Blackleg is a disease of canola and rapeseed cultivars that is caused by the fungus Leptosphaeria maculans (Desm.) Ces. & de Not., and it is by far the most destructive pathogen of canola in North America. In recent years, blackleg strains belonging to pathogenicity groups (PG) 3 and 4 have been discovered in North Dakota. Recent outbreaks of the disease have added a sense of urgency to characterize the risk these new strains represent for the canola industry and to identify sources of resistance against them. Thus, the objectives of this study were to screen germplasm collections of Brassica rapa, B. napus. and B. juncea for their reaction to PG3 and PG4 and to evaluate the reaction of a sample of currently used canola commercial cultivars grown in North Dakota to PG3 and PG4 as means to estimate the risk these new strains represent. All canola germplasm and commercial cultivars were evaluated in replicated trials in greenhouse conditions using cotyledon bioassays. In 2009 and 2010, the effect of these strains, using five inoculation sequences, on the reaction of canola seedlings was also evaluated. Field trials were not conducted because of the limited geographical distribution of the new strains. No adequate sources of resistance were identified among the 277 B. rapa and 130 B. napus accessions evaluated; however, 22 of the 406 accessions of Brassicajuncea evaluated were considered to have moderate levels of resistance. B. juncea seedlings that survived these inoculations were self-pollinated and their progeny (F1) were also screened. As before, surviving seedlings were self-pollinated. These F2 seeds are the elite materials that could be used in future breeding programs. The complementary study evaluating the role of sequence inoculations in reaction of canola seedlings to blackleg indicated that an increased susceptibility to PG3 occurred when seedlings were first inoculated with PG4; however, reaction to PG4 was not enhanced by a prior inoculation with PG3. All 75 commercial cultivars evaluated were susceptible to PG3 and PG4, indicating that the risk these new strains represent to the canola industry of the region is serious. Further, when a subsample of 16 cultivars were challenged with PG2, they were either resistant or moderately resistant, suggesting the ratings the industry are using relate to reaction of those cultivars to PG2 but not to the new strains; thus, growers should use caution when using these ratings while deciding on which cultivars to plant. / North Dakota State University. Department of Plant Pathology / USDA North Central Canola Research Program / Northern Canola Growers Association

Tan spot, caused by Pyrenophora tritici-repentis (Ptr), is a major foliar disease on wheat. The pathosystem involves three pairs of necrotrophic effector (NE) and host sensitivity (S) gene interactions, namely Ptr ToxA-Tsn1, Ptr ToxB-Tsc2 and Ptr ToxC-Tsc1. Additionally, genetic factors conferring race-nonspecific resistance have been identified. The objectives of this study were to map tan spot resistance QTL and investigate the role of NE-S interactions in disease in durum using association and bi-parental mapping. Evaluation of a worldwide collection of durum accessions allowed identifying highly resistant nineteen lines to multiple Ptr races. Association mapping revealed genomic regions on chromosomes 1A, 2B and 3B significantly associated with resistance to tan spot, which likely correspond to Tsc1, Tsc2 and racenonspecific resistance. Using a bi-parental population derived from Ben and PI 41025, we found that ToxA-Tsn1 interaction plays no significant role in disease, instead a major race-nonspecific QTL on chromosome 5A was identified.

Soybean mosaic virus (SMV), a potyvirus detected worldwide, can cause serious diseases in soybean (Glycine max L. Merr.). Host resistance to SMV conferred by a single dominant gene, Rsvl, was studied as a model to gain insights of plant virus resistance genes, and to facilitate the breeding of resistant cultivars. DNA restriction fragment length polymorphisms (RFLPs) and microsatellites (or simple sequence repeats, SSRs) were used as genetic markers to identify the chromosomal location of Rsvl1 in a cross between PI 96983 (resistant) and a susceptible cultivar. Twenty five RFLP and three SSR loci polymorphic between the parental lines were analyzed in 107 F, individuals. Genotypes of Rsv1 were determined by inoculating F2.3 progeny with SMV-G1. Genetic analysis revealed that one SSR (HSP176L) and two RFLP (pA186 and pK644a) markers are closely linked to Rsv1, with a distance of 0.5, 1.5, and 2.1 cM, respectively. The tight linkages of the three markers to Rsv1 were confirmed by SSR and RFLP analysis of three near isogenic lines (NILs) of Rsv1 derived from PI 96983 or Marshall. The three Rsv1-linked markers were then used to screen 67 diverse soybean types. These marker loci showed a remarkably high level of polymorphism, indicating a possible association between disease resistance and rapid sequence divergence. At each Rsv1-linked marker locus, one SSR allele or RFLP haplotype is highly correlated with SMV resistance. These resistance markers, especially the SSR allele at HSP176L which can be detected by the polymerase chain reaction (PCR), may be useful for germplasm screening. The grouping of the 67 accessions according to their Rsv1-linked multilocus marker haplotypes agrees with available pedigree information. A set of differential cultivars known to contain Rsv1 clustered into putative Rsv1- carrying groups. Based on molecular marker analysis and previous inheritance studies, 37 of the 45 resistance accessions probably derive their resistance from Rsv1. The remaining eight accessions include Columbia (Rsv3), and the other potentially diverse resistance sources. A heat shock protein (HSP) multigene family, HSP176L included, was analyzed for its positional proximity to the Rsv1 gene cluster. A technique termed amplified sequence length polymorphism (ASLP) was developed to convert known DNA sequences to PCR-based genetic markers. Among six pairs of HSP primers used, two (HSP175E and 185C) detected ASLPs between the parents, and segregated in the F₂ population with a size of 174. HSP175E was found to be closely-linked (0.7 cM) to HSP176L, both of which are Class I small HSP genes. HSP185C, however, was mapped to a different linkage group, suggesting that it may belong to another family. ADR11, a member of auxin down-regulated (ADR) multigene family, is known to be linked to HSP173B, also a Class I gene but not mappable in this population. ASLP analysis of ADR11 in a set of Rsv1 NILs indicates that it is linked to Rsv1, and ADR11 co-segregates with HSP175E in the F, population. Thus, the Class I small HSP multigene family including HSP176L, 175E, and 173B, and possibly a family of ADR genes, is located near the Rsvi resistance gene cluster. / Ph. D.

[Truncated abstract] Asthma genetic studies have identified many genes that contribute to the pathogenesis of asthma and related variables. Members of the secretoglobin family appear to play an important role in controlling airway inflammation but they have received relatively little attention in asthma genetic research. In this thesis, I have investigated the genes of two members of the secretoglobin family (16 kDa Clara cell secretory protein (CC16) and secretoglobin 3A2 (SCGB3A2)) that are expressed at high levels in the airways and are important anti-inflammatory agents. The overall aim of these studies was to investigate the genetic variability of the CC16 and SCGB3A2 genes and their influence on airway inflammatory disease. The main hypothesis was that genetic variability in the genes for CC16 and SCGB3A2 exert an influence on airway inflammatory disease. Three populations were investigated: (1) a paediatric case control population (n=99), (2) an unselected birth cohort followed longitudinally at ages 1 month (n=244), six (n=123) and 11 years (n=195) and (3) an unselected Aboriginal Australian population (n=251). The case-control population was screened for novel DNA sequence variants in the CC16 promoter and the SCGB3A2 5’UTR and exons. No novel sequence variants were identified in the CC16 promoter and two were identified in the SCGB3A2 5’UTR (G- 811A and G-205A). A single nucleotide polymorphism previously identified in the CC16 gene (A38G) and the two polymorphisms identified in the SCGB3A2 gene were genotyped in both unselected populations. Genotype/phenotype associations were identified with adjustment for potential confounders such as age, gender, height and maternal tobacco smoking, where appropriate. This was due to the contribution of these factors to the aetiology of asthma, atopy and related phenotypes. All three polymorphism frequencies were significantly different between these two ethnically diverse populations

Dissertation (PhD(Agric))--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: This study was carried out to investigate whether environmental and/or genetic factors had an effect on the incidence of epistaxis related to exercise-induced pulmonary haemorrhage among racehorses in Southern Africa. A further aim was to estimate the heritability of liability to epistaxis in the Southern African Thoroughbred population. For the purpose of the environmental study, the data covering the period 1986-2001 and involving a total of778 532-race runs, were analysed. This included the following race start information: date of race (day/month/year), age, sex, breeder, trainer, distance, jockey, state of going, weight carried, centre of racing and altitude. The genetic part of the data was two-fold in nature and included firstly the analysis of all horses that suffered epistaxis whilst racing in Southern Africa from 1986 to 2001 and involving 1118 individual bleeders. The second genetic analysis included the same Southern African population plus those Southern African horses exported to Mauritius and then being recorded as bleeders in that country (1252 bleeders in total). Pedigree data covering the period 1960-1986 was used as required to calculate the incidence of bleeding amongst ancestors of the post 1986 era. Only pedigrees of horses that raced were included in this study as it was not possible to predict whether non-runners would have bled had they raced. Consequently all non-runners and also those that raced overseas in countries where bleeding occurrence was not recorded were excluded. Veterinarians employed by the Jockey Club suspended officially recorded horses that showed epistaxis as demonstrated by frank bleeding from the nostrils after racing. Oncourse endoscopy is not employed as a routine on any of the Southern African racetracks. In the environmental study epistaxis was identified in 1 287 race starts (0.165%). Epistaxis related to exercise-induced pulmonary haemorrhage was significantly (p<0.001) associated with altitude, age, race year, month and the day of racing. More horses demonstrated epistaxis at sea level than at altitude, between the months of May - October than the rest of the year, in older horses than in horses less than three-years old, after 1995 than between the years 1986 and 1995, and on Fridays and Sundays than on any other week day. No association could be established between epistaxis and breeder, trainer, distance, jockey, state of going, sex and weight carried. The heritability of liability method as described by Falconer (1989) was used to estimate the relative importance of heredity and environment. For the period investigated, the population incidence for epistaxis in Southern African horses was 2.1%. The estimation of heritability ofliability showed that first-degree relatives had a figure of 55.4%. The heritability of second- and third degree relatives were 41.3% and 30.4% respectively. The data investigated depicts horses that bled almost exclusively on race days as only a small percentage (- 5%) was reported as having bled during exercise. Accordingly, the full extent of epistaxis amongst racing Thoroughbreds in Southern Africa is difficult to gauge. Pedigree and race run data from Thoroughbreds racing in Southern Africa, covering the period 1986-2002 (63 146) horses in pedigree data-set and 778 532 race runs, were further analysed in order to study genetic and environmental factors affecting the incidence of epistaxis as associated with EIPH (exercise-induced pulmonary haemorrhage). As fixed effects for the model, variables that were tested significantly in a preliminary data analyses, were included. Various combinations of such variables namely age, weight, altitude, sex, month and going were tested. Fixed effects that were included in the fmal model were gender, going and altitude. The heritability estimates from a logit transformed analysis for epistaxis fitting both the animal and sire generalized mixed models were 0.23 and 0.40 respectively, which indicated that epistaxis as associated with EIPH in the Southern African Thoroughbred sires has a strong genetic basis. Genetic trends indicating an increase in epistaxis were also found. It is concluded that the frequency of epistaxis related to pulmonary haemorrhage is associated with altitude, winter and spring months and the horse's age. It is suggested that racing at a lower altitude may increase the probability of exercise-induced pulmonary haemorrhage. It is clear that epistaxis in the racing Thoroughbred has a strong genetic basis. It is further suggested that horses showing frank bleeding from the nostrils after racing or exercise, be suspended and not used for breeding purposes. This would result in relatively fast progress being made towards eradicating this costly scourge of the modem Thoroughbred racehorse. Affected stallions and those racing whilst being treated with furosemide, should be barred from breeding and not be considered as future sires. Estimated breeding values for epistaxis should be used as a tool for selecting against it and be considered in breeding programmes to decrease the incidence thereof. / AFRIKAANSE OPSOMMING: 'n GENETIESE ANALISE VAN DIE VOORKOMS VAN LONGBLOEDING IN DIE SUID-AFRIKAANSE RENPERD: Die doel met hierdie studie was om vas te stelof omgewings- of genetiese faktore enige invloed op die voorkoms van longbloeding in die Suid-Afrikaanse renperd het. 'n Verdere doelstelling was om die oorerflikheid op die onderliggende verspreiding van longbloeding in die Suid-Afrikaanse Volbloedpopulasie te bepaal. Vir die omgewingstudie is data wat oor die periode 1986-2001 strek en wat 'n totaal van 778 532 wedren-deelnames ingesluit het, statisties ondersoek. Die data het die volgende inligting ingesluit: datum van deelname, ouderdom, geslag, teler, afrigter, afstand van wedren, jokkie, toestand van baanoppervlakte, gewig gedra, sentrum waar deelname plaasgevind het en die hoogte bo seespieël van die sentrum. Die studie van die genetiese aspekte het eerstens 'n analise van al die perde wat longbloeding tydens 'n wedren in Suider-Afrika gedurende die jare 1986-2002 ondervind het (I118 perde), en tweedens dieselfde populasie perde, plus die Suiderlike-Afrikaanse perde wat uitgevoer is na Mauritius en bloeding daar ondervind het, (1252 perde), ingesluit. Ter aanvulling is uitgebreide stamboomdata van voorouers gedurende 1960-1986 gebruik om die voorkoms van longbloeding tydens die post 1986 tydvak te bepaal. Slegs stambome van renperde wat aktief aan renne deelgeneem het, is in die data ingesluit aangesien dit nie moontlik was om te voorspel of 'n perd wat nooit aan wedrenne deelgeneem het nie, longbloeding sou ondervind indien dit wel deelgeneem het. Dus is alle renperde wat nooit aan wedrenne deelgeneem het, asook daardie perde wat in die buiteland deelgeneem en waar longbloeding nie aangeteken word nie, uitgesluit. Alle perde wat bloeding van die neus na wedrenne getoon het, is deur veeartse in diens van die Jokkie Klub van Suid-Afrika ondersoek, as 'n bloeier aangeteken en van verdere deelname aan wedrenne geskors. Endoskopie word op geen van die Suid- Afrikaanse renbane as 'n standaard praktyk na wedrenne uitgevoer nie. Longbloeding het in 1 287 perde of gedurende 0.165% van alle wedrenne plaasgevind. Longbloeding soos geassossieer met EIPH, (exercise-induced pulmonary haemorrhage), is betekenisvol (p<0.001) met hoogte bo seespieël, ouderdom, dag van deelname, maand, en jaar verbind. Meer perde het longbloeding by seevlak in vergelyking met hoër vlakke bo seespieël ondervind, tussen die maande Mei-Oktober as die res van die jaar, in perde ouer as drie-jaar, na 1995 as tussen die jare 1986-1995, op Vrydae en Sondae as enige ander dag van die week. en meer by reuns as by merries of hingste. Geen verwantskap kon tussen bloeding en teler, afrigter, afstand, jokkie, toestand van baan, geslag en gewig gedra, gevind word nie. Die oorerflikheid op die onderliggende verspreiding vir longbloeding soos omskryf deur Falconer (1989), is gebruik om die relatiewe belangrikheid van oorerflikheid en omgewing te bepaal. Vir die periode bestudeer, was die voorkoms van longbloeding in die Suid-Afrikaanse renperd 2.1%. Die oorerflikheid van longbloeding was 55.4% vir eerste-graadse verwantes. By tweede-graadse verwantes was die ooretlikheid 41.3% en by derde-graadse verwantes 30.4%. Die data wat ondersoek is, was bykans uitsluitlik die van perde wat tydens wedrenne gebloei het en slegs 'n baie klein persentasie (~ 5%) was aangeteken as perde wat tydens oefening gebloei het. Dus is die volle omvang van longbloeding in Suider-Afrikaanse Volbloedperde moeilik om akkuraat te bepaal. Die stamboom- en wedrendata van Suid-Afrikaanse Volbloedperde is verder ontleed in 'n poging om die genetiese en omgewingsfaktore se invloed op die voorkoms van longbloeding, soos geassosieer met EIPH te bepaal. As vaste effekte vir die model is veranderlikes wat betekenisvol gevind was, ingesluit. Verskeie kombinasies van hierdie veranderlikes soos ouderdom, gewig, hoogte bo seespieël, geslag, maand en toestand van die baan is ingesluit. Die vaste effekte wat in die finale model ingesluit is, was geslag, toestand van die baan en hoogte bo seespieël. Die beraamde oorerflikheid verkry vanaf 'n "logit" getransformeerde analise vir longbloeding wat beide die diere- en vader- gemengde model gepas het, was onderskeidelik 0.23 en 0.40, wat 'n aanduidending is dat longbloeding, soos geassosieer met ElPH, 'n sterk genetiese grondslag het. Genetiese tendense het ook gedui op 'n toename in die voorkoms van longbloeding, veraloor die laaste vyf jaar van die studie. Samevattend is die bevinding dat die frekwensie van longbloeding 'n betekenisvolle verwantskap toon met hoogte bo seespieël, winter en lente maande en die perd se ouderdom. Dit word voorgestel dat renperde wat deelneem aan wedrenne by laer vlakke van hoogte bo seespieël, meer onderhewig aan longbloeding sal wees. Uit die resultate verkry is dit duidelik dat longbloeding 'n genetiese grondslag het. Dit word voorgestel dat perde wat fisiese simptome van neusbloeding na of gedurende wedrenne toon, geskors word van verdere deelname en ook nie toegelaat word om mee te teel nie. Hierdie maatreëls behoort aanleiding te gee dat relatief vinnige vordering gemaak sal word in die strewe om hierdie ongewenste sindroom in die moderne Volbloed te verminder. Aangetaste hingste, asook die wat aan wedrenne deelgeneem het terwyl hul behandeling ontvang met furosemide, moet nie toegelaat word om te teel en nie as toekomstige teelhingste oorweeg word nie. Die waarde van voorspelde teelwaardes vir longbloeding moet nie onderskat word in seleksie daarteen nie en moet in teelprogamme om die voorkoms daarvan te verminder, oorweeg word.

Thesis (PhD (Genetics))--University of Stellenbosch, 2010. / Includes bibliography. / ENGLISH ABSTRACT: The wild relatives are an important source of new genes for the genetic improvement of wheat. At Stellenbosch University the leaf and stripe rust resistance genes Lr54 and Yr37 were transferred from Aegilops kotschyi to chromosome 2DL of wheat. In an attempt to reduce the size of the whole-arm translocation on which the resistance genes occur, homoeologous pairing was induced between the wheat and corresponding Ae. kotschyi chromatin. The purpose of this study was to: (i) Evaluate the testcross progeny thus obtained; identify translocation recombinants that retained Lr54/Yr37 and to characterize these using molecular markers (ii) Test for the presence of genes for photoperiod insensitivity (Ppd) and reduced height (Rht) believed to be associated with the translocation (iii) Develop a SCAR marker for the most useful recombinant that could be recovered. Ten putative translocation recombinants were identified following the screening of 159 hemizygous testcross F1 plants with three microsatellite markers specific for chromosome arm 2DL. The recombinants were then characterized with another five microsatellite markers. Using the eight microsatellite markers the recombinants were ordered in two size categories with recombinant #74 being the shortest and having retained only proximal alien chromatin on 2DL. In addition to microsatellite markers, RAPDs, RGAs, AFLPs and SCAR markers were genetically mapped to the translocation and further resolved the recombinants into three size categories. In an attempt to find suitable markers linked to the shortest recombinant (#74) a polymorphic 410 bp AFLP fragment produced with the enzyme/selective nucleotide combination EcoRI – AAC/MseI – CAT, was converted into a dominant SCAR marker. In addition three microsatellite markers that mapped to recombinant #74 provided a useful recessive molecular marker system to detect Lr54/Yr37. Evaluation of the 10 recombinants with four 2DS-specific microsatellite markers revealed a large deletion of this chromosome arm in recombinant #74. This deletion may affect plant phenotypic characteristics and a strategy to replace the deleted region in recombinant #74 is proposed. To test for the presence of a gene for photoperiod insensitivity on the translocation, translocation-carriers plus controls were subjected to long and short day treatments, and the effect on time to flowering was studied. However, no evidence was found for the presence of such a gene. A height experiment to test for the presence of an Rht gene on the translocation confirmed its presence. This gene (designated H) appeared to be different from Rht8 on chromosome 2DS and was mapped on 2DL. While H does not occur in a chromosome region that corresponds with the location of Rht8, it does not rule out the possibility that they could be orthologous loci. Plant height data obtained for recombinant #74 suggested that H was lost through recombination in this particular recombinant. A greenhouse experiment suggested that the full-length translocation increased 100 kernel mass but had a detrimental effect on overall plant yield. Since a much shorter recombinant (#74) has been obtained, this will also have to be evaluated for associated effects. Such an evaluation needs to be done under commercial growing conditions and should involve the comparison of near-isogenic bulks with and without recombinant chromosome #74. The stripe rust resistance gene (Yr37) was mapped by screening hemizygous TF2 progeny of the 10 recombinants with Puccinia striiformis pathotype 6E22A+. Recombinant #74 retained both Lr54 and Yr37 and the two genes therefore occur towards the centromere. / AFRIKAANSE OPSOMMING: Wilde verwante spesies is ‘n belangrike bron van nuwe gene vir die genetiese verbetering van koring. By die Universiteit van Stellenbosch is die blaar-roes en streep-roes weerstandsgene Lr54 en Yr37 vanaf Aegilops kotschyi na chromosoom 2DL van koring oorgedra. ‘n Poging is vervolgens aangewend om die vol-armtranslokasie waarop die weerstandsgene voorkom te verklein deur homoeoloë paring tussen die koring en ooreenstemmende Ae. kotschyi chromatien te induseer. Die doelstelling van hierdie studie was daarom as volg: (a) Evaluering van die verkreë toetskruis-nageslag asook die identifisering en karakterisering van translokasie rekombinante wat Lr54/Yr37 behou het. (b) Toetsing vir fotoperiode onsensitiwiteits- (Ppd) en verkorte plant-hoogte (Rht) gene wat moontlik op die translokasie kon voorkom. (c) Die ontwikkeling van ‘n volgorde-spesifieke polimerase kettingreaksie (PKR) vir die mees bruikbare rekombinant. Tien translokasie rekombinante is geïdentifiseer nadat 159 hemisigotiese toetskruis F1-plante met drie mikrosatelliet-merkers, spesifiek vir chromosoom-arm 2DL, ge-evalueer is. Die rekombinante is hierna met vyf verdere mikrosatellietmerkers getoets. Die data van die agt mikrosatelliet-loci het die rekombinante in twee grootte-kategorieë geplaas waarvan rekombinant #74 die kortste was met slegs die proksimale gedeelte van 2DL wat uit vreemde chromatien bestaan. Behalwe mikrosatellite-merkers is toevallig-geamplifiseerde polimorfiese DNS (RAPD), weerstandsgeen-analoog (RGA), geamplifiseerde volgordelengte polimorfisme (AFLP) en volgorde-gekarakteriseerde geamplifiseerde-streke (SCAR) merkers ook geneties op die translokasie gekarteer. Data van die addisionele merkers het dit moontlik gemaak om die rekombinante in drie grootte-kategorieë te skei. Pogings om ‘n merker vir die kortse rekombinant (#74) te vind, het gelei tot die omskakeling van ‘n 410 bp polimorfiese AFLP-fragment (geproduseer met die ensiem/selektiewenukleotied kombinasie EcoRI - AAC/MseI - CAT), na ‘n dominante, volgordespesifieke PKR-merker. Hierbenewens kan drie mikrosatelliet-merkers wat op rekombinant #74 karteer as resessiewe merkers vir die identifisering van Lr54/Yr37 gebruik word. Die evaluering van die 10 rekombinante met vier chromosoom 2DSspesifieke mikrosatelliet-merkers het ‘n groot delesie van chromosoom-arm 2DS in rekombinant #74 uitgewys. Die delesie mag plant fenotipiese kenmerke beïnvloed en daarom is ‘n strategie vir die vervanging daarvan in rekombinant #74 voorgestel. Ten einde te toets of ‘n geen vir fotoperiode-onsensitiwiteit op die translokaie voorkom is translokasie-draers en kontroles aan lang- en kortdag-behandelings onderwerp en is die effek hiervan op dae-tot-blom gemeet. Geen bewyse vir so ‘n geen kon gevind word nie. ‘n Hoogte-eksperiment om te toets vir die teenwoordigheid van ‘n Rht-geen op die translokasie, het bevestig dat so ‘n geen wel voorkom. Die geen (voorgestelde simbool H) is gekarteer op 2DL en verskil oënskynlik van Rht8 op chromosoom 2DS. Die verskillende chromosoom-ligging van H en Rht8 skakel egter nie die moontlikheid dat hulle ortoloë loci mag wees uit nie. Plant-hoogte data vir rekombinant #74 het daarop gedui dat H nie meer in hierdie rekombinant voorkom nie. Data van ‘n glashuis-eksperiment het daarop gedui dat die vollengte-translokasie 100-korrel-massa verhoog maar dat dit plant-opbrengs verlaag. Aangesien ‘n aansienlike korter rekombinant (#74) verkry is, sal dit ook vir gekoppelde effekte getoets moet word. So ‘n evaluering moet egter onder kommersiële toestande gedoen word met gebruik van naby isogeniese-lyne met en sonder rekombinante chromosoom #74. Die streep-roes weerstandgeen (Yr37) is gekarteer deur hemisigotiese TF2- nageslag van die 10 rekombinante te toets vir weerstand teen Puccinia striiformis patotipe 6E22A+. Rekombinant #74 het beide Lr54 en Yr37 behou en die twee gene karteer dus naby die sentromeer.

Significant alterations in the environmental conditions can have pronounced effects on plant genome stability. Recent evidence argues for a global involvement of the components of epigenetic modules in the regulation of genome homeostasis both immediately after stress exposure and long after environmental cues were acquired. The last observation is of particular interest as the memory of imposing stress can be maintained at the molecular level throughout plant ontogenesis and may be faithfully propagated into the following generation. Our study provides evidence that epigenetic repercussions exerted by stress exposure of parental plants manifest themselves in untreated progeny at all three levels of the epigenetic module: DNA methylation, histone posttranslational modifications and small RNA metabolism. Additionally, the results of our study shed new light on the engagement of the epigenetic machinery in the maintenance of plant genome integrity by counteracting the activity of invading nucleic acids. / xv, 280 leaves : ill. ; 29 cm

Sy, Hing Yee. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves lxxiv-xciv). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; appendixes I-III in Chinese.

Cheung Hoi Hung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 151-166). / Abstracts in English and Chinese. / ACKNOWLEDGEMENT --- p.I / ABSTRACT --- p.II / ABBREVIATIONS --- p.IV / LIST OF FIGURES --- p.VII / LIST OF TABLES --- p.IX / CONTENTS --- p.X / Chapter CHAPTER ONE: --- GENERAL INTRODUCTION / Chapter 1.1 --- Non-coding RNAs in transcriptional output --- p.2 / Chapter 1.2 --- Diverse functions of non-coding RNAs --- p.5 / Chapter 1.3 --- HI9: imprinted non-coding RNA --- p.6 / Chapter 1.4 --- Objective --- p.7 / Chapter CHAPTER TWO: --- The ROLE OF H19 RNA IN MDR1 EXPRESSION OF HUMAN HEPATOCELLULAR CARCINOMA HepG2 CELLS / Chapter 2.1 --- Introduction / Chapter 2.1.1 --- H19-Igf2 locus as a model for genomic imprinting --- p.10 / Chapter 2.1.2 --- HI9 as a non-protein coding regulatory RNA --- p.12 / Chapter 2.1.3 --- Controversial roles of H19 RNA --- p.13 / Chapter 2.1.4 --- Novel role of H19 RNA in drug resistance --- p.15 / Chapter 2.2 --- Materials and methods / Chapter 2.2.1 --- Materials --- p.17 / Chapter 2.2.2 --- Methods / Chapter 2.2.2.1 --- Cell culture --- p.19 / Chapter 2.2.2.2 --- Plasmid construction and stable cell transfection --- p.19 / Chapter 2.2.2.3 --- Transient gene transfection --- p.20 / Chapter 2.2.2.4 --- RNA isolation and RT-PCR --- p.21 / Chapter 2.2.2.5 --- MTT drug sensitivity assay --- p.22 / Chapter 2.2.2.6 --- Western blot analysis --- p.22 / Chapter 2.3 --- Results / Chapter 2.3.1 --- Differential expression of H19 RNA in different human cancer cell lines --- p.24 / Chapter 2.3.2 --- R-HepG2 cells over-expressed P-glycoprotein and H19 RNA --- p.24 / Chapter 2.3.3 --- Development of H19-silenced cell lines in HepG2 cells by RNA interference --- p.26 / Chapter 2.3.4 --- Altered drug sensitivity in H19-silenced cells --- p.28 / Chapter 2.3.5 --- Expression of P-glycoprotein in H19-silenced cells --- p.31 / Chapter 2.3.6 --- Overexpression of H19 RNA in HepG2 cells --- p.34 / Chapter 2.3.7 --- Induction of H19 RNA and MDR1 in HepG2 cells --- p.34 / Chapter 2.4 --- Discussion / Chapter 2.4.1 --- H19 regulation of MDR1 associated drug resistance --- p.38 / Chapter 2.4.2 --- The puzzle of riboregulation in drug resistance --- p.40 / Chapter CHAPTER THREE: --- The ROLES OF PTB AND IMP1 IN H19-RELATED MDR1 EXPRESSION OF HUMAN HEPATOCELLULAR CARCINOMA HepG2 CELLS / Chapter 3.1 --- Introduction / Chapter 3.1.1 --- H19 RNA binding proteins --- p.43 / Chapter 3.2 --- Materials and methods / Chapter 3.2.1 --- Materials --- p.46 / Chapter 3.2.2 --- Methods / Chapter 3.2.2.1 --- Cell culture --- p.48 / Chapter 3.2.2.2 --- Plasmid construction and stable cell transfection --- p.48 / Chapter 3.2.2.3 --- RNA extraction and RT-PCR --- p.48 / Chapter 3.2.2.4 --- MTT drug sensitivity assay --- p.48 / Chapter 3.2.2.5 --- Western blot analysis --- p.48 / Chapter 3.2.2.6 --- Real-time PCR analysis of gene expression --- p.49 / Chapter 3.2.2.7 --- DOX efflux assay --- p.49 / Chapter 3.3 --- Results / Chapter 3.3.1 --- PTB knockdown increased P-glycoprotein expression --- p.51 / Chapter 3.3.2 --- IMP1 knockdown decreased MDR1 /P-glycoprotein expression --- p.54 / Chapter 3.3.3 --- Altered drug sensitivity in IMP 1 -knockdown cells --- p.60 / Chapter 3.4 --- Discussion / Chapter 3.4.1 --- Antagonistic effect of PTB and IMP1 on H19/MDR1 expressions --- p.64 / Chapter 3.4.2 --- Complexity of riboregulation --- p.65 / Chapter CHAPTER FOUR: --- IDENTIFICATION OF H19 RNA BINDING PROTEINS FROM HUMAN HEPATOCELLULAR CARCINOMA HepG2 CELLS / Chapter 4.1 --- Introduction / Chapter 4.1.1 --- Overview of RNA-protein interactions --- p.69 / Chapter 4.1.2 --- Methodology in the study of RNA-protein interactions --- p.71 / Chapter 4.1.3 --- Identification of RNA-binding proteins --- p.72 / Chapter 4.2 --- Materials and methods / Chapter 4.2.1 --- Materials --- p.75 / Chapter 4.2.2 --- Methods / Chapter 4.2.2.1 --- Screening of H19 cDNA from human placenta cDNA library --- p.78 / Chapter 4.2.2.2 --- Preparation of nuclear and cytoplasmic extracts from HepG2 cells / Chapter 4.2.2.3 --- In vitro RNA transcription and RNA labeling --- p.80 / Chapter 4.2.2.4 --- RNA electrophoretic mobility shift assay --- p.81 / Chapter 4.2.2.5 --- In vitro UV-crosslinking assay --- p.82 / Chapter 4.2.2.6 --- Preparation of RNA-affinity column and isolation of RNA binding proteins --- p.83 / Chapter 4.2.2.7 --- In-gel digestion and MALDI-TOF mass spectrometry --- p.84 / Chapter 4.3 --- Results / Chapter 4.3.1 --- Screening of H19 cDNA and preparation ofH19 RNA --- p.86 / Chapter 4.3.2 --- Electrophoretic mobility shift analysis of H19 RNA with HepG2 cytoplasmic extract --- p.87 / Chapter 4.3.3 --- UV-crosslinking of H19 RNA with HepG2 nuclear and cytoplasmic extract --- p.90 / Chapter 4.3.4 --- Isolation of H19 RNA binding proteins by RNA-affmity chromatography --- p.94 / Chapter 4.3.5 --- Confirmation of PTB and IMP1 as H19 RNA binding protein --- p.96 / Chapter 4.3.6 --- MALDI-TOF mass spectrometric analysis of isolated H19 RNA binding proteins --- p.96 / Chapter 4.4 --- Discussion / Chapter 4.4.1 --- RNA-protein interactions: an initial step for mechanistic study --- p.99 / Chapter 4.4.2 --- In vitro and in vivo methods for isolation of RNA binding proteins --- p.101 / Chapter 4.4.3 --- Novel role of hnRNP M protein in H19 RNA binding --- p.103 / Chapter CHAPTER FIVE: --- THE ROLE OF PTB IN APOPTOSIS / Chapter 5.1 --- Introduction / Chapter 5.1.1 --- Overview of polypyrimidine tract-binding protein in RNA processing and post-transcriptional gene regulation --- p.106 / Chapter 5.1.2 --- Evidences of polyrimidine-tract binding protein in the regulation of apoptosis --- p.108 / Chapter 5.2 --- Materials and methods / Chapter 5.2.1 --- Materials --- p.111 / Chapter 5.2.2 --- Methods / Chapter 5.2.2.1 --- Cell culture --- p.114 / Chapter 5.2.2.2 --- Stable cell transfection in A431 cells --- p.114 / Chapter 5.2.2.3 --- Western Blot analysis --- p.114 / Chapter 5.2.2.4 --- MTT drug sensitivity assay --- p.114 / Chapter 5.2.2.5 --- DNA fragmentation assay --- p.115 / Chapter 5.2.2.6 --- Flow cytometry analysis of apoptosis --- p.115 / Chapter 5.2.2.7 --- Caspase activity assay --- p.116 / Chapter 5.3 --- Results / Chapter 5.3.1 --- Taxol as an apoptosis inducer in HepG2 cells --- p.117 / Chapter 5.3.2 --- PTB was cleaved during Taxol-induced apoptosis --- p.118 / Chapter 5.3.3 --- PTB knockdown increased Taxol cytotoxicity and apoptosis --- p.118 / Chapter 5.3.4 --- Effect of PTB knockdown on drug sensitivity of cells --- p.121 / Chapter 5.3.5 --- Effect of PTB knockdown on other drug-induced apoptosis --- p.121 / Chapter 5.3.6 --- Effect of PTB knockdown on the basal expressions of genes in apoptosis pathway --- p.126 / Chapter 5.3.7 --- The role of caspase-9 activation in PTB-regulated apoptosis --- p.129 / Chapter 5.3.8 --- The effect of PTB knockdown on pro-caspase-9 expression and Taxol-induced apoptosis in A431 cells --- p.133 / Chapter 5.3.9 --- The role of PTB in the regulation of intrinsic apoptosis pathway --- p.136 / Chapter 5.4 --- Discussion / Chapter 5.4.1 --- The role of PTB in intrinsic apoptosis pathway --- p.138 / Chapter 5.4.2 --- PTB in regulation of pro-caspase-9 expression --- p.139 / Chapter CHAPTER SIX: --- GENERAL DISCUSSION AND CONCLUSION / Chapter 6.1 --- H19 as a potential target in anti-cancer gene therapy --- p.143 / Chapter 6.2 --- Conclusion --- p.144 / Chapter 6.3 --- Unanswered questions and future work --- p.145 / Chapter 6.4 --- A proposed model for H19 pathway --- p.148 / REFERENCES --- p.151

研究背景和目的 / 高血壓和糖尿病是人群中常見的疾病，兩者常共同存在，其共存的病理生理機制非常複雜，其中腎素血管景張素系統功能紊亂起重要作用。多個研究表明血管緊張素轉化晦抑制劑和血管緊張素II 1 型受體阻滯劑通過調節不同基因的表達，發揮其保護心血管和腎臟功能的效用。然而，目前仍缺乏遠兩類藥物影響全基因表達譜的全面調查。因此，本研究應用全基因表達譜晶片技術，檢測分析了高血壓和糖尿病並發的病人在服用安慰劑、雷米普利(ramipril)和替米沙坦(telmisartan)後的全基因表達譜的變化，從而全面評估了血管緊張素轉化臨抑制劑和血管繁張素II 1 型受體阻滯劑對相關基因的轉錄調控作用。 / 方法 / 11 名患有高血壓和糖尿病的病人(男性5 名)在服用安慰劑最少2 星期后，以隨機吹序接受為期各6 星期的雷米普利和替米沙坦治療，並分別在安慰劑期和2 個藥物治療期結束后提取心A 進行全基因表達譜分析。 / 結果 / 與服用安慰劑時的全基因表達譜相比，雷米普利治療后有267 個基因的表達降低， 99 個基因的表達增強。表達差異幅度為-2.0 至1.3 (P < 0.05) 。表達下降的基因主要與血管平滑肌收縮、炎症反應和氧化壓力相關。表達增強的基因主要與心血管炎症反應負調節相關。基因共表達網絡分析表明， 2 個共表達基因組與雷米普利的降血壓作用相闕， 3 個共表達基因組與肥胖相關。 / 與服用安慰劑時的全基因表達譜相比， 替米拉)、坦治療后有55 個基因表達降低， 158 個基因的表達增強。表達差異幅度為-1. 9 至1.3 (P < 0.05) 。表達增強的基因主要與脂質代謝、糖代謝和抗炎症因子作用相關。基因共表達網絡分析表明， 2 個共表達基因組與替米沙坦對24 小時舒張壓負荷量的作用相關， 2 個共表達基因組則與總膽固醇， 低密度脂蛋白膽固醇和C 反應蛋白相關。 / 結論 / 本論文描述了高血壓和2 型糖尿病病患全基因組表達的總體模式及經藥物治療後表達譜的相應改變， 為今後進一步研究腎素血管緊張素系統抑制劑和高血壓、糖尿病發展進程的相互作用提供了方向。 / Background and aim: Pathophysiological mechanisms underpinning the coexistence of hypertension and type 2 diabetes are complex systemic responses involving dysregulation of the renin-angiotensin system (RAS). We conducted this study to investigate the genome wide gene expression changes in patients with both hypertension and diabetes at three treatment stages, including placebo, ramipril and telmisartan. This study aimed to obtain a panoramic view of interactions between gene transcription and antihypertensive therapy by RAS inhibition. / Methods: 11 diabetic patients (S men) with hypertension were treated with placebo for at least 2 weeks followed by 6 weeks randomised crossover treatment with ramipril Smg daily and telmisartan 40mg daily, respectively. Total RNA were extracted from leukocytes at the end of placebo and each treatment period, and were hybridized to the whole transcript microarray. The limma package for R was used to identify differentially expressed genes between placebo and the 2 active treatments. The weighted gene coexpression network analysis (WGCNA) was applied to identify groups of genes (modules) highly correlated to a common biological function in pathogenesis and progression of hypertension and diabetes. / Results: There were 267 genes down-regulated and 99 genes up-regulated with ramipril. Fold changes of gene expression were ranged from -2.0 to 1.3 (P < 0.05). The down-regulated genes were involved in vascular signalling pathways responsible for vascular smooth muscle contraction, inflammation and oxidative stress. The up-regulated genes were associated with negative regulation of cardiovascular inflammation. The WGCNA identified 17 coexpression gene modules related to ramipril. The midnight blue (57 genes, r < -0.44, P < 0.05) and magenta (190 genes, r < -0.44, P < 0.05) modules were significantly correlated to blood pressure differences between placebo and ramipril. / There were 55 genes down-regulated and 158 genes up-regulated with telmisartan. Fold changes of gene expression were ranged from -1.9 to 1.3 (P < 0.05). The down-regulated genes were mainly associated with cardiovascular inflammation and oxidative stress. The up-regulated genes were associated with lipid and glucose metabolism and anti-inflammatory actions. The WGCNA identified 8 coexpression gene modules related to telmisartan. The black (56 genes, r = 0.46, P = 0.03) and turquoise (1340 genes, r = -0.48, P = 0.02) modules were correlated with diastolic blood pressure load. The blue (1027 genes) module was enriched with genes correlated with total cholesterol (r = - 0.52, P = 0.01), LDL-C (r = - 0.58, P = 0.004), and hsCRP (r = -0.57, P = 0.006). The green module (272 genes) was significantly correlated with LDL-C (r = - 0.44, P = 0.04) and hsCRP (r = - 0.59, P = 0.004). / Conclusion: Genome wide gene expression profiling in this study describes the general pattern and treatment responses in patients with hypertension and type 2 diabetes, which suggests future directions for further investigations on the interaction between actions of the RAS blockers and disease progression. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Deng, Hanbing. / "December 2011." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 198-256). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Declaration --- p.i / Publications --- p.ii / Abstract --- p.iv / 論文摘要 --- p.vi / Acknowledgements --- p.viii / Table of Contents --- p.x / List of tables --- p.xiv / List of figures --- p.xv / List of appendices --- p.xvii / List of abbreviations --- p.xviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Overview --- p.1 / Chapter 1.2 --- Epidemiology --- p.6 / Chapter 1.2.1 --- Epidemiology of hypertension --- p.9 / Chapter 1.2.2 --- Epidemiology of type 2 diabetes --- p.10 / Chapter 1.3 --- Aetiology --- p.13 / Chapter 1.3.1 --- Ageing --- p.13 / Chapter 1.3.1.1 --- Age-induced artery stiffness --- p.14 / Chapter 1.3.1.2 --- Age-related endothelial dysfunction --- p.14 / Chapter 1.3.2 --- The renin-angiotensin system (RAS) --- p.16 / Chapter 1.3.2.1 --- The local RAS --- p.20 / Chapter 1.3.2.2 --- The RAS and insulin resistance --- p.22 / Chapter 1.3.2.3 --- The RAS and inflammation --- p.26 / Chapter 1.3.2.4 --- The RAS and oxidative stress --- p.28 / Chapter 1.3.3 --- Obesity --- p.31 / Chapter 1.3.3.1 --- Obesity and renin-angiotensin system (RAS) --- p.33 / Chapter 1.3.3.2 --- Obesity and insulin resistance --- p.36 / Chapter 1.3.3.3 --- Obesity and oxidative stress --- p.38 / Chapter 1.3.3.4 --- Obesity and sympathetic nervous system (SNS) --- p.38 / Chapter 1.4 --- Pharmacogenomics of antihypertensive therapy --- p.39 / Chapter 1.4.1 --- Angiotensin-converting enzyme inhibitors (ACEIs) --- p.41 / Chapter 1.4.2 --- Angiotensin II type 1 receptor blockers (ARBs) --- p.43 / Chapter Chapter 2 --- Aim --- p.59 / Chapter Chapter 3 --- Methods --- p.60 / Chapter 3.1 --- Subjects --- p.60 / Chapter 3.1.1 --- Subject recruitment protocol --- p.60 / Chapter 3.1.2 --- Definition of type 2 diabetes --- p.62 / Chapter 3.1.3 --- Definition of obesity --- p.62 / Chapter 3.1.4 --- Definition of dyslipidaemia --- p.63 / Chapter 3.2 --- Study design and procedure --- p.64 / Chapter 3.2.1 --- Blood pressure assessments --- p.65 / Chapter 3.2.2 --- Anthropometric measurements --- p.68 / Chapter 3.2.3 --- Medical history, life style and side effect evaluation --- p.68 / Chapter 3.2.4 --- RNA isolation --- p.68 / Chapter 3.2.5 --- RNA quality assessment --- p.70 / Chapter 3.2.6 --- Oligonucleotide microarrays --- p.71 / Chapter 3.2.7 --- DNA extraction --- p.75 / Chapter 3.2.8 --- Biomedical measurements --- p.76 / Chapter 3.2.8.1 --- Glycosylated haemoglobin Alc (HbA₁c) --- p.77 / Chapter 3.2.8.2 --- Fasting plasma glucose (FP G) --- p.77 / Chapter 3.2.8.3 --- Fasting insulin --- p.77 / Chapter 3.2.8.4 --- Plasma urate --- p.77 / Chapter 3.2.8.5 --- High sensitive C-reactive protein (hsCRP) --- p.78 / Chapter 3.2.8.6 --- Fasting plasma triglycerides (TG) --- p.78 / Chapter 3.2.8.7 --- Fasting plasma cholesterols --- p.78 / Chapter 3.2.8.8 --- Renal and liver functions --- p.78 / Chapter 3.2.8.9 --- Urinary parameters --- p.79 / Chapter 3.3 --- Statistical Analysis --- p.79 / Chapter 3.3.1 --- Statistical analysis of clinical and biomedical data --- p.79 / Chapter 3.3.2 --- Analysis of microarray data --- p.80 / Chapter 3.3.2.1 --- Raw data assessment --- p.80 / Chapter 3.3.2.2 --- Data normalisation --- p.92 / Chapter 3.3.2.3 --- Data filtering --- p.96 / Chapter 3.3.2.4 --- Linear models for assessment of differential expression --- p.96 / Chapter 3.3.2.5 --- Weighted gene coexpression network analysis --- p.101 / Chapter 3.3.2.6 --- Network visualisation and gene ontology analysis --- p.102 / Chapter 3.3.3 --- Sample size calculation --- p.103 / Chapter Chapter 4 --- Results --- p.104 / Chapter 4.1 --- Demographic and biomedical characteristics at baseline --- p.104 / Chapter 4.1.1 --- Hypertension and diabetes status at baseline --- p.108 / Chapter 4.1.2 --- Prevalence of dyslipidaemia --- p.108 / Chapter 4.1.3 --- Prevalence of obesity --- p.109 / Chapter 4.1.4 --- Prevalence of metabolic syndrome --- p.109 / Chapter 4.1.5 --- Inflammation markers --- p.110 / Chapter 4.2 --- Blood pressure response to the RAS blockers --- p.110 / Chapter 4.2.1 --- Clinic blood pressure --- p.110 / Chapter 4.2.2 --- 24-hour ambulatory blood pressure --- p.112 / Chapter 4.3 --- Biomedical characteristics --- p.118 / Chapter 4.4 --- Compliance, side effects and adverse events --- p.120 / Chapter 4.5 --- Gene expression differences between treatments --- p.121 / Chapter 4.5.1 --- Gene expression differences between placebo and ramipril --- p.121 / Chapter 4.5.1.1 --- Expression changes in genes related to regulation of transcription with ramipril --- p.122 / Chapter 4.5.1.2 --- Expression changes with ramipril in genes related to molecular mechanism of cardiovascular changes in hypertension --- p.125 / Chapter 4.5.1.3 --- Expression changes in genes related to blood pressure with ramipril --- p.128 / Chapter 4.5.1.4 --- Expression changes in genes related to fatty acid metabolism with ramipril --- p.130 / Chapter 4.5.1.5 --- Expression changes in genes related to inflammation with ramipril --- p.130 / Chapter 4.5.1.6 --- Expression changes in genes related to oxidative stress with ramipril --- p.133 / Chapter 4.5.1.7 --- Power estimation --- p.133 / Chapter 4.5.2 --- Gene expression differences between placebo and telmisartan --- p.135 / Chapter 4.5.2.1 --- Changes in regulation oftranscription with telmisartan --- p.137 / Chapter 4.5.2.2 --- Expression changes in genes related to glucose metabolism with telmisartan --- p.141 / Chapter 4.5.2.3 --- Expression changes in genes related to lipid metabolism with telmisartan --- p.143 / Chapter 4.5.2.4 --- Expression changes in genes related to inflammation with telmisartan --- p.143 / Chapter 4.5.2.5 --- Power estimation --- p.145 / Chapter 4.5.3 --- WGCNA for comparison between placebo and ramipriI --- p.147 / Chapter 4.5.3.1 --- Midnight blue module and clinical responses to ramipril --- p.152 / Chapter 4.5.3.2 --- Magenta module and blood pressure responses to ramipril --- p.154 / Chapter 4.5.3.3 --- Yellow module and clinical responses to ramipril --- p.158 / Chapter 4.5.3.4 --- Red module and clinical responses to ramipril --- p.161 / Chapter 4.5.3.5 --- Salmon module and clinical responses to ramipril --- p.163 / Chapter 4.5.4 --- WGCNA for comparison between placebo and telmisaItan --- p.168 / Chapter 4.5.4.1 --- Diastolic blood pressure load and gene coexpression modules --- p.168 / Chapter 4.5.4.2 --- Lipids, hsCRP and gene coexpression modules --- p.172 / Chapter Chapter 5 --- Discussion --- p.176 / Chapter 5.1 --- Gene expression changes related to ramipril --- p.177 / Chapter 5.1.1 --- Gene expression changes and blood pressure reduction by ramipri1 --- p.177 / Chapter 5.1.2 --- Gene expression changes and vascular protection by ramipri1 --- p.181 / Chapter 5.1.3 --- Obesity and gene expression changes by ramipril --- p.183 / Chapter 5.2 --- Gene expression changes related to telmisartan --- p.185 / Chapter 5.2.1 --- Blood pressure and coexpressed gene modules with telmisartan --- p.185 / Chapter 5.2.2 --- Lipid metabolism and gene expression changes by telmisartan --- p.187 / Chapter 5.2.3 --- Glucose metabolism and gene expression changes by telmisartan --- p.189 / Chapter 5.2.4 --- hsCRP and gene expression changes by telmisartan --- p.190 / Chapter 5.3 --- Limitations of this study and future directions of research --- p.191 / Chapter Chapter 6 --- Conclusion --- p.194 / References --- p.198 / Appendices --- p.257