP and HMGCR in human nucleated blood cells. Twelve normal Caucasian male subjects aged 49 ? 5 (SD) years were studied. Plasma total cholesterol and LDL-C decreased by averages of 29 % and 41 % after the 4 week period. This was accompanied by an elevation in LDLR mRNA expression by approximately 30 35 %. In contrast, there was no significant effect on LRP and HMGCR mRNA expression. In conclusion, the original findings in this thesis included: demonstration of a strong influence of the LRP exon 22 C200T polymorphism on coronary artery disease and LDLR expression, but without a clear effect on fasting or postprandial lipid levels; data on the biological variation in LDLR and LRP gene expression in nucleated blood cells from normal subjects; the influence of an oral fat load on the expression viii of these genes, finding that LDLR was significantly depressed; and finally, the observation that statin therapy upregulated LDLR in nucleated blood cells.

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Kuek, Conchita Maria. "Hereditary haemochromatosis and the C282Y genotype : implications in diagnosis and disease". University of Western Australia. School of Surgery and Pathology, 2003. http://theses.library.uwa.edu.au/adt-WU2004.0024.

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[Truncated abstract. Please see the pdf format for the complete text.] The discovery of the C282Y mutation and its role in the development of hereditary haemochromatosis has allowed a greater understanding into the effects of iron overload and its involvement in other conditions such as diabetes and heart disease. It has also allowed the better classification of heterozygotes, who were previously only diagnosed through the use of family studies. There are however, areas of conflict between phenotyping and genotyping methods. My research involved examining the relationship between Haemochromatosis and certain diseases such as diabetes and heart disease; genotyping versus phenotyping discrepancies and the possible interaction of secondary mutations. In Chapter 3 a population study was undertaken with the aim of comparing genotyping versus phenotyping methods as well as increasing general practitioner awareness regarding hereditary haemochromatosis and its diagnosis. It was determined that a minimum of 5000 subjects would be required to give the study sufficient power. Individuals were to be between the ages of 20—40 years, and thus presumably presymptomatic. Participation was entirely voluntary and a consent form was to be signed. Recruitment of subjects proved to be difficult and there was a selective bias towards individuals already displaying symptoms of haemochromatosis. In total less than a 100 subjects were recruited for the study. There were several issues encountered in the implementation of this study. Firstly the number of GPs participating was probably insufficient to recruit the subjects required. A more extensive campaign was probably required to enroll more GPs. Secondly it is very difficult for a busy GP to find the time necessary to explain the study to each of his patients and to get them to sign the consent form. Finally a bias developed in some of the requests. The subjects participating in this study were supposed to be random but in many cases the GPs had enrolled them in the study because they had symptoms of iron overload. In effect the biggest obstacle this study faced was the recruitment of subjects. Due to the small number of subjects little statistical data could be obtained from this study. It was noted, however, that genotyping methods detected two individuals who were homozygous for the C282Y mutation. Both also had increased transferrin saturation levels. Phenotyping detected 5 individuals with increased transferrin saturation. The three others detected via phenotyping were C282Y heterozygotes. Haemochromatosis has long been though to be related to the development of diabetes due to the effect of iron overload on the pancreas. If this is so it would be logical to assume that the prevalence of haemochromatosis would be higher in a diabetic population. Chapter 4 examined the possibility that diabetics have a higher frequency of the C282Y mutation. A population group consisting of 1355 diabetics was genotyped for the C282Y mutation and iron studies were performed on all heterozygotes and C282Y homozygotes. Initial findings indicated that there was a significant difference between the diabetic and control population. However, this finding was the opposite of what was expected, there seemed to be a decreased frequency of the Y allele in the diabetic population rather than an increased one. The control and diabetic populations were not matched in terms of ethnicity. The removal of the ethnic bias in the diabetic population altered the statistics so there was no longer a significant difference between the two groups. This study highlighted the importance of using appropriate control populations as comparison groups. The final results of the study indicated that there was no significant difference between the diabetic population and the control population. This would seem to indicate that there is not an increased occurrence of the C282Y mutation in the diabetic population when compared to the control group. Chapter 5 considered the possible association between C282Y heterozygosity and cardiovascular disease as well as the potential for early mortality. Several recent studies have indicated that C282Y heterozygosity may be a risk factor for the development of atherosclerosis, possibly on the basis of increased iron loading. Using a control population and a population of individuals with known coronary events the incidence of the C282Y mutation was compared against other risk factors. C282Y heterozygosity did not appear to be a risk factor for atherosclerosis. There was however, a statistically significant link between increased ferritin in women and carotid plaques. A population of elderly women was genotyped in order to examine the effects of C282Y heterozygosity on longevity. The first hypothesis addressed in chapter 5 was that C282Y heterozygosity was a risk factor for the development of coronary heart disease.

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Sznajer, Yves. "Etude des manifestations cardiovasculaires chez les patients présentant un syndrome de Noonan porteurs de mutation au sein du gène PTPN11: rôles des gènes de la voie de signalisation des MAP kinases pour les syndromes apparentés". Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210210.

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Les patients décrits initialement par J. Noonan se ressemblent et ont une cardiopathie congénitale :soit une sténose valvulaire pulmonaire (SVP), soit une persistance du canal artériel. Avant la découverte du premier gène responsable de ce qui est devenu le syndrome de Noonan, cinq études de cohortes décrivant ces patients ont répertorié la prévalence de SVP mais le spectre des cardiopathies semble large, n’a pas été décrit de manière exhautive et aucune hypothèse n’est émise ou ne fait de lien entre ces différentes manifestations cardiaques et une compréhension intégrée du développement embryonnaire. Le gène PTPN11 est le premier gène identifié chez 40% de ces patients. Une corrélation existe entre la présence d’une mutation et la survenue de SVP de même qu’entre l’absence de mutation et la présence d’une cardiomyopathie hypertrophique. Six études de cohortes ont repris la description des mutations identifiées au sein du gène PTPN11 et les phénotypes associés, mais les cardiopathies n’ont pas été systématiquement ou spécifiquement analysées (tant au sein des groupes de patients porteurs de mutation que de ceux sans mutation). Le syndrome LEOPARD est allélique du syndrome de Noonan depuis que des mutations spécifiques au sein des exons 7,12 et 13 du gène PTPN11 ont été identifiées chez 95% des patients.

Afin d’appréhender les implications possibles du gène PTPN11 dans la survenue des cardiopathies chez les patients porteurs de ces deux syndromes, nous avons conduit une étude chez 272 patients au syndrome de Noonan et une étude chez 19 patients porteurs du syndrome LEOPARD. Parmi la cohorte de patients atteints du syndrome de Noonan, 104 ont été diagnostiqués porteurs d’une mutation du gène (38%). Une prévalence de survenue de cardiopathies affectant les structures droites du cœur se dégage chez les patients identifiés porteurs d’une mutation avec une différence significative pour la SVP, une tendance est relevée pour le canal atrio-ventriculaire et la communication inter-auriculaire de type Ostium Secundum. L’absence de mutation est corrélée avec la survenue de cardiomyopathie hypertrophique et de cardiopathies du cœur gauche. Parmi les patients atteints du syndrome LEOPARD, il n’existe pas de différence statistiquement significative pour les patients porteurs d’une mutation ou non et/ou pour une cardiopathie particulière.

Toutes les mutations identifiées du gène PTPN11 sont des mutations ‘faux-sens’. Ce gène appartient à la famille des gènes codant pour une protéine tyrosyl phosphatase, SHP-2, ne possédant pas de récepteur trans-membranaire. Cette phosphatase est impliquée dans la voie de signalisation cellulaire des MAP (‘Mitogen-activated protein’) kinases dont l’expression est ubiquitaire et inclut le coeur. Depuis nos travaux, le concept de syndrome « neuro-cardio-facio-cutané » est établi puisque, à ce jour, 9 gènes (SOS1, RAF1, BRAF, KRAS, NRAS, HRAS, NF1, SPRED1 et SHOC2), tous impliqués dans la voie de signalisation RAS (voie des MAP kinases) sont identifiés. Un spectre phénotypique existe avec des signes communs mais aussi distinctifs chez les patients présentant le syndrome de Noonan, le syndrome LEOPARD, le syndrome de Costello, le syndrome Cardio-Facio-Cutané (CFC), le syndrome « Noonan-NF1 », le syndrome de Legius et le syndrome « Noonan/Multiple Giant Cell Lesion ». Nous rapportons enfin l’observation d’une patiente atteinte du syndrome CFC et porteuse d’une mutation (p.R257Q) au sein du gène BRAF ayant développé une cardiomyopathie hypertrophique.

Ces travaux de cohortes de patients au phénotype du syndrome de Noonan, du syndrome LEOPARD et cette dernière description d’une patiente au syndrome CFC ont permis de participer à la découverte de l’implication d’une voie de signalisation cellulaire dont l’origine génétique est maintenant démontrée. Les résultats de nos travaux réalisés depuis 2002 auront permis, avec les équipes travaillant sur le même sujet, d’orienter les investigations et les nouveaux projets de recherche qui étudient spécifiquement le rôle du gène PTPN11 dans l’embryologie du cœur. Les études des orthologues (zebrafish, murin et Drosophila) porteurs à l’état hétérozygote d’une mutation du gène PTPN11 permettent d’intégrer les anomalies phénotypiques et cardiaques observées. Ces études permettent de postuler les effets cellulaires produits par les mutations chez les patients atteints du syndrome de Noonan et chez les patients atteints du syndrome LEOPARD engendrant in vitro une activation de la phosphatase (effet « gain de fonction ») pour les premiers ou une réduction de l’activité phosphatase (« dominant négatif ») mais engendrant un effet gain de fonction in vivo. Nous discutons les connaissances acquises, les compréhensions obtenues et intégrées et traçons enfin les perspectives offertes par ces travaux.

Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished

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Rondelet, Benoît. "Médiation humorale de l'hypertension artérielle pulmonaire dans un modèle de cardiopathie congénitale à shunt systémo-pulmonaire chez le porcelet en croissance". Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210373.

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Pennington, Catherine Margaret. "Genetic aspects of human prion diseases". Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/24216.

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Introduction: Human prion diseases are progressive, fatal neurological conditions linked to conformational changes in the structure of the prion protein. Prion diseases may be sporadic (sporadic Creutzfeldt-Jakob disease or sCJD, Sporadic Fatal Insomnia), acquired (variant CJD, iatrogenic CJD, kuru) or genetic (genetic prion disease, gPD). gPD is due to a disease-specific point or octapeptide repeat insertion (OPRI) mutation in the prion protein gene (PRNP). Numerous different PRNP mutations have been described. In some cases of gPD the phenotype may closely resemble that of sCJD, and it can be impossible to distinguish sporadic from genetic cases without genetic screening. The clinico-pathological phenotype of gPD is highly variable, both between different mutations and even within families carrying the same mutation. This variability can be partly explained by a polymorphism at codon 129 of PRNP. Codon 129 encodes either methionine or valine, and the status of both the mutated and wild-type alleles may influence disease susceptibility and phenotype. Codon 129 may also affect the manifestations of sporadic and acquired prion disease. Homozygosity for methionine at codon 129 is over-represented in both sporadic CJD (sCJD) and variant CJD (vCJD); indeed all definite or probable clinical cases of vCJD seen to date have been homozygous for methionine. Other polymorphisms of PRNP have been found in a small number of patients with sporadic and variant CJD. The significance of these polymorphisms has not been fully investigated. It is likely that other, as yet unidentified, genetic factors also play a role in influencing susceptibility to prion diseases and the clinico-pathological phenotype. A recent genome wide association study of vCJD patients found codon 129 to be the main genetic risk factor for vCJD, but did identify other candidate loci that may contribute to disease susceptibility. Work is in progress to carry out genomic screens for other, novel polymorphisms in 309 patients with sCJD and 118 patients with vCJD. Aims: The aims of the work described in this MD thesis are: 1) To review all cases of gPD on the database of the National Creutzfeldt-Jakob Disease Research and Surveillance Unit. The clinico-pathological phenotype, investigative findings and family history will be reviewed in detail. The findings will be compared with those cases of gPD previously described, in particular with cases seen in other European countries. The incidence and prevalence of these diseases in the UK will also be assessed. 2) To review cases of sCJD and vCJD with novel PRNP polymorphisms of uncertain significance. The clinico-pathological phenotype will be reviewed in detail to attempt to establish if these novel polymorphisms exert any influence over disease susceptibility or phenotype. Results: 159 cases of gPD were identified between 1970 and 2009, representing 7.8% of the prion disease (of any type) cases referred to the NCJDRSU over this time period. 17 different PRNP haplotypes were identified: P102L-129M, P105L-129V, A117V-129V, S132I-129M, Y163X, D167G-129M, D178N-129M, D178N-129V, E200K-129M, D202N-129V, V210I-129M, Q212P-129M, 2-OPRI, 4-OPRI, 5- OPRI, 6-OPRI, 7-OPRI. The clinicopathological phenotypes were highly variable and often difficult to distinguish from sCJD. The highest number of cases was caused by the 6-OPRI, most of which belonged to a single kindred. Several cases in the 4-OPRI group were found to share an additional risk allele, rsl029273C. In may be that this mutation is not pathogenic unless this risk allele is also present. This raises the possibility that other as yet unidentified genetic risk factors exist which influence gPD susceptibility and clinicopathological phenotype. Overall 61.4% of cases tested had a positive cerebrospinal fluid (CSF) 14-3-3, 90.0% an elevated SI00b, 23.1% had Magnetic Resonance Imaging (MRI) of the brain showing basal ganglia or cortical high signal, and 18.1% had an electroencephalogram (EEG) showing triphasic periodic complexes. A positive family history of prion disease was present in 57.9% of cases. Discussion: The range of point mutations and OPRI seen in the UK is considerable, but the majority of cases were due to 6-OPRI, E200K, or PI 02L. The UK differs from the rest of the world in that E200K is not the commonest mutation, due to the presence of a large British kindred with the 6-OPRI. Even within the larger kindreds, the clinicopathological phenotype remained very variable. Some distinctive features which may act as pointers towards gPD were found, such as a linear pattern of PrPSc deposition in the cerebellum seen in E200K-129M cases. Analysing the data in the smaller groups should be done with caution, and further large international studies are needed in order to truly determine the influence of factors such as codon 129 status. As with other forms of prion disease, there is an excess of individuals with methionine homozygosity at codon 129. It is unclear whether or not PRNP mutations in cis with valine at codon 129 will result in prion disease at an older age or with a different phenotype, or if these are not actually pathogenic in this genetic context. In the case of 4-OPRI, it appears that an additional risk allele is required for the development of disease, and it remains to be seen if other additional genetic factors will be found to influence disease susceptibility and phenotype. A relatively small percentage of cases had EEGs showing periodic triphasic waves, or basal ganglia or cortical high signal on MRI. CSF SI00b was more sensitive than 14-3-3, the reverse of the pattern seen in sCJD. A pattern of a negative 14-3-3 and a very high SI00b should lead to suspicions of gPD. The current diagnostic criteria for gPD are relatively strict, and may exclude some individuals who have neuropathologically confirmed prion disease (without PRNP genotyping) and several second degree relatives with gPD. This is a potential problem, especially as the neuropathological appearances cannot be relied upon to distinguish sporadic from genetic disease. Particular attention should be paid to the family history and any subtle unusual neuropathological appearances to try and reduce the risk of gPD cases being missed. In conclusion, gPD remains a difficult condition to diagnose and study. Large systematic collaborative studies are essential to increase our understanding of these rare conditions.

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12

Guo, Youling, i 郭友玲. "Genetic and genomic mapping of common diseases". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B50533861.

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Genome-wide mapping of susceptibility genes was conducted in two complex disorders of hypertension and epilepsy, allowing the dissection of the genetic architecture of these common diseases and related quantitative traits. The study performed comprehensive genetic analyses in a genome-wide scale, using different structure of data – sib-pairs and case-control samples. To identify genes influencing hypertension and blood pressure, a combined linkage and association study was conducted using over half a million SNPs genotyped in 328 siblings. Regions of significant linkage were identified for blood pressure traits on chromosomes 2q22.3 and 5p13.2, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P < 7  10-5) for hypertension. One candidate gene, PDC, was replicated in the family-based association tests. A two-stage genome-wide association study (GWAS) was performed in a total of 1,087 cases and 3,444 controls, to identify common susceptibility variants of epilepsy in Chinese. The combined analysis identified two association signals in CAMSAP1L1, rs2292096 [G] (P=1.0×10-8, OR =0.63) and rs6660197 [T] (P=9.9×10-7, OR=0.69), which are highly correlated, achieving genome-wide significance. One SNP (rs9390754, P = 1.7 × 10-5) in GRIK2 was refined as a previously-implicated association. In addition to SNPs, the assessment of CNVs in GWAS was performed, which could provide valuable clues to discover genes contributing to the heritability of epilepsy. A genome-wide scan for epilepsy through the use of DNA pooling also provides an alternative approach to reducing the substantial cost and thus increase efficiency in large-scale genetic association studies. The genome-wide mapping studies in families and unrelated individuals are complementary and together offer a comprehensive catalog of common variations and structural variants implicated for both quantitative and qualitative traits.
published_or_final_version
Psychiatry
Doctoral
Doctor of Philosophy

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13

Lau, Kin-chong, i 劉健莊. "Microarray-based investigations of genetic diseases". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B45894760.

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14

Roscioli, Tony Clinical School Prince of Wales Hospital Faculty of Medicine UNSW. "The genetic basis of veno-occlusive disease with immunodeficiency syndrome". Awarded by:University of New South Wales. Clinical School - Prince of Wales Hospital, 2007. http://handle.unsw.edu.au/1959.4/40599.

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This thesis addresses the genetic basis of a rare autosomal recessive primary immunodeficiency disorder with the characteristic additional feature of venoocclusive disease of the liver (VODI). The interest in this condition was stimulated both by the potential to identify the genetic basis of a rare immunodeficiency and the opportunity to gain an insight into the biological basis of hepatic veno-occlusive disease, a poorly understood condition that is encountered most frequently in Australia as a consequence of bone marrow transplantation. The gene responsible for VODI was identified by homozygosity mapping and DNA sequence analysis of positional candidates and was shown to be the PML Nuclear Body expressed protein Sp110. This is the first time a PML Nuclear Body protein has been shown to be involved in immunodeficiency disorder. Subsequent immunofluorescence studies of affected patient cell lines showed absence of Sp110 in patient B cells. The role of SP110 alleles in the susceptibility of bone marrow transplant patients to hepatic veno-occlusive disease was investigated using a cohort of patients from the Fred Hutchinson Cancer Center, Seattle. A SNP association study identified initial evidence for an association, but the study lacked sufficient power after correction for multiple testing. Contemporaneously, Dr Igor Kramnik published a report that the murine homologue of Sp110, Ifi75 (also termed Ipr1) was deleted in mice that were supersusceptible to infection with Mycobacterium tuberculosis. A further SNP association study was therefore performed utilising a NSW cohort of Mantouxpositive South East Asian migrants, which detected evidence that alleles of SP110 may be associated with progression of M. tuberculosis infection. Again, the limited size of this cohort precluded definitive findings.

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15

Wong, Hoi-man Emily, i 黃凱敏. "Genome-wide association analyses on complex diseases: from single-nucleotide polymorphism to copy numbervariation". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50534099.

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Complex diseases, unlike Mendialian diseases, are often characterized by genetic heterogeneity and multifactorial inheritance, involving defects in genes from the same or multiple alternative pathways. Many congenital diseases and psychiatric disorders are complex diseases, and incur heavy health care burden on the society. With the advancement in high-throughput genotyping technologies and the availability of the human single nucleotide polymorphism (SNP) catalogue, genome-wide association study (GWAS) has been widely used to investigate the genetic component of complex diseases. Copy number variations (CNV) can also be identified using the data from the same SNP array. Aiming to identify more disease susceptibility loci for complex diseases, separate GWAS using a case-control design were conducted on anorectal malformations (ARMs) and schizophrenia. ARMs are rare congenital diseases with heterogeneous phenotypes which could probably be explained by the genetic heterogeneity among patients, while schizophrenia is a common psychiatric disorder that is well known for its multigenic inheritance. The GWAS studies on ARM and schizophrenia included 4,369 (patients: N=363; controls: N=4,006) and 1,231 Han Chinese (patients: N=381; controls: N=850) respectively. The two studies were mainly focused on investigating the contribution of rare CNVs to the diseases, involving analyses on global CNV burden, rare CNV association, protein-protein interaction (PPI) network, pathway and chromosomal aberrations. The associations of SNPs with ARMs were also examined. Apart from elucidating the genetic components in these two diseases, a systematic analysis on four CNV detection programs (CNV partition, PennCNV, QuantiSNP and iPattern) was also undertaken. In the study of schizophrenia, a new approach in CNV filtering which was based on latent class analysis was adopted to gather information from multiple CNV prediction programs. The study of ARMs revealed 79 genes which were disrupted by CNVs in patients only. In particular, a de novo duplication of DKK4 (an antagonist of WNT signaling) was identified, and addition of Dkk4 protein was demonstrated to cause ARMs in mice. Another 10 genes uniquely disrupted in ARMs patients are also related to WNT signaling. Interestingly, this pathway was also significantly inferred by CNV in patients with schizophrenia. A different set of genes related to WNT signaling was disrupted in ARMs patients and patients with schizophrenia. WNT signaling is crucial for the development of multiple parts in the embryo. The contribution of different WNT signaling pathways at different development stages may vary. Apart from the WNT signaling pathway, other genes with biological relevance were also implicated in the two studies through gene-network and pathway analyses. The results from these two GWAS studies support our existing understanding of complex diseases that defects in various interacting genes could contribute to the same disease. In summary, the CNV results from the two studies have demonstrated the genetic heterogeneity nature of these two complex diseases. The findings also uncovered a set of putative disease candidate genes, which can be used as reference materials for future genetic research for ARMs and schizophrenia.
published_or_final_version
Psychiatry
Doctoral
Doctor of Philosophy

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16

Nitoiu, Daniela. "Insights into molecular and functional mechanisms behind inherited heart and skin disorders". Thesis, Queen Mary, University of London, 2015. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8911.

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Desmosomes are macromolecular, dynamic and adaptable complexes that connect intermediate filaments of neighboring cells in a variety of tissues, generating a large mechanically resilient structure. The importance of maintaining desmosome homeostasis for tissue integrity and optimal organ function has been revealed through the identification of desmosome-associated disorders and mechanistic studies into desmosome regulation. This thesis focuses on inherited skin and heart conditions linked to mutations in desmosomal genes or in genes believed to be implicated in desmosome regulation. Part of this thesis is focused on the molecular analysis and identification of novel desmosomal mutations in patients clinically diagnosed with Arrhythmogenic Right Ventricular Cardiomyopathy, and the genetic diagnosis of patients with hypotrichosis, hypotrichosis and PPK or acral peeling skin syndrome. Patients were analysed using a number of different genetic techniques including custom capture array, HaloPlex targeted resequencing, exome capture and Sanger sequencing. Both novel and previously reported mutations were identified in DSP, DSC2, DSG2, PKP2, DSG4 or CSTA in patients diagnosed with these disorders. The molecular mechanisms behind mutations in the protease inhibitors cystatin A and calpastatin, leading to the skin disorders exfoliative ichthyosis and PLACK syndrome, were also investigated. In vitro analysis, using siRNA-mediated knockdown in the immortalised keratinocyte cell line HaCaT, demonstrated that these mutations, affecting the structure and function of the protease inhibitors, lead to deficient intercellular adhesion, possibly through the indirect regulation of desmosomal complexes through their target proteases.

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17

Zdravkovic, Slobodan. "Coronary heart disease in Swedish twins : quantitative genetic studies /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-771-5/.

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18

Ho, Wai-hung Daniel, i 何偉雄. "Genetic study of lumber disc degeneration". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42841215.

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19

Al-Abri, Mohammed Ali. "Genetic variability of health disorders in Ontario Holstein cows". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112310.

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Extensive emphasis on selection for milk yield with minimal attention to the animals' functional performance has increased the yield of North American dairy cattle. The high intensity of selection for production traits such as milk yield, protein yield and fat yield has also brought about a rapid increase in genetic relationships among animals. In dairy cattle, correlated response to selection for milk yield includes fertility and susceptibility to diseases. Although the high producing cows have greater net profit, they also have higher mammary and discarded milk costs associated with high production. Long-term genetic selection against clinically diagnosed diseases might be useful to diminish their incidence. The Scandinavian countries have incorporated the health traits into their selection indices. Canadian breeding programs realize the need to consider traits other than the yield in selection decisions. The objective of this study was to determine the genetic variability of various clinically diagnosed health traits. Data from 171 herds of the Ontario milk-recording program were used. These herds are collaborating with the University of Guelph (Dr. David Kelton) to record health traits. A major impediment to estimating heritabilities for the majority of the disorders was that the progeny group size per sire was not large enough to enable detecting a significant difference among sires. Hence, heritability estimates were not obtained for all the health disorders included in the study. The progeny group size per sire has to be increased such that there are at least 5 cases per progeny group to enable detecting a difference among sires. Heritability estimates for retained placenta and displaced abomasum in the first lactation were 0.067 and 0.212 respectively. The heritability estimate of cystic ovaries in the second lactation was 0.092. In the third lactation, the heritability estimate of mastitis was 0.10 whereas retained placenta had a heritability of 0.25.

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20

Kao, Yu-ping Patrick, i 高宇平. "Genetic association studies of lumbar disc degeneration (LDD)". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45154430.

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21

Lee, Kin-shing, i 李鍵成. "In vivo study of asporin function in cartilage tissues". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/207898.

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Asporin (ASPN) is a risk factor for osteoarthritis and intervertebral disc degeneration. Its expression increases with aging and degeneration. D14 (14 aspartate-repeat polymorphism) is the risk allele and D13 is the most common allele. In vitro studies suggest that Asporin functions as a negative regulator of Tgf-β signaling, an important stimulator of matrix formation in bone and cartilage. However, the in vivo role of Asporin in development or its involvement in the pathogenesis of degenerative cartilage diseases is unclear. Here, we use mouse as a model to study the impact of Asporin in the intervertebral discs of the spine. In wide type mice, we showed that Asporin is expressed and localized in the nucleus pulposus and annulus fibrosis of intervertebral discs, and the articular cartilage in knee joints. Furthermore, Asporin expressing cells in these tissues are active in Tgf-β signaling, suggesting a relationship between Asporin and Tgf-β signaling and a role in disc and articular joint maintenance. Using natural degeneration with aging, and models for induced degeneration in the mouse-tail discs, Asporin expression was shown to be up-regulated in nucleus pulposus and annulus fibrosis cells of degenerating intervertebral discs. These cells are also active in Tgf-β signaling supporting a potential relationship with the pathogenesis of disc degeneration. Transgenic mice overexpressing Asporin in cartilage tissues were generated to study this relationship and the impact on the differentiation and function of disc cells. Interestingly, overexpression of Asporin in the nucleus pulposus leads to enhanced production and deposition of extracellular matrix such as glycosaminoglycans, with concomitant changes in cell morphology, suggesting Asporin altered the extracellular matrix niche of resident nucleus pulposus cells. However, such changes are only observed in discs in the tail region but not in lumbar discs. We propose a relationship to mechanical loading as an environmental factor. Molecular analysis of transgene expressing cells showed Tgf-β signaling is active and its downstream target genes up-regulated. Furthermore, overexpression of Asporin enhances differentiation of notochordal-like cells (NCCs) in mouse nucleus pulposus toward the more mature nucleus pulposus cells (NPCs) and chondrocyte-like cells (CLCs) that are more abundant in the human nucleus pulposus and other larger animals that prompt to intervertebral disc degeneration. This study provided new insights into the function of Asporin in the pathogenesis of intervertebral disc degeneration. We proposed a model whereby Asporin, as a genetic risk factor, alters the extracellular environment of the nucleus pulposus, that in conjunction with environmental factors such as mechanical loading, enhances Tgf-β signaling, and consequentially, promotes the maturation of NCCs towards NPCs and CLCs, a hallmark of degenerative process proposed in human and other larger animal models. These transgenic mice provide the opportunity to better understand the relationship between genetic and environmental factors, and the molecular controls leading to the maturation process of NCCs in intervertebral disc degeneration.
published_or_final_version
Biochemistry
Doctoral
Doctor of Philosophy

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22

Tam, Chun-yee, i 譚雋怡. "Dissecting the physiological role of the novel lupus-associated C-type lectin-like protein CLEC16A". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206749.

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The CLEC16A locus has been identified as a susceptibility gene for multiple autoimmune diseases, including multiple sclerosis, type-I diabetes and systemic lupus erythematosus (SLE), in genome-wide association studies. CLEC16A encodes a novel C-type lectin-like protein, by virtue of a predicted C-type lectinlike domain (CTLD), with unclear function. Studies on the disease-associated SNPs have suggested that CLEC16A polymorphisms affect the expression of neighboring genes, while the effect on its own expression is unclear. Several functional studies have interrogated the physiological role(s) of CLEC16A in disparate directions. The Drosophila ortholog of CLEC16A, Ema, has been reported to regulate endosomal protein trafficking and the autophagic process, while CLEC16A has been found to participate in LPS-induced inflammatory cytokine response in rat astrocytes. Since there is not a consenting role ascribed to CLEC16A, this study was undertaken to investigate the functional involvement(s) of CLEC16A in mammalian cells and the expression of CLEC16A in lupus patients, with the attempt to comprehend the association between CLEC16A and SLE. By overexpressing in non-immune epithelial cells, CLEC16A was revealed to be an intracellular protein of ~130 kDa in size. CLEC16A displayed a punctated expression pattern, which did not co-localize with endosomes, lysosomes, autophagosomes or endoplasmic reticulum in steady state. When treated with rapamycin or serum-starved, CLEC16A-overexpressing cells exhibited a reduced autophagic response, suggesting that CLEC16A may have an inhibitory role in autophagy. Besides the predicted CTLD, motif prediction has also implicated an immunomodulatory role for CLEC16A. Due to the observed inhibition on autophagy, coupled with recent findings linking autophagy and inflammasome activation, the involvement of CLEC16A in NLRP3 inflammasome was investigated. By knocking down CLEC16A in the human macrophage-like THP-1 cells, CLEC16A was found to potentially regulate NLRP3 inflammasome activation via inhibiting the LPS-induced pro-IL-1aasynthesis. Finally, the expressions of the long and short isoforms, CLEC16A_V1 and CLEC16A_V2 of CLEC16A in PBMCs were compared between healthy controls and SLE patients. A higher CLEC16A_V1 expression was observed in SLE patients, whereas the reverse was found for CLEC16A_V2. The expressions of the isoforms, however, were not correlated with the disease severity and clinical manifestations. The finding that CLEC16A may inhibit autophagy is in contrast with the reported function of Ema in supporting autophagy, and such discrepancy could be because of the different cell systems used. The finding that CLEC16A may downregulate NLRP3 inflammasome activation has not been previously reported, and the mechanism(s) of such regulation warrant(s) future studies. The molecular basis of how CLEC16A regulates autophagy and inflammasome waits to be delineated. Such knowledge, together with information of where endogenous CLEC16A is expressed, shall incite better understanding of the contribution of CLEC16A to SLE development.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy

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23

Roy, Mélanie. "Identification and characterization of differentially expressed genes in response to Escherichia coli and Staphylococcus aureus in bovine mammary epithelial cells and mammary gland". Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98785.

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Bovine mammary glands respond to infection by foreign pathogens such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through changes in gene expression. Monitoring the gene expression profiles will contribute to better understanding of the pathology of mastitis, and provide important selective markers for future animal breeding programs. Using cultured bovine mammary duct epithelial cells and somatic cells from infected bovine mammary glands, this study first examined the existence of Toll Like Receptors in these two systems. In cultured duct epithelial cells stimulated with E. coli LPS, both TLR 4 and 2 mRNA up regulation was detected at 2h-72h and 12h-48h respectively. For S. aureus LTA TLR 2 mRNA was up regulated at 48 and 72h whereas for TLR 4 mRNA expression up regulation was detected at 24, 48, and 72h in comparison to the Oh (p<0.05). In the case of PGN, an abundant structural component of S. aureus, the expression of TLR 2 mRNA was significant (p<0.05) at 72h whereas TLR 4 mRNA expression increased at 24, 48, and 72h. The expression of these receptors was also monitored in milk cells from cows infected with either E. coli or S. aureus. However, results obtained from the milk cells were inconclusive due to the high individual variability. Afterwards, differential gene expression profiles were monitored by the Differential Display Polymerase Chain Reaction technique in the cultured duct epithelial cells in response to E. coli and S. aureus structural components. A total of 6 candidate fragments were identified for E. coli LPS induction, whereas only one fragment was identified for S. aureus LTA induction. After LTA induction, a specific band was found to be up regulated and confirmed to be GCP-2, a chemokine involved in neutrophil recruitment. In contrast, PGN induction resulted in no change in GCP-2 levels. In different preparations of cultured duct epithelial cells both GCP-2 and IL-8 were confirmed by real time PCR to be up regulated by LTA with a significance of (p<0.01) when compared to the control cells. In the case of the E. coli identified bands, a different approach is necessary to potentially confirm the origin of these fragments. Further large scale screening of the GCP-2 and IL-8 genes in dairy cattle is necessary to test for their potential use as targets to differentiate the mastitis resistant from the mastitis prone cows.

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24

Jenner, Kris Harlan. "The study of inherited diseases using recombinant DNA technology". Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670385.

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25

Broderick, Daniel J. "Mitral valve prolapse syndrome : a proposed treatment through respiratory rebalancing". Virtual Press, 1996. http://liblink.bsu.edu/uhtbin/catkey/1027110.

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Mitral Valve Prolapse Syndrome (MVPS) is a benign psychosomatic cardiac condition that can severely impair one's quality of life. Symptoms targeted in this study include, atypical chest pain, palpitations, anxiety, panic, and shortness of breath.This study was undertaken to examine the effects of a diaphragmatic breathing intervention on the symptoms and underlying mechanism of dysautonomia in a small group of symptomatic females with MVPS. The intervention was based on both yoga theory and cardiorespiratory empirical studies.Seven of eight participant's completed the nine week study using a single subject multiple baseline design across subjects. Participant's began a respiratory retraining intervention, in a weekly staggered pair start, after the first week of baseline measurement. Respiratory training consisted of a four week training in diaphragmatic breathing with home practice three times a day.Autonomic, behavioral, and cognitive systems were assessed. Dependent measures included State and Trait Anxiety, Anxiety Sensitivity, a Symptom Checklist, and Respiratory Sinus Arrhythmia (RSA). RSA is a current noninvasive measure of parasympathetic tone. Data on thoracic and abdominal respiratory predominance, respiration rate, diet, exercise, and adherence were also gathered.Data were analyzed via visual inspection of trends and phase average changes. Treatment effect sizes were calculated for standardized measures to indicate the meaningfulness of change.Two of the seven participants demonstrated a decrease in total symptom frequencies over the course of intervention. One participant demonstrated a weekly progression of lowered state anxiety scores from baseline through intervention. In terms of phase averages, three participants showed a lowering of state anxiety. All seven participants demonstrated lowered trait anxiety scores from pre to post intervention. Two of the seven participants demonstrated a meaningful pre to post intervention decrease in anxiety sensitivity. Respiratory training was effective in stabilizing abdominal respiration. Results regarding vagal tone could not be determined due to unreliable ECG data.In general, results were poor with several inconsistencies. Adherence rates were low and it did not appear that a therapeutic level of change in respiration rate was achieved. Controlling respiration rate may be a critical factor in the therapeutic effectiveness of respiratory retraining interventions.
Department of Counseling Psychology and Guidance Services

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26

Jagoda, Allison M. "Prevalence of abnormal heart rate acceleration at the onset of exercise in an asymptomatmic, self-referred adult population". CardinalScholar 1.0, 2010. http://liblink.bsu.edu/uhtbin/catkey/1567413.

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Purpose: Little is known about the heart rate (HR) responses at the onset of exercise, at peak exercise, and recovery in apparently healthy men and women. The purpose of this study was to determine the prevalence of abnormal HR acceleration at the onset of exercise, define the HR acceleration profile, determine if traditional cardiovascular disease (CVD) risk factors are associated with abnormal HR acceleration, and identify whether abnormal chronotropic responses cluster with abnormal HR acceleration in an asymptomatic, self-referred, adult population. Methods: A retrospective examination of a symptom-limited maximal treadmill test was performed for participants of a university-based fitness program between 1990 and 2006. Records were analyzed for various HR responses from individuals (N=947) of both sexes who represented a broad range of age and fitness levels (mean VO2: 32.9±9.4ml∙kg-1∙min-1). Abnormal HR acceleration at minute 1 and ⅓ total exercise time was defined as a HR increase from standing rest of ≤14 and ≤28 beats respectively. Results: The prevalence of abnormal HR acceleration at minute 1 and ⅓ total exercise time was 30.6% and 31.3% respectively. The mean HR increase during the first minute and ⅓ total exercise time was 20.5 ± 10.3 and 33.7 ± 10.4 beats respectively. Abnormal accelerators had a significantly better CVD risk factor profile (lower systolic and diastolic blood pressure, BMI, total cholesterol, triglycerides, higher VO2, and higher percent of regular exercise) than normal accelerators, despite consisting of a greater percentage of current smokers. Lastly, abnormal HR acceleration showed higher prevalence with abnormal HR recovery than with chronotropic incompetence. Conclusions: In the present study cohort, a lower HR increase at the onset of exercise was associated with a better CVD risk factor profile but the same differences were not seen at ⅓ total exercise time.
School of Physical Education, Sport, and Exercise Science

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27

Jim, Jin-to, i 詹展韜. "Genetics and molecular characterization of degenerative disc disease". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B35720189.

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28

Wong, Tik-wun Lina, i 黃荻媛. "Construction of an infectious PRRSV cDNA clone and its use as a vectorfor foreign gene expression". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44251841.

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29

Herman, Kazibwe. "Barriers experienced by parents/caregivers of children with clubfoot deformity attending specific clinics in Uganda". Thesis, University of the Western Cape, 2006. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_9901_1194348551.

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Clubfoot is the most common congenital structural deformity that leads to physical impairments in children in many poor developing countries. Inadequately treated or neglected clubfoot has been found to be a common cause of ohysical disability globally among children and young growing adults. Many children are referred to the clinics for treatment but some parents do not comply with the treatment regimen whcih requires attending for consecutive treatment sessions. The purpose of this study was to investigate barriers to treatment attendance parents/caregivers of children with clubfoot encounter in complying with clubfoot treatment during the plaster csting phase in Uganda.

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30

Sheehan, Susan. "Exploring the Genetics Regulating Kidney Function". Fogler Library, University of Maine, 2007. http://www.library.umaine.edu/theses/pdf/SheehanS2007.pdf.

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31

Purdum, Michael B. "The Effects of Positive Emotion, Negative Emotion, Flourishing, and Languishing on Cardiovascular Risk". Thesis, University of North Texas, 2010. https://digital.library.unt.edu/ark:/67531/metadc30503/.

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Positive psychology has led a movement that concentrates on positive characteristics. The current study examined the relationship between positive emotions, negative emotions, flourishing, languishing, and cardiovascular functioning. The study uses guided imagery to help participants recall a negative emotional event and positive emotional event in a counterbalanced order. The reverse order allowed us to examine the differential contributions of stress buffering versus facilitated recovery effects to higher levels of heart rate variability (HRV). The study also examined the relationship between mental health categories and known cardiovascular disease risk. Univariate analysis of variance revealed that positive emotions can serve as a stress buffer and dampen cardiovascular responses to a negative event. Also, analysis revealed a trend for the prediction that positive emotions can facilitate cardiovascular recovery following a negative event. Exploratory analysis did not reveal differences between a facilitated recovery group and a buffering group for cardiovascular measures. Future studies should include tighter control to help compare the differential influences of stress facilitation and stress buffering on cardiovascular functioning. The results from the study indicate that it is still too early to tell whether mental health buffers those individuals from developing CVD, and to answer whether languishing increases the risk of CVD. Longitudinal studies of young individuals without a prior history of any risk of CVD and who are flourishing or languishing might help provide answers to these questions.

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32

Masilamani, Twinkle Jasmine. "Identification of genetic markers associated with Marek's disease resistance in chickens". Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19691.

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Marek's disease (MD) is a highly contagious and economically important disease in the poultry industry. It is caused by an oncogenic avian herpes virus. The ability of the virus to evolve into new strains is a continual threat. Vaccination, proper management and genetic resistance are required to completely eliminate the pathogen. The discovery of several markers associated with MD resistance shows that genetic selection for resistance is feasible. Our objective was to identify markers in QTL regions that are associated with MD viraemia. The markers analysed were in the ODC gene, the GH gene and two chemokine genes, all of which are candidate genes for immune responsiveness. A database in a commercial strain of White Leghorn chickens was created. Heterozygous males and homozygous females were identified. The offspring were challenged with MD virus and spleen and thymus samples were collected six days after infection. The viral titre was quantified using competitive PCR. The data was analysed using non-parametric statistics. We found that the paternal alleles of a Hindlll RFLP in the ODC gene were associated with differences in MD viraemia in one of the six sire families analysed. In addition, a Sacl RFLP located in the GH gene also segregated for alleles, which affected MD viraemia. The analysis of the ODC gene was extended to include a second RFLP at a Msp\ site. Together with the Hindlll RFLP it defines three different haplotypes. One genotypic class AB (Hindlll (+/-), Mspl (+/+)) was associated with low vireamia in the thymus and the genotype BB (Hindlll (-/-), Mspl (+/+)) with high viraemia in the spleen. The result suggests that genetic variations in the ODC and GH gene affect MD viraemia. However, we cannot exclude that the observed effects might be due to linkage disequilibrium with adjacent genes. In the latter case, chromosome 3 and chromosome 1, which harbour the ODC and GH gene respectively, must segregate for regions that affect viraemia. The markers identified in this analysis can be used in marker assisted selection.

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33

Wilder, Steven P. "Computational analysis of susceptibility genes for diabetes and cardiovascular diseases in animal models". Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670109.

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Gudmundsdottir, Hafrun. "Coping strategies and causal attributions following myocardial infarction : a longitudinal study". Thesis, University of St Andrews, 1996. http://hdl.handle.net/10023/13534.

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Coping strategies and causal attributions have been shown to be related to recovery and adjustment following illness. Certain coping strategies and causal attributions, such as avoidant coping and other blame have been found to be related to higher levels of distress while others, like behavioural self blame and attention coping have been shown to be related to lower distress. There have however, been few longitudinal studies of the process. The study described here examined coping strategies, causal attributions and levels of distress over a period of 1 year in 91 patients following a first myocardial infarction (MI). Coping strategies (measured by the COPE), causal attributions (measured by open ended questions and a check-list) and distress (measured by the HAD a measure of anxiety and depression with minimal somatic symptoms), were measured within 2 weeks of discharge and at 2, 6 and 12 months post MI. The main findings of the study showed that both coping strategies and causal attributions changed over time. Patients were most likely to use attention coping strategies early following the illness onset but more avoidant and religious coping later on. Patients made fewer attributions as time passed and the most commonly reported causal attributions were stress and smoking. Results further revealed that both coping strategies and causal attributions were either concurrently related to and/or predictive of levels of distress. Avoidant coping was related to higher distress at all assessment times. Furthermore, both characterological self blame and other blame were found to be concurrently related to higher distress, with characterological self blame also being predictive of subsequent higher distress. These findings have implications for care and rehabilitation of cardiac patients as they imply that certain causal attributions and coping strategies might be problematic as regards post MI distress. This points towards the importance of examining and if necessary, altering certain causal attributions and coping strategies in order for the patient to gain the best possible recovery.

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35

Yuen, Man-fung, i 袁孟峰. "Role of hepatitis B virus genotypes B and C on chronic liver disease in the Chinese". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B33710089.

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Silver, Karlee Linnea. "Genotypic and phenotypic approaches to pathways involved in humoral autoimmunity". Thesis, University of Oxford, 2006. http://ora.ox.ac.uk/objects/uuid:1a18398f-942a-49a4-bd2e-a8ec4b4f647f.

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Lau, Hoi-lun, i 劉海倫. "Genetic and environmental determinants of bone mineral density in Southern Chinese". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31930633.

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Coe, Ellen Moster. "The correlation between changes in conicity index and changes in other risk factors for coronary heart disease at baseline and after a six- month intervention program". Virtual Press, 1995. http://liblink.bsu.edu/uhtbin/catkey/941352.

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The emphasis of the study was to determine the degree of correlation between the Conicity Index and known risk factors for heart disease. Conicity Index was shown in one study to be a useful screening tool in assessing the relationship between body composition and risk for heart disease. This study was designed to provide nutrition education and teach lifestyle modification to fourteen Veteran's Affairs patients. Change in specific risk factors including Waist-to-Hip Ratio, Body Mass Index, serum lipid levels and dietary intakes were correlated with change in Conicity Index over the six month study. Results from the present study did not suggest that the Conicity Index would serve as an effective screening tool for the present population. Mean body weight, body mass index, hip circumference, cholesterol and triglyceride levels, total caloric and fat intake all decreased significantly as a result of the program. Through nutrition education, behavior modification and group support, the risk for heart disease was successfully modified in this population.
Department of Family and Consumer Sciences

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39

Mells, George Frank Gannaway. "Investigation of the genetic basis of primary biliary cirrhosis : the PBC genetics study". Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648610.

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40

Williams, Kevin John. "Biological and genetic studies of wheat resistance to Heterodera avenae". Title page, summary and contents only, 1994. http://web4.library.adelaide.edu.au/theses/09PH/09phw7238.pdf.

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41

Hollis-Moffatt, Jade Elissa, i n/a. "Fine mapping and characterisation of an autoimmune diabetes locus, insulin dependent diabetes 21, (Idd21) on mouse chromosome-18". University of Otago. Department of Biochemistry, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070130.151657.

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Autoimmune disease is comprised of a wide variety of disorders characterised by a loss of self-tolerance towards a target organ or systemic region leading to its eventual destruction. Type 1 diabetes (T1D), autoimmune thyroid disease (AITD) and inflammatory bowel disease (IBD) are debilitating organ-specific disorders. These disorders arise from a combination of genetic factors and environmental triggers. A greater level of basic understanding of these disorders is required to delay and/or prevent their effects. Numerous autoimmune susceptibility loci have been implicated in the development of these disorders, but only a few causative genes have been identified. The aim of this project was to use comparative mapping between the human and mouse genomes to provide a greater understanding of the human autoimmune susceptibility locus, IDDM6, shown to be involved in a number of autoimmune disease conditions. Hall et al., (2003) previously demonstrated that the mouse autoimmune diabetes locus, Idd21, on distal mouse chr18 contains orthology to human IDDM6, IDDM10, IDDM18 and rat Iddm3. As part of this project the Idd21 locus was fine mapped using the congenic mapping technique. Beginning with the consomic mouse strain, NOD.ABHChr18 (90Mb of Biozzi/ABH-derived diabetes-resistant chr18 introgressed onto a non-obese diabetic (NOD) genetic background), 13 NOD.ABHIdd21 congenic mouse strains were established. The diabetes incidences of these congenic mouse strains were statistically compared stepwise along mouse chr18 and Idd21 was fine mapped to at least four independent autoimmune diabetes loci. Idd21.1 and Idd21.2 were located on distal mouse chr18 in regions orthologous to human IDDM6 and rat Iddm3 and Idd21.3a/b and Idd21.4 were located on proximal mouse chr18 in regions orthologous to human IDDM18 and IDDM10 respectively. Candidate genes of notable interest include Map3k8, Spink5, Cd14, Dcc, Smad4 and 7, Miz1, Nfatc1 and Cd226. Idd21.1 was further fine mapped. Beginning with the NOD.ABHD18Mit8-D18Mit214[(75-85.1Mb)] (Idd21.1) congenic strain (containing at least 10.1Mb of distal chr18 Biozzi/ABH diabetes-resistant DNA introgressed onto a NOD genetic background), seven subcongenic mouse strains were created. The diabetes incidence of these subcongenic mouse strains were statistically compared stepwise along mouse chr18 and Idd21.1 was fine mapped to at least three independent autoimmune diabetes loci; Idd21.11 (72.6-76.1Mb), Idd21.12a/b (75-76.1Mb and 80.6-81.4Mb) and Idd21.13 (84.8-85.1Mb). Candidate genes of interest in these regions include Dcc, Smad4 and 7, Miz1, Nfatc1, and Cd226. Functional characterisation of the Idd21.1 locus was performed by adoptively transferring splenocytes from female NOD or NOD.ABHIdd21.1 mice into cohorts of severe combined immune deficient (scid) female mice, NOD/LtSz.Prkdc[scid] and NOD/LtSz.Prkdc[scid].ABHIdd21.1. There were two notable findings from this work. Firstly, NOD.ABHIdd21.1 splenocytes are not as effective as NOD at transferring diabetes to either NOD/LtSz.Prkdc[scid] (P = 0.0004) or NOD/LtSz.Prkdc[scid].ABHIdd21.1 (P = 0.0178), suggesting that Idd21.1 acquired immune cells are not as diabetogenic as NOD. Secondly, NOD/LtSz.Prkdc[scid].ABHIdd21.1 mice are more resistant to autoimmune attack than NOD/LtSz.Prkdc[scid] when injected with either NOD (P = 0.0015) or NOD.ABHIdd21.1 splenocytes (P = 0.0014), suggesting that Idd21.1 either acts by altering the intrinsic resistance of beta-cells to autoimmune attack or due to changes in the innate immune system. Other NOD-based models of autoimmune disease, spontaneous and experimental autoimmune thyroiditis and spontaneous colitis, were also investigated to determine whether Idd21.1 is a common autoimmune disease locus. When bred onto the NOD.Cg-H2[h4] (thyroiditis model) genetic background Idd21.1 was demonstrated to increase the development of thyroiditis and reduce the incidence of insulitis in spontaneous (untreated) but not experimental (NaI-induced) NOD.Cg-H2[h4] mice. When bred onto the NOD.Cg-Il10[tm1Cgn] (colitis) genetic background Idd21.1 was demonstrated to inhibit the development of rectal prolapse in breeding female NOD.Cg-Il10[tm1Cgn] mice. Data from this thesis demonstrate that the IDDM6 orthologous region in mouse, Idd21.1, contains several loci that influence autoimmune diabetes, thyroiditis and colitis in NOD-based mouse models. These findings are consistent with previous knowledge that IDDM6 is a common autoimmune susceptibility locus.

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42

Zhu, Quan. "Role of CDP in MMTV transcriptional regulation and tumorigenesis". Access restricted to users with UT Austin EID, 2001. http://wwwlib.umi.com/cr/utexas/fullcit?p3037038.

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Hill, John Stuart. "Genetic and environmental factors affecting the incidence of coronary artery disease in heterozygous familial hypercholesterolemia". Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/28810.

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Familial hypercholesterolemia (FH) is an autosomal dominant disorder in which the primary defect is a mutation in the LDL receptor. Heterozygous FH is among the most common inborn errors of metabolism and remains as the best example of an inherited defect causing premature coronary artery disease (CAD). This thesis describes the physical and biochemical characteristics of heterozygous FH in a large cohort consisting of 208 women and 156 men. The influence of both genetic and environmental factors on the clinical expression of FH were investigated to better understand the phenotypic variation within FH and thus improve the prediction and treatment of CAD in affected individuals. The general incidence of CAD in this population was lower compared to previous reports but the differences between the sexes were expected. It was shown that men had a much higher frequency of CAD (31%) compared to women (13%) despite having lower concentrations of total and LDL cholesterol. In addition, the average age of onset of coronary symptoms was delayed in females, 55 years compared to 48 years for males. A greater risk of developing CAD for men was associated with low levels of HDL cholesterol and a history of smoking. In women, however, CAD was associated with elevated triglyceride levels and the presence of hypertension. In order to efficiently assess the influence of the co-inheritance of the apolipoprotein E polymorphism in this large FH population, a novel apo E phenotyping procedure was developed. Phenotypes were determined directly from plasma which was neuraminidase treated, delipidated and focused in polyacrylamide minigels. The accuracy of this method was confirmed by making a comparison to the established procedure of phenotyping by isoelectric focusing of delipidated VLDL. The low cost, speed and simplicity of the minigel methodology provided ideal conditions to phenotype a large patient population. The frequencies of the ɛ2, ɛ3 and ɛ4 alleles of apolipoprotein E in 125 unrelated FH subjects did not differ significantly from the normal population. In addition, there was no apparent relationship between apo E4 and the concentration of any of the parameters in the plasma lipid profile. However, the presence of the E2 isoform was associated with significantly elevated triglycerides in both sexes. From this study, it is evident that the mutant FH gene exerts its effect within a system of interacting environmental and polygenic factors that are known to modify atherosclerotic risk. It has been established that the dissimilarity in the frequency of CAD between men and women is related to differences between the impact of known risk factors and the incidence of CAD. Therefore, the importance of the influence of these risk factors and the differences between men and women should be emphasized when treating and predicting the development of CAD in patients with FH.
Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

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44

Li, Yick-yeung, i 李亦揚. "Molecular and phylogenetic analysis of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2(PCV2)". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29297102.

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李震威 i Chun-wai Davy Lee. "RET receptor tyrosine kinase in developing, adult and polycystic kidneys". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31241931.

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46

Tse, Wing-on, i 謝永安. "Hepatic oxidative stress in COX-1 knockout mice". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B4501095X.

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Lai, Josanna Yuk-Lin. "Is keeping in or letting out anger good for your heart?" Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/30099.

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Given the presumed importance of cardiovascular reactivity and the role of anger in the development of hypertension and coronary heart disease, this study is the first to jointly examine three related areas (i.e. gender effects, anger direction preference, and opportunity/no opportunity to aggress following an anger Inducing situation). The present study tested the following hypotheses: a) that cardiovascular reactivity would vary as a function of subjects' gender and direction preference; b) that the rate of cardiovascular recovery would vary as a function of anger direction preference and opportunity/no opportunity to aggress; c) that the subjective feelings of anger after harassment would vary as a function of gender, anger direction preference, and opportunity/no opportunity to aggress; and d) that the evaluation of experimenter's competency and performance would vary as a function of anger preference. 56 females and 49 males executed a math task while being harassed for "poor performance". Next, they were randomly assigned to either write a negative evaluation of the frustrator or to copy a neutral paragraph and then to circle some letters in another paragraph. Heart rate and blood pressure were measured intermittently throughout. Subjects' preferred mode of anger expression (i.e. anger-in versus anger-out) had been previously assessed and cross validated by self as well as peer evaluations. Results indicated that gender was a better predictor than anger direction preference for cardiovascular reactivity to harassment. Complex patterns of recovery were detected with Intriguing sex differences. Results on male diastolic recovery were consistent with a matching hypothesis of anger direction preference but only for anger-out males. In addition, subjective anger for males was related to opportunity/no opportunity conditions, whereas females did not show such a relationship. Female anger-ln's showed quicker systolic recovery than anger-out's. Lastly, the evaluation of experimenter's competency and performance did not vary as a function of anger preference. Therapeutic implications of the findings within the context of anger control as well as trends for future research are discussed.
Arts, Faculty of
Psychology, Department of
Graduate

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48

Agenbag, Gloudi. "Molecular genetic analysis of familial breast cancer in South Africa". Thesis, Link to the online version, 2005. http://hdl.handle.net/10019/953.

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Lam, To-kam, i 林吐金. "In vivo study of asporin polymorphic variants in chondrogenesis and degenerative disc disease (DDD)". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42182591.

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Ross, Ian Lindsay. "Mechanisms of biocontrol of Gaeumannomyces graminis var. tritici by Pseudomonas corrugata strain 2140 : genetic and biochemical aspects". Title page, table of contents and summary only, 1996. http://web4.library.adelaide.edu.au/theses/09PH/09phr824.pdf.

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Bibliography: leaves 207-220. Pseudomonas corrigata strain 2140 (Pc2140), isolated from wheat field soil in Australia, antagonises the take-all fungus, Gaeumannomyces graminis var. tritici (Ggt) in vitro and significantly reduces take-all symptoms on wheat in pot trials. This study investigates the mechanisms by which the biocontrol agent reduces the disease symptoms. Biochemical analysis of metabolites of P. corrugata 2140 reveal a number of compounds potentially antagonistic to Ggt and which may play a role in disease control. These include water-soluble antibiotics, siderophores, proteases, peptides and volatiles including hydrogen cyanide.

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