• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 817
  • 313
  • 142
  • 97
  • 91
  • 36
  • 28
  • 20
  • 14
  • 14
  • 7
  • 6
  • 6
  • 5
  • 5
  • Tagged with
  • 1868
  • 218
  • 175
  • 160
  • 160
  • 148
  • 116
  • 115
  • 96
  • 95
  • 94
  • 91
  • 90
  • 87
  • 86
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
121

Modulation of vascular reactivity by selective estrogen receptor modulators and dihydropyridines in porcine coronary arteries.

January 2005 (has links)
Leung Hok Sum. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 128-147). / Abstracts in English and Chinese. / Declaration --- p.i / Acknowledgements --- p.ii / Abbreviation --- p.iii / Abstract in English --- p.iv / Abstract in Chinese --- p.vi / Contents --- p.viii / Chapter Chapter I - --- Introduction / Chapter 1.1. --- Steroid Hormone --- p.1 / Chapter 1.2. --- Estrogen Receptors --- p.2 / Chapter 1.3. --- Selective Estrogen Receptor Modulators --- p.5 / Chapter 1.3.1. --- Tamoxifen --- p.5 / Chapter 1.3.1.1. --- Cardiovascular Effects of Tamoxifen --- p.6 / Chapter 1.3.1.2. --- Acute Vascular Effects of Tamoxifen --- p.6 / Chapter 1.3.1.3. --- Chronic Vascular Effects of Tamoxifen --- p.7 / Chapter 1.3.1.4. --- Antioxidant Effects of Tamoxifen --- p.8 / Chapter 1.3.2. --- Raloxifene --- p.8 / Chapter 1.3.2.1. --- Cardiovascular Effects of Raloxifene --- p.8 / Chapter 1.3.2.2. --- Acute Vascular Effects of Raloxifene --- p.9 / Chapter 1.3.2.3. --- Chronic Vascular Effects of Raloxifene --- p.10 / Chapter 1.3.2.4. --- Ovariectomy and Raloxifene Treatment --- p.11 / Chapter 1.4. --- Mechanism of Action of SERMs --- p.15 / Chapter 1.5. --- Effects of Functional Endothelium and Nitric Oxide --- p.18 / Chapter 1.6. --- Dihydropyridine (DHP) Calcium Channel Antagonists --- p.19 / Chapter 1.6.1. --- Development of Newer Generation of Dihydropyridines --- p.19 / Chapter 1.6.2. --- Effects of Dihydropyridines on Vascular Endothelium (I) --- p.20 / Chapter 1.6.3. --- Effects of Dihydropyridines on Vascular Endothelium (II) --- p.21 / Chapter 1.6.4. --- Effects of Dihydropyridines on Nitric Oxide Synthase (NOS) --- p.21 / Chapter 1.6.5. --- Clinical Studies of Dihydropyridines --- p.22 / Chapter 1.7. --- Vascular Ion Channels --- p.25 / Chapter 1.8. --- Objectives of The Present Study --- p.26 / Chapter Chapter II - --- Materials and Methods / Chapter 2.1. --- Tissue Preparation --- p.27 / Chapter 2.1.1. --- Preparation of The Porcine Left Circumflex Coronary Arteries --- p.27 / Chapter 2.1.2. --- Removal of Functional Endothelium --- p.27 / Chapter 2.1.3. --- Organ Bath Setup --- p.27 / Chapter 2.1.4. --- Isometric Force Measurement --- p.29 / Chapter 2.2. --- In situ Endothelial [Ca2+]i Imaging --- p.29 / Chapter 2.2.1. --- Preparation of Porcine Left Circumflex Coronary Arteries --- p.29 / Chapter 2.2.2. --- Setup For In situ Endothelial [Ca2+]i Imaging --- p.30 / Chapter 2.3. --- Electrophysiological Measurement of BKCa Current --- p.31 / Chapter 2.3.1. --- Enzymatic Dissociation of Coronary Artery Smooth Muscle Cells --- p.31 / Chapter 2.3.2. --- Electrophysiological Measurement --- p.31 / Chapter 2.4. --- DPPH Free Radical Scavenging Assay --- p.31 / Chapter 2.5. --- Solutions and Drugs --- p.32 / Chapter 2.5.1. --- "Drugs, Chemicals and Enzymes" --- p.32 / Chapter 2.5.2. --- Solutions Used in Force Measurement --- p.34 / Chapter 2.6. --- Statistical Analysis --- p.34 / Chapter Chapter III - --- Tamoxifen-Induced Endothelial Nitric Oxide-Dependent Relaxation in Porcine Coronary Arteries via Ouabain- and BaCl2-Sensitive Mechanisms / Chapter 3.1. --- Abstract --- p.35 / Chapter 3.2. --- Introduction --- p.36 / Chapter 3.3. --- Methods and Materials --- p.37 / Chapter 3.3.1. --- Vessel Preparation --- p.37 / Chapter 3.3.2. --- Isometric Force Measurement --- p.38 / Chapter 3.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.39 / Chapter 3.3.4. --- Chemicals --- p.40 / Chapter 3.3.5. --- Data Analysis --- p.40 / Chapter 3.4. --- Results --- p.41 / Chapter 3.4.1. --- Relaxant Responses --- p.41 / Chapter 3.4.2. --- Effects of Inhibitors of NO-Dependent Relaxation --- p.41 / Chapter 3.4.3. --- Effects of Putative K+ Channel Blockers and Ouabain --- p.41 / Chapter 3.4.4. --- "Effects of Ouabain, Removal of Extracellular K+ Ions and BaCI2" --- p.42 / Chapter 3.4.5. --- SNP-Induced Relaxation --- p.42 / Chapter 3.4.6. --- Effects of Actinomycin D and Cycloheximide --- p.42 / Chapter 3.4.7. --- Relaxant Effect of 17β-Estradiol --- p.43 / Chapter 3.4.8. --- Effects on Endothelial [Ca2+]i in Isolated Coronary Arteries With Endothelium --- p.43 / Chapter 3.5. --- Discussion --- p.53 / Chapter Chapter IV - --- Endothelium-Independent Relaxation to Raloxifene in Porcine Coronary Arteries / Chapter 4.1. --- Abstract --- p.57 / Chapter 4.2. --- Introduction --- p.58 / Chapter 4.3. --- Methods and Materials --- p.59 / Chapter 4.3.1. --- Vessel Preparation --- p.59 / Chapter 4.3.2. --- Isometric Force Measurement --- p.60 / Chapter 4.3.3. --- Electrophysiological Measurement of BKCa Current --- p.61 / Chapter 4.3.3.1. --- Enzymatic Dissociation of Coronary Artery Smooth Muscle --- p.61 / Chapter 4.3.3.2. --- Electrophysiological Measurement --- p.62 / Chapter 4.3.4. --- Chemicals --- p.63 / Chapter 4.3.5. --- Data Analysis --- p.63 / Chapter 4.4. --- Results --- p.64 / Chapter 4.4.1. --- Effect of Raloxifene on Agonist-Induced Contractions --- p.64 / Chapter 4.4.2. --- Role of Endothelium --- p.64 / Chapter 4.4.3. --- Effect of ER Antagonist --- p.65 / Chapter 4.4.4. --- Effect of Putative K+ Channel Blockers --- p.65 / Chapter 4.4.5. --- Effect of Elevated Extracellular K+ Concentrations --- p.65 / Chapter 4.4.6. --- Effects of Raloxifene on BKCa Current --- p.65 / Chapter 4.5. --- Discussion --- p.75 / Chapter Chapter V - --- Therapeutic Concentrations of Raloxifene Augment Bradykinin Mediated Nitric Oxide-Dependent Relaxation in Porcine Coronary Arteries / Chapter 5.1. --- Abstract --- p.78 / Chapter 5.2. --- Introduction --- p.79 / Chapter 5.3. --- Methods and Materials --- p.80 / Chapter 5.3.1. --- Vessel Preparation --- p.80 / Chapter 5.3.2. --- Isometric Force Measurement --- p.80 / Chapter 5.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.81 / Chapter 5.3.4. --- Free Radical Scavenging Assay --- p.82 / Chapter 5.3.5. --- Chemicals --- p.83 / Chapter 5.3.6. --- Data Analysis --- p.83 / Chapter 5.4. --- Results --- p.84 / Chapter 5.4.1. --- Relaxation to Bradykinin --- p.84 / Chapter 5.4.2. --- Effect of Raloxifene on Bradykinin-Induced Relaxation --- p.84 / Chapter 5.4.3. --- Effect of Raloxifene on Relaxation Induced by Substance P and --- p.85 / Chapter 5.4.4. --- Effect of Estrogen on Bradykinin-Induced Relaxation --- p.85 / Chapter 5.4.5. --- Effect of Raloxifene on Sodium Nitroprusside-Induced Relaxation --- p.86 / Chapter 5.4.6. --- Free Radical Scavenging Effect --- p.86 / Chapter 5.4.7. --- Raloxifene Augmentation of Bradykinin-Stimulated Endothelial [Ca2+]i --- p.86 / Chapter 5.5. --- Discussion --- p.99 / Chapter Chapter VI - --- "Cilnidipine, a Slow-Acting Ca2+ Channel Blocker, Induces Relaxation in Porcine Coronary Arteries: Role of Endothelial Nitric Oxide and [Ca2+]i" / Chapter 6.1. --- Abstract --- p.102 / Chapter 6.2. --- Introduction --- p.103 / Chapter 6.3. --- Methods and Materials --- p.104 / Chapter 6.3.1. --- Vessel Preparation --- p.104 / Chapter 6.3.2. --- Isometric Force Measurement --- p.105 / Chapter 6.3.3. --- In situ Endothelial [Ca2+]i Imaging --- p.106 / Chapter 6.3.4. --- Free Radical Scavenging Assay --- p.107 / Chapter 6.3.5. --- Chemicals --- p.108 / Chapter 6.3.6 --- Data Analysis --- p.108 / Chapter 6.4. --- Results --- p.108 / Chapter 6.4.1. --- Relaxant Responses --- p.108 / Chapter 6.4.2. --- Role of the Endothelium --- p.109 / Chapter 6.4.3. --- Effect of Inhibitors of NO-Dependent Relaxation --- p.109 / Chapter 6.4.4. --- Effect of Indomethacin and w-conotoxin --- p.110 / Chapter 6.4.5. --- Effect of Cilnidipine on Sodium Nitroprusside-Induced Relaxation --- p.110 / Chapter 6.4.6. --- Effects on Endothelial [Ca2+]i in Isolated Endothelium-Intact Coronary Arteries --- p.110 / Chapter 6.4.7. --- Free Radical Scavenging Effect --- p.110 / Chapter 6.5. --- Discussion --- p.120 / Chapter Chapter VII - --- General Summary --- p.123 / References --- p.128
122

Analýza vlivu tepelných jevů na termofotovoltaický systém / Analysis of the influence of thermal effects on thermophotovoltaic system

Kolář, Jakub January 2014 (has links)
This semestral thesis focuses on the description of specific renewable resources in the form of thermophotovoltaic cells using selective radiators with micro/nano structures. This work deals with an introduction of renewable resources and specifically focuses on thermophotovoltaic. Thesis describes basic principles, but also influences affecting the proper functioning of these systems. It also focuses on selective radiators, which are created by mikro/nano structures, and factors that can affect their implementation or simulation. Part of the work are also examples of calculations of basic parameters of the structures, which will be used in the simulations. Next chapters are dealing with simulations which are analyzing thermal effects on termophotovoltaic system. Except the analysis itself there is also partial optimalization solving some of the negative thermal effects.
123

Conséquences de la chasse sur l'écologie et la gestion du chamois (Rupicapra rupicapra)

Rughetti, Marco January 2011 (has links)
Harvesting is a human-imposed selective pressure. Harvest-induced mortality is not random and mostly targets heritable traits. Human harvest may impose an artificial selection pressure on life history traits, often opposite to natural selection. Therefore in harvested populations life history strategies will evolve under natural and human imposed selective pressures, favoring individuals with the highest fitness. In ungulate populations hunting is the most common cause of adult mortality. By increasing adult mortality, hunting may have both ecological and evolutionary consequences affecting phenotypic traits and life history strategies. Typically, in sexually dimorphic species large horn and weapon size is the major determinant of success in male-male competition. Large males gain high dominance rank and enjoy high reproductive success. By removing males with large horn and body size, hunters may favor small individuals, opposite to sexual selection. In long lived mammals longevity is the main determinant in female reproductive success. Typically females reproduce once a year, therefore in the energy allocation trade-off they invest more in body maintenance and survival rather than reproduction to increase lifetime reproductive success. By increasing adult female mortality hunting may reduce age and size at maturation, selecting for a strategy of early maturation and great current maternal investment. In this thesis I studied chamois ecology and evolution by comparing hunted and unhunted populations. I tested for possible differences in life history traits and examined the ecological and evolutionary consequence of hunting. In the chamois populations under study phenotypic traits and reproductive strategies were not strongly affected by hunting. There was no evidence of a strong evolutionary effect of sport hunting on horn length or body mass of adult males or yearlings. Although hunters seek long horned males, hunter selectivity is unlikely to lead to an artificial selective pressure on horn size. I found few differences in body and horn size between hunted and protected populations, suggesting the absence of strong effects of hunting on male phenotype. Although yearling body mass declined over time in both hunted populations, environmental factors explained much of the trends. The combination of low variability in adult horn length, weak correlation between horn length and body mass for adult males and strong compensatory horn growth apparently reduced the potential for hunters to selectively remove young adult males with vigorous growth. Although early development in body and horn growth affected reproductive potential in young and senescent females chamois, I found no evidence that female early development affected hunter selectivity. Sport harvest did not appear to have strong impacts on the evolution of phenotypic traits and reproductive strategies of female chamois, likely because of a low harvest rate and weak selection for long-horned females as hunters appeared more concerned with avoiding lactating females. The biology of chamois seems to prevent impact of selective hunting, at least in the case of weak hunting pressure.
124

Utilisation du Stroop émotion pour l'étude de l'effet du vieillissement sur l'attention sélective

Tremblay-Lavoie, Stéphanie January 2011 (has links)
Résumé : La psychologie cognitive s'intéresse depuis quelques années à un effet de positivité qui semble apparaître avec l'avancement en âge. Cet effet serait également lié à la diminution, voire la disparition, d'un biais attentionnel négatif, naturellement présent chez les jeunes adultes. Celui-ci consiste en une plus grande perturbation de l'attention sélective en présence de stimuli négatifs. Une tâche cognitive d'attention sélective très utilisée pour étudier ce biais cognitif est le Stroop émotion. Présentant des mots à valence négative, positive et neutre, il permet de vérifier l'effet d'interférence que produisent ces stimuli sur la capacité d'inhibition. Jusqu'à présent, les rares études utilisant le Stroop émotion auprès d'une population âgée sans trouble cognitif ne présentent pas de consensus permettant de statuer clairement sur la modification de ce biais cognitif dans le vieillissement. La présente étude proposait d'utiliser le Stroop émotion pour observer l'effet du vieillissement sur l'attention sélective, en répondant aux principales recommandations méthodologiques tirées des études précédentes. Il était attendu que les âgés ne devaient pas présenter d'effet d'interférence en réponse aux stimuli négatifs, contrairement aux jeunes adultes. Les résultats obtenus ont toutefois révélé la présence d'un biais attentionnel négatif tant chez les âgés que chez les jeunes adultes. L'interprétation de ces performances est discutée en regard des exigences cognitives du Stroop émotion. Il pourrait ainsi être plus facile de mettre en évidence la diminution du biais attentionnel négatif à l'aide d'une présentation différente des stimuli qui permettrait la mise en place de l'effet de positivité chez les âgés.||Abstract : For some years now, cognitive psychology has taken an interest in a positivity effect that appears with increased age. This effect is claimed to be related to the decrease in, or even disappearance of, a negative attentional bias that is naturally present in young adults; this effect consists in a greater disruption of selective attention in the presence of negative stimuli. A cognitive task measuring selective attention that is often used to study this cognitive bias is the emotional Stroop test. This task presents words with negative, positive and neutral valence and tests how these stimuli interfere with inhibition capacity. To date, the few studies that have used the emotional Stroop in an elderly population without cognitive disorders have not produced a consensus that would give us a clear sense of the change in this cognitive bias with aging. This study proposed to use the emotional Stroop to observe the effect of aging on selective attention by following the main methodological recommendations arising from earlier studies. It was expected that elderly people would not present an interference effect in response to negative stimuli, unlike young adults. However, the results revealed a negative attentional bias in both older and younger adults. This finding is interpreted in relation to the cognitive demands of the emotional Stroop. It could therefore be easier to highlight the decrease in negative attentional bias by using a different method of presenting stimuli, which would reveal the positivity effect in elderly people.
125

Examining mechanisms underlying the selective vulnerability of motor units in a mouse model of Spinal Muscular Atrophy

Thomson, Sophie Rose January 2014 (has links)
Spinal Muscular Atrophy (SMA) is a childhood form of motor neuron disease that causes a progressive paralysis that, in its most severe form, results in death before two years of age. There is currently no cure or treatment for SMA. SMA is caused by a reduction in levels of Survival Motor Neuron (SMN) protein, which results in the degeneration of lower motor neurons. This degeneration is first observed at the neuromuscular junction (NMJ), where pre-synaptic nerve terminals belonging to the motor neuron become dysfunctional and degenerate during the early stages of disease. Several previous studies have shown that the some populations of motor neurons appear to have a resistance to SMA pathology, while other neighbouring populations are vulnerable. In this study, we attempted to elucidate the cause of this vulnerability spectrum. Initially, we characterised the relative vulnerability of ten different motor unit pools in an established mouse model of severe SMA and attempted to correlate these vulnerabilities with quantified aspects of motor unit morphology. From this study, no significant correlation could be found with any aspect of motor unit morphology examined, suggesting that morphological parameters of motor neurons do no influence their relative susceptibility. We then attempted to identify changes in basal gene expression between protected and vulnerable pools of motor units using microarray analysis. Motor unit pools were labelled using a retrograde tracer injected into muscles that had previously been identified as having highly vulnerable or resistant motor units. Labelled motor neuron cell bodies were then isolated from the spinal cord using laser capture micro-dissection and RNA was extracted for microarray analysis. From this study, we identified several molecular pathways and individual genes whose expression levels compared the gene expression profiles of vulnerable and resistant motor units. Thus, molecular differences between motor neuron pools likely underlie their relative vulnerability to degeneration in SMA. Lastly, we attempted to identify a novel peptide that could be used to label synapses, including neuromuscular junctions, in vivo. This would allow us to non-invasively visualise degenerating NMJs and other synapses in human patients without the need for a biopsy. Such a tool would be extremely valuable in assessing the effectiveness of drug trials, both in human patients and animal models, and may also contribute to earlier diagnosis of motor neuron disorders. To identify a potentially suitable peptide, we used a phage display library and panned for peptides that specifically bound to the outer surface of synapses using synaptosome preparations. From this panning we successfully enriched two peptides, the sequences of which were used to manufacture fluorescently tagged peptides.
126

NON-FEEDBACK HIGH SPEED ADAPTIVE EQUALIZERS FOR FQPSK AND OTHER SPECTRAL EFFICIENCY SYSTEMS FOR LEO SATELLITE TELEMETRY SYSTEMS

Haghdad, Mehdi, Feher, Kamilo 10 1900 (has links)
International Telemetering Conference Proceedings / October 22-25, 2001 / Riviera Hotel and Convention Center, Las Vegas, Nevada / A non-feedback adaptive equalizer based on Feher Equalizer (FE) is presented and its performance is evaluated. By artificially adding notch/notches to the corrupted spectrum resulted from selectively faded LEO environments, an artificial symmetry is created and as a result the BER/BLER is improved. The location and the depth of artificial additive notches are based on the shape of the spectrum of the corrupted signal. By measuring the power in narrow bands around certain frequencies the existence of notches around those frequencies are predicted. Based on this information notches with proper depths are added to the main spectrum which results in more symmetry in the spectrum. The selection process of artificial notch/notches are based on the shape of the signal spectrum, which means that this equalizer unlike most conventional equalizer does not need any feedback. The nonfeedback nature of this equalizer improves the adaptation time over that of alternative equalizers The results presented in this paper are based on both MatLab simulations and laboratory hardware measurements.
127

ADVANCE PRACTICAL CHANNEL SIMULATORS FOR LEO SATELLITE CHANNELS WITH SELECTIVE FADING AND DOPPLER SHIFTS

Haghdad, Mehdi, Feher, Kamilo 10 1900 (has links)
International Telemetering Conference Proceedings / October 22-25, 2001 / Riviera Hotel and Convention Center, Las Vegas, Nevada / Dynamic hardware and software schemes for trajectory based simulation of LEO satellite channel are presented and evaluated. The simulation models are based on the practical LEO satellite channels and change dynamically with the trajectory using the latitude and longitude of the LEO satellite as input. The hardware simulator is consisted of a trajectory based selective fade generator, a trajectory based Doppler shifter, trajectory based time shadowing simulator and a standard channel for addition of noise, ACI and CCI. A FQPSK modulated signal is passed through a trajectory based dynamic fade generator and the spectrum is distorted. Then the resulting signal is exposed to a trajectory based dynamic Doppler Shifter, simulating the passage of the satellite overhead. Then the proper AWGN, ACI or CCI is added to the signal. At the final stage the signal is passed through a trajectory based time Shadowing simulator. The software simulator is a dynamic real time simulator written in MatLab and its structure is similar to the hardware simulator.
128

QAM Multi-path Characterization Due to Ocean Scattering

Swanson, Richard, Dimsdle, Jeff, Petersen, Tom, Pasquale, Regina, Bracht, Roger 10 1900 (has links)
International Telemetering Conference Proceedings / October 21, 2002 / Town & Country Hotel and Conference Center, San Diego, California / A series of RF channel flight characterization tests were recently run to benchmark multi-path performance of high-speed quadrature amplitude modulation (QAM) over the ocean surface. The modulation format was differential-phase/absolute-amplitude two level polar 16 QAM. The bit rate was 100 Megabits per second with a symbol period of 40nS. An aircraft radiated the test signal at 5 different altitudes. It made two inward flights, on two different days, at each altitude with vertical and horizontal polarization, respectively. Receivers, using circular antenna polarization, were in two different locations. Analysis of the resulting data shows flat fading and frequency selective fading effects.
129

Soft Detection of Trellis Coded CPM in Frequency-SelectiveChannels

Pham, Tri January 2012 (has links)
Non-linear continuous phase modulation has constant envelope and spectral efficiency, which are desirable for public safety communication systems where both bandwidth and power are limited. A practical design of an innovation based receiver for partial response CPM was recently developed for public safety applications. It is in the form of a linear predictive demodulator with a coefficient look up table. The demodulator shows great performance over multipath fading channels without channel equalization and promises a significant contribution to public safety communication. The work in this thesis is focussed on developing and analyzing modern techniques to improve the receiver performance while maintaining a feasible implementation complexity. Suitable soft output algorithms are incorporated into the demodulator allowing a subsequent convolutional decoder to perform soft decoding. By modifying the design criteria of the predictive demodulator and introducing a feedback loop, an iterative detection scheme is formed for the concatenated structure of demodulator, deinterleaver and decoder. Spatial diversity combining techniques are summarized and a very low complexity combining scheme is developed. It selects the best received sample sequence by considering the average energy of each sequence. In addition, the demodulator is extended to have dual coefficient look up tables supporting its detection by having parallel prediction processes and combining their results. This leads to an improvement in overall demodulator performance. A theoretical proof that only half the number of coefficients need to be stored in memory is also given. Matlab simulations on a Rayleigh fast fading multipath channel have shown that the proposed techniques significantly improve the overall detection accuracy. Each of them provides a good gain in signal to noise ratio or delay spread and when combined, a significant performance gain is achieved.
130

Detecting Signatures of Selection within the Dog Genome

Ratnakumar, Abhirami January 2013 (has links)
Deciphering the genetic basis of phenotypic diversity is one of the central aims of biological research. Domestic animals provide a unique opportunity for making substantial progress towards this goal. Intense positive selection has lead to a rich reservoir of phenotypes and underlying genotypes that can be interrogated using genetic tools to gain insight into the genetic basis of phenotypic diversity. The dog is the most phenotypically diverse mammal. It was domesticated from the grey wolf 11-30,000 years ago. After domestication, a period of intense breeding has lead to the massive phenotypic diversity seen amongst dog breeds today. These two phases of strong positive selection at domestication and at breed creation are likely to have left their signature on the genome. In this thesis, we have analysed genome-wide patterns to detect genomic regions involved in selection in both of these phases. We used whole genome sequences from 60 dogs and 12 wolves, to detect dog domestication selective sweeps. We find evidence for genes involved in memory formation, neurotransmission and starch digestion. To decipher the genetic signals underlying breed diversity, we used genome-wide genotype data from >170,000 SNPs in 509 dogs from 46 different breeds. We find evidence for genes under selection in many breeds, and only a few breeds. In addition, we identify novel sweeps underlying morphology and behavior. Recombination can influence the configuration of alleles present on a haplotype, and can thus increase or decrease the efficiency of selection. The PRDM9 protein has been shown to be important for determining recombination hotspot locations in humans and other mammals, but of all the mammals studied so far the dog is the only one to have a non-functional PRDM9. We used the genome-wide genotype data described above to characterise the fine scale recombination map in dogs. We find that recombination hotspots exist in dogs despite the absence of PRDM9. Moreover, we show that these hotspots are enriched for GC rich peaks and that these peaks are getting stronger over time. Our results show that the absence of PRDM9 has lead to the stabilisation of the recombination landscape in dogs.

Page generated in 0.3616 seconds