Predisposition to autoimmune diseases such as, rheumatoid arthritis, diabetes, and multiple sclerosis, is caused by the effect of multiple genes and a strong influence from the environment. In this study, I have investigated genetic factors that confer susceptibility to rheumatoid arthritis in a rat model. This work has led to the identification of several chromosomal regions, containing uncharacterized genes that directly or indirectly are associated to the arthritis development in these rats. We have observed that timing, gender, and genetic interactions are features that play a part in the effect that these genetic factors exert. Unarguably, animal models for human disorders display differences to the human form of disease. An important fact is however that the same chromosomal regions are identified in both rodent and human studies, which suggests that there are genetic factors that we have in common, which are involved directly or indirectly with an autoimmune response. Focusing the interest on these similarities, and on the possibility to apply a wide set of genetic tools, make animal models an invaluable, and probably necessary, instrument to dissect the genetic component of complex disorders. To fully comprehend the genetic basis for a complex disorder like this, will require understanding of how multiple genes interact with each other to cause disease. We have been able to demonstrate that chronic arthritis, in a rat model for rheumatoid arthritis, is regulated by several genes and that these act during different temporal phases of the disease. These findings will hopefully contribute to our understanding of the etiology and progression of rheumatoid arthritis.

This thesis presents results from genetic studies conducted in the chicken (Gallus gallus). The domestication of chicken is believed to have been initiated approximately 7,000 – 9,000 years ago in Southeast Asia. Since that time, selective breeding has altered the appearance of the wild ancestor, creating highly specialized chicken lines developed for egg and meat production. The first part of this thesis describes a detailed genetic analysis conducted on an F2 intercross between two phenotypically diverse chicken lines. The two parental lines used in this experiment originated from the same base population and have been developed by divergent selection for juvenile body-weight. Selection during forty generations has resulted in an eight-fold difference in body-weight between the High-Weight Selected (HWS) and Low-Weight Selected (LWS) line. In an attempt to identify the genetic factors differentiating the two lines, a large intercross population was bred to map Quantitative Trait Loci (QTL) affecting body-weight traits. A linkage map was constructed which included 434 genetic markers covering 31 of the 38 chicken autosomes. Although there is a dramatic phenotypic difference between the two founder lines, the QTL analysis for marginal effect could only identify seven QTL, each with small additive effects, influencing body-weight. We extended the genetic analysis to also include a model testing for pair-wise interactions between loci (epistasis). The analysis revealed 15 QTL pairs that affect body-weight and several of those formed a network of interacting loci. These results suggest that the genetic basis for the large difference in body-weight is most likely a result of a combined effect of multiple genetic factors, including QTL with small additive effects in combination with pair-wise interactions between QTL. The second part of this thesis presents two linkage maps. The first map constructed was of the chicken Z chromosome, the second used a genome-wide marker set, including 12,945 SNP markers, to build an updated consensus map of the chicken genome. The resulting consensus map includes 9,268 genetic markers and covers 33 chromosomes, still leaving five microchromosomes without marker coverage. The genome average rate of recombination was estimated to 3.1 cM/Mb, but varied considerably between and within chromosomes. A general trend of elevated recombination rates towards telomeric ends and lower rates near centromeres was observed. This was in concordance to previous reports from mammalian species. Recombination rates in chicken were also found to be highly positively correlated with GC-rich sequences.

Fusarium verticillioides è responsabile della fusariosi della spiga in mais e della contaminazione della granella con micotossine. Sono state individuate le regioni geniche e i geni candidati per la resistenza a Fusarium dal confronto tra una linea di mais resistente (CO441) e una suscettibile (CO354), impiegando tre diversi approcci: analisi QTL, analisi trascrittomica (RNASeq) e analisi metabolomica. 184 famiglie F2:3 (CO441xCO354) sono state valutate in due diversi ambienti nell’anno 2011 e inoculate artificialmente con due diverse tecniche (forchetta e stuzzicadente). E’ stata rilevata una significativa variazione genotipica in risposta all’infezione. Sulla base di una mappa preliminare di linkage molecolare contenente 74 marcatori microsatelliti polimorfici, sono stati determinati 8 QTLs comuni alla resistenza alla fusariosi della spiga e alla riduzione della contaminazione da fumonisine. Sono stati considerati geni candidati per la resistenza i geni differenzialmente espressi, risultanti dall’ RNASeq, in semi di mais CO441 prima e 72 ore dopo l’infezione. I metaboliti putativi correlati alla resistenza sono stati rilevati tramite high resolution LC-MS in entrambe le linee di mais. I geni candidati e i metaboliti mappano in pathway coinvolti nei meccanismi di difesa: fenilalanina, tirosina e triptofano biosintesi, fenilpropanoidi e flavonoidi biosintesi, metabolismo dell’acido linoleico e α-linolenico. Abbondanti trascritti derivano dalla biosintesi dei terpenoidi e dei diterpenoidi. Nei geni candidati verranno ricercati polimorfismi fra le due linee di mais e che andranno ad arricchire la mappa di linkage molecolare. / Fusarium verticillioides is responsible for Fusarium ear rot in maize and mycotoxin contamination of grain. Genomic regions and candidate genes for resistance to Fusarium were detected through the comparison of resistant (CO441) and susceptible (CO354) maize lines, by following three different approaches: Quantitative Trait Locus (QTL), transcriptomic (RNASeq) and metabolomic analyses. 184 F2:3 families (CO441xCO354) were evaluated in two different environments in 2011 and artificially infected with two side-needle inoculation methods (pin-bar and toothpick). Significant genotypic variation in response to infection was detected. On the basis of a genetic draft map containing 74 polymorphic SSRs markers, 8 common QTLs for Fusarium ear rot resistance and fumonisin contamination reduction were revealed. Candidate genes for resistance resulted from differentially expressed genes before and 72 hours post infection of CO441 kernels through RNASeq technology. Putative metabolites related to resistance were detected through high resolution LC-MS in both maize lines. Candidate genes and metabolites mapped in pathways involved in defense mechanism: phenylalanine, tyrosine and tryptophan biosynthesis, phenylpropanoid and flavonoid biosynthesis, linoleic and α-linolenic acid metabolism. Abundant genic transcripts derived from terpenoid and diterpenoid biosynthesis. Candidate genes will be screened for polymorphisms between the two maize lines in order to enrich the linkage map.

En els darrers anys, la important reconversió varietal ha permès una millor qualitat, més adaptada tan a les exigències de la producció com de la distribució i del consumidor. La primera generació de milloradors van posar tot el seu èmfasi en millorar les característiques comercials de la fruita com el color, la fermesa i el sabor. Tanmateix el mercat actual exigeix altres atributs de tipus organolèptic i nutricional, addicionals als anteriors. Entendre la base genètica que controla cadascun dels caràcters determinarà la nostra capacitat per obtenir uns fruits més atractius i sans per al consumidor.A la població 'Texas' × 'Earlygold' (T×E) s'han mapat 206 gens candidats (GCs) relacionats amb l'expressió dels caràcters de qualitat de la fruita (creixement i maduració del fruit, textura, color, contingut de sucres i àcids orgànics i aroma) i 18 gens al·lergògens de presseguer i/o ametller responsables de l'aparició de reaccions al·lèrgiques. La comparació entre la posició dels GCs mapats i la dels QTLs detectats ha permès trobar algunes co-localitzacions.Addicionalment, l'anàlisi comparativa entre la seqüència dels marcadors mapats a Prunus amb el mapa de la maduixa diploide i la seqüència completa de la pomera mostra elements comuns. La presència de blocs sintènics facilitarà la transferència del coneixement genètic entre les tres espècies i, a la vegada, permetrà proposar un hipotètic genoma ancestral per la família Rosaceae. / Fruit quality is a very important trait in breeding programs of rosaceous crops. In addition to attributes such as appearance, flavour, scent and texture, breeders focus more and more on crucial aspects like nutritional quality and the absence or significant reductions of allergenic compounds for fruit health and safety. Understanding the genetic basis that controls each character determines our ability to obtain more attractive and healthy fruit to consumers.In the present study 206 candidate genes (CGs) associated with the expression of the characteristics of fruit quality (growth and fruit ripening, texture, colour, sugar content and organic acids and aroma) and 18 genes peach and / or almond allergens responsible for allergic reactions have been mapped in the Prunus reference map. The comparison between the position of the CGs and the QTLs previously detected allow us to find some co-localizations.Additionally, the comparative analysis between the sequences of molecular markers that are anchored into the Prunus and Fragaria reference maps and the Malus genome sequence shows common features. The presence of syntenic blocks facilitates the transference of genetic information between the three species and, in turn, would propose a hypothetical ancestral genome for Rosaceae family. / RESUMENEn los últimos años, la importante reconversión varietal ha permitido una mejor calidad, más adaptada tanto a las exigencias de la producción como de la distribución y del consumidor. La primera generación de mejoradores puso todo su énfasis en mejorar las características comerciales de la fruta como el color, la firmeza y el sabor. Sin embargo el mercado actual exige otros atributos de tipo organoléptico y nutricional, adicionales a los anteriores. Entender la base genética que controla cada uno de los caracteres determinará nuestra capacidad para obtener unos frutos más atractivos y sanos para el consumidor.En la población 'Texas' × 'Earlygold' (T×E) se han mapeado 206 genes candidatos (GCs) relacionados con la expresión de los caracteres de calidad de la fruta (crecimiento y maduración del fruto, textura, color, contenido de azúcares y ácidos orgánicos y aroma) y 18 genes alérgenos de melocotonero y/o almendro responsables de la aparición de reacciones alérgicas. La comparación entre la posición de los GCs mapeados y la de los QTLs detectados ha permitido encontrar algunas co-localizaciones.Adicionalmente, el análisis comparativo entre la secuencia de los marcadores mapeados a Prunus con el mapa de la fresa diploide y la secuencia completa del manzano muestra elementos comunes. La presencia de bloques sinténicos facilitará la transferencia del conocimiento genético entre las tres especies y, a la vez, permitirá proponer un hipotético genoma ancestral para la familia Rosaceae.

L'étude de l'hérédité de caractères quantitatifs est au coeur de la génétique depuis l'avènement de cette science au siècle dernier. La génétique quantitative dispose désormais d'un cadre expérimental et théorique bien établi pour étudier les facteurs génétiques sous-jacents à l'hérédité de caractères complexes, que ce soit dans un but cognitif ou pour épauler les programmes d'amélioration variétale chez les espèces d'intérêt agronomique. Généralement, l'étude du déterminisme génétique de caractères quantitatifs s'articule autour de trois étapes majeures: i) déterminer les principaux locus impliqués dans la variation observée (dénommés QTL pour (( Quantitative Trait Loci ))), ii) identifier les gènes en cause, iii) discriminer les principales formes alléliques de ces gènes et évaluer leurs effets. L'avènement des marqueurs moléculaires et de la génomique au cours des vingt dernières années a facilité la mise en oeuvre de dispositifs expérimentaux de cartographie de QTL en génétique végétale. Il est désormais possible d'avoir accès, via les bases de données publiques, à une masse importante de résultats de détection de QTL. Parallèlement, pour certaines espèces végétales, l'annotation de leurs génomes fournit une information de plus en plus riche et précise sur la structure et la fonction des gènes. L'objectif de cette thèse était double. D'une part nous avons cherché à développer une nouvelle approche de type méta-analyse pour optimiser le croisement entre les données de QTL et celles issues de la génomique, dans le but de faciliter la recherche de gènes candidats. Une fois ces derniers identifiés, l'association entre leur diversité allélique et la variation du caractère peut

No description available.

The aim of this study was to gain insight into the nature of resistance genes and mechanisms of resistance present in different ascochyta blight (AB) resistant genotypes of lentil to efficiently select non-allelic AB resistance genes mediating different mechanisms of resistance for gene pyramiding. Recombinant inbred lines (RILs) from all possible crosses among AB resistant Lens culinaris genotypes CDC Robin, 964a-46, ILL 7537 and ILL 1704 were subjected to allelism tests. Efforts were also made to understand the genetics of resistance in the L. ervoides accession L-01-827A. LR-18, a RIL population from the cross CDC Robin × 964a-46 was subjected to quantitative trait loci (QTL) mapping using a comprehensive genetic linkage map previously developed from polymorphic SNPs, SSRs and phenotypic markers. Results of allelism tests suggested that genes conditioning resistance to ascochyta blight in all lentil genotypes were non-allelic. Two complementary recessive resistance genes in L-01-827A were detected. QTL analysis indicated that CDC Robin and 964a-46 were different at two AB resistance QTLs. Histological tests suggested that cell death inhibition in CDC Robin, and reduced colonization of epidermal cells in 964a-46 might be the mechanisms of resistance in these genotypes. Comparing the expression of key genes in the salicylic acid (SA) and jasmonic acid (JA) signaling pathways of CDC Robin and 964a-46 suggested that the SA pathway was strongly triggered in 964a-46. However, the JA pathway was triggered in both, but at a lower expression level in 964a-46 than in CDC Robin. RNA-seq analysis revealed a number of candidate defense genes differentially expressed among genotypes with hypothetical actions in different layers of the plant defense machinery. The expression levels of the six candidate defense genes measured by quantitative real-time PCR analysis was correlated with those of RNA-seq. In conclusion, 964a-46 and CDC Robin mediated resistance to ascochyta blight through different resistant mechanisms, making them ideal candidates for resistance gene pyramiding. Gene pyramiding can be accelerated using closely linked markers to CDC Robin and 964a-46 resistance genes identified through QTL analysis.

Le processus de sélection intersexuelle peut impliquer plusieurs mécanismes différents dans le choix du partenaire. Chez la pyrale Achroia grisella, les femelles choisissent les mâles en se basant sur des caractères de leur chant d'avertissement ultrasonique, et de précédentes études ont montré que ce choix peut procurer, à une femelle discriminante, certains bénéfices génétiques indirects. Dans cette thèse, j'ai continué à explorer le mécanisme de bénéfices indirects chez cette espèce en 1) déterminant avec plus de précision un paramètre acoustique, l‟amplitude du chant, qui influence le choix des femelles et en 2) examinant la covariance génétique entre les traits du chant mâle et ceux de la préférence femelle. J'ai constaté qu'en plus de préférer des chants mâles émis avec une plus grande amplitude et une plus grande puissance acoustique, les femelles font également une discrimination en faveur des chants comprenant des forts « pics d'amplitude ». Cependant, mes analyses génétiques moléculaires de la relation entre les traits du signal mâle et ceux de la préférence femelle, n'ont révélé aucune covariance significative, comme prédit par la théorie de la sélection sexuelle. Ces derniers résultats fournissent un aperçu important concernant l‟existence d‟un tempo réduit de la sélection sexuelle, dans les populations naturelles. / The process of inter-sexual selection may involve several different mechanisms of mate choice. In the pyralid moth Achroia grisella, females choose males based on characters of their ultrasonic advertisement song, and previous work has indicated that such choice may afford a discriminating female certain indirect genetic benefits. In this thesis I continued to probe the indirect benefits mechanism in this species by 1) determining with more precision one acoustic character, song amplitude, that influences female choice and by 2) examining the genetic covariance between the male song trait and the female preference trait. I found that in addition to preferring male songs delivered at greater amplitude and with greater acoustic power, females also discriminate in favor of songs including higher 'amplitude peaks'. However, my molecular genetic analyses of the relationships between the male signal and female preference traits did not reveal any significant covariance, as predicted by sexual selection theory. These latter findings provide important insight on the reduced tempo of sexual selection that may exist in natural populations.

No description available.

Dentre o setor agropecuário, a avicultura é a que mais tem demonstrado índices de evolução nos últimos anos. Esses avanços são obtidos principalmente por meio da nutrição, manejo dos animais e seleção genética. A biotecnologia tem ganhado papel de destaque com o uso de marcadores moleculares como ferramenta para acrescentar informações genômicas aos processos de melhoramento convencional. Estudos anteriores em uma população F2 originada do cruzamento de frangos de corte e postura permitiram a identificação de um SNP no gene FGFBP1 (Proteína de ligação do fator de crescimento do fibroblasto 1) (g. 2014 G> A) no cromossomo 4 de Gallus gallus (GGA4). Este gene está em uma região de QTLs associado com rendimentos de coxa e sobrecoxa, peso vivo aos 35 e 41 dias de idade. O objetivo deste trabalho foi investigar um QTL previamente descrito para identificação de polimorfismos adicionais e suas associações com características de importância econômica utilizando testes de associação de um ou mais marcadores. Três genes candidatos posicionais foram identificados nesta região de QTL: KLF3(Krüeppel-like factor 3), SLIT2 (Slit homolog 2) e PPARG (Peroxisome proliferator-activated receptor gamma, coactivator 1alpha). O sequenciamento destes genes em onze (n=11) animais F1 permitiu a identificação de um polimorfismo em cada gene: g.6763 C> T (KLF3), g.187737 C> A (SLIT2) e g.76638826 -/TTTCT (PPARGC1A). Essas mutações foram genotipadas em uma população segregante F2 (n=276) e em uma linhagem pura de corte TT (n=840) da Embrapa Suínos e Aves. A frequência dos alelos para o gene KLF3 na população F2 foi de C=50% T=50% e na pura TT de C=98% T=2%, para o gene SLIT2 na população F2 foi de A=25% C=75% e na pura TT de A=30% C=70%, para o gene PPARGC1A na população F2 foi de Del=43% In=57% e na pura TT Del=33% C=67%, representando que estes polimorfismos estão segregando nas duas populações. Associações destes polimorfismos foram observadas (P<0,05) com várias características de desenvolvimento e carcaça na população F2 e na linhagem pura TT, sendo que algumas foram confirmadas nesta população como: pesos de fígado, coxas, ganhos de peso dos 35 aos 41 dias com g.6763 C> T (KLF3) e pesos das asas, cabeça, carcaça, dorso, coxas, peito, fígado e gordura abdominal com g.76638826 -/TTTCT (PPARGC1A) indicando que esta região de QTL é importante para características de produção e desempenho em frangos de corte. / Within the livestock sector, the broiler industry has showed fastest growing rates in past decades. Those advances were achieved mainly because a better understanding of the nutrition requirements, animal management and animal genetics. Biotechnology has gained a prominent role with the use of molecular markers as a tool for adding genomic information to conventional breeding processes. Previous studies using an F2 population developed from a broiler x layer cross led to the identification of a SNP on the Fibroblast growth factor binding protein 1 (FGFBP1) (g. 2014G> A) on Gallus gallus chromosome 4 (GGA4). This gene is part of a QTL associated with thigh & drumstick yields, weight gain at 35 and 41 days. This paper investigates the previously identified QTL for the identification of additional polymorphisms and their associations with important economic traits using a single and multiple markers tests. Three positional candidate genes were identified on the QTL region: KLF3 (Krüeppel-like factor 3), SLIT2 (Slit homolog 2) and PPARG (Peroxisome proliferator-activated receptor gamma, coactivator 1alpha). Sequencing of those genes was conducted in eleven (n=11) F1 animals and one polymorphism was identified in each gene g.6763 C> T (KLF3), g.187737 C> A (SLIT2) and g.76638826 -/TTTCT (PPARGC1A). These mutations were genotyped in an F2 (n=276) and a pure broiler line (n=840) from Embrapa. The frequency of the genes alleles were: KLF3 gene in F2 population C = 50% T = 50% and pure TT population C = 98% T = 2%; SLIT2 gene in F2 population A = 25% C = 75% and pure TT population A = 30% C = 70%; PPARGC1A gene in F2 population Del =43% and In = 57% and pure TT population Del = 33% C = 67% indicating that those polymorphisms are still segregating in both populations. Association was identified (P < 0,05) with several carcass and development traits in the F2 and Pure TT population, some which were confirmed like liver, drumstick weights, weight gain from 35 to 41 days with g.6763 C> T (KLF3) and wings, had, carcass, back, drumstick, breast and liver and abdominal fat weights with g.76638826 -/TTTCT (PPARGC1A) indicating that this QTL region is important for production and performance traits of broiler.