Doctor of Philosophy / Department of Agronomy / Geoffrey Morris / Climate change has been anticipated to affect agriculture, with most the profound effect in regions where low input agriculture is being practiced. Understanding of how plants evolved in adaptation to diverse climatic conditions in the presence of local stressors (biotic and abiotic) can be beneficial for improved crop adaptation and yield to ensure food security. Great genetic diversity exists for agroclimatic adaptation in sorghum (Sorghum bicolor L. Moench) but much of it has not been characterized. Thus, limiting its utilization in crop improvement. The application of next-generation sequencing has opened the plant genome for analysis to identify patterns of genome-wide nucleotide variations underlying agroclimatic adaptation. To understand the genetic basis of adaptive traits in sorghum, the genetic architecture of sorghum inflorescence traits was characterized in the first study. Phenotypic data were obtained from multi-environment experiments and used to perform joint linkage and genome-wide association mapping. Mapping results identified previously mapped and novel genetic loci underlying inflorescence morphology in sorghum. Inflorescence traits were found to be under the control of a few large and many moderate and minor effect loci. To demonstrate how our understanding of the genetic basis of adaptive traits can facilitate genomic enabled breeding, genomic prediction analysis was performed with results showing high prediction accuracies for inflorescence traits. In the second study, the sorghum-nested association mapping (NAM) population was used to characterize the genetic architecture of leaf erectness, leaf width, and stem diameter. About 2200 recombinant inbred lines were phenotyped in multiple environments. The obtained phenotypic data was used to perform joint linkage mapping using ~93,000 markers. The proportion of phenotypic variation explained by QTL and their allele frequencies were estimated. Common and moderate effects QTL were found to underlie marker-trait associations. Furthermore, identified QTL co-localized with genes involved in both vegetative and inflorescence development. Our results provide insights into the genetic basis of leaf erectness and stem diameter in sorghum. The identified QTL will also facilitate the development of genomic-enable breeding tools for crop improvement and molecular characterization of the underlying genes Finally, in a third study, 607 Nigerian accessions were genotyped and the resulting genomic data [about 190,000 single nucleotide polymorphisms (SNPs)] was used for downstream analysis. Genome-wide scans of selection and genome-wide association studies (GWAS) were performed and alongside estimates of levels of genetic differentiation and genetic diversity. Results showed that phenotypic variation in the diverse germplasm had been shaped by local adaptation across climatic gradient and can provide plant genetic resources for crop improvement.

Orientador: Marcio Ajudarte Lopes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-15T17:55:17Z (GMT). No. of bitstreams: 1 Santos-Silva_AlanRoger_D.pdf: 1071923 bytes, checksum: 996d56a5e4895653ebcd0b9e1636e7e2 (MD5) Previous issue date: 2010 / Resumo: Predominantemente, o carcinoma espinocelular (CEC) de boca afeta pacientes idosos e com frequência se desenvolve em associação com o consumo de fumo e álcool. Todavia, evidências científicas têm sugerido o aumento da incidência desta malignidade em pacientes com menos de 40 anos de idade e não expostos aos tradicionais fatores de risco. Informações disponíveis referentes ao câncer de boca em pacientes jovens são escassas e controversas, dificultando a compreensão da patogênese, do comportamento biológico e do prognóstico destes tumores. Como consequência, seu tratamento tem sido baseado principalmente na experiência profissional de cada centro médico. Este trabalho teve como objetivos estudar as características demográficas, os fatores de risco e os aspectos clínicos no momento do diagnóstico, além do perfil biológico de CECs de língua em pacientes com até 40 anos. Foi realizada uma análise retrospectiva multiinstitucional a fim de se investigar gênero, cor da pele, consumo de tabaco e álcool, tamanho dos tumores, metástase regional e à distância, diferenciação histológica e ploidia do DNA dos tumores por meio de citometria por imagem. Os resultados mostraram que tumores em pacientes jovens foram frequentemente detectados em mulheres e pacientes não fumantes e não etilistas, enquanto em pacientes idosos foram detectados, predominantemente, em homens fumantes e etilistas. Além disso, constatou-se que CECs de língua em jovens não se distinguem quanto ao tamanho, a metástases regionais ou à distância e nem quanto ao grau de diferenciação histológica quando comparados com idosos. Ressalta-se, entretanto, que tumores em jovens apresentaram maiores incidências de aneuploidia, tetraploidia e de outros parâmetros de anormalidades da ploidia do DNA. Concluindo, pacientes jovens com CEC de língua apresentaram perfil clínico e biológico peculiares, favorecendo a hipótese de que pacientes jovens com CEC de boca possuem instabilidade genômica aumentada e indicando uma possível natureza genética diferente entre os CECs de língua de jovens e de idosos / Abstract: Oral squamous cell carcinoma (SCC) predominately affects elderly patients and frequently develops in association with tobacco and alcohol consumption. However, an increasing of this malignant disease has been observed in patients younger than 40 years of age, who are not exposed to the traditional risk factors. Data regarding oral cancer in young patients are scarce and controversial, making the determination of the pathogenesis, biological behaviour and prognosis of these tumours difficult. As a consequence, treatment has been mainly based on the professional experience of each medical centre. The aims of this work were to study demographic features, risk factors and clinical aspects at the moment of diagnosis as well as the biologic profile of patients of less than 40 years of age with tongue SCC. A multi-centre retrospective analysis was performed to investigate gender, race, tobacco consumption and alcohol intake, size of the tumour, regional and distant metastasis, histological differentiation and DNA ploidy of tumours through image cytometry. Tumours in young patients were frequently detected in females and nonsmoking and non-drinking patients while older patients were predominantly smoking and drinking males. In addition, tongue SCC in young patients did not differ in size, regional and distant metastasis or tumour grade of differentiation when compared to those in older patients. This study highlighted that tumours from young patients presented higher incidences of aneuploidy, tetraploidy and other parameters related to DNA ploidy abnormalities. In conclusion, young patients with tongue SCC presented a distinct clinical and biological profile, favouring the hypothesis that young patients with oral SCC may have an increased genomic instability and indicating the possibility of underlying genetic differences between TSCC in young and older patients / Doutorado / Patologia / Doutor em Estomatopatologia

O comportamento materno é essencial para a sobrevivência e desenvolvimento do filhote mamífero. Durante a prenhez, as fêmeas recebem estímulos sensoriais e hormonais capazes de modificar e preparar o cérebro da mãe para o início dos padrões de comportamento materno (por exemplo, aumentando o número neurônios produtores de oxitocina no hipotálamo). Estudos têm identificado o hipotálamo como o principal responsável por estas mudanças, porém outras áreas do cérebro também estão envolvidas no processo do comportamento materno. Peg3, um gene marcado paternalmente expresso, é conhecido por controlar o comportamento materno em camundongos. Fêmeas nocautes para o gene Peg3 falham em aumentar a ingestão de alimentos, na ejeção de leite e em algumas atividades maternais, como placentofagia e construção do ninho. Este estudo teve como objetivo determinar os padrões de metilação da região diferencialmente metilada de Peg3 (Peg3DMR) de animais da raça Nelore de bovinos em diversas áreas do cérebro. Amostras foram coletadas das seguintes áreas: córtex frontal, occipital, temporal e parietal, hipocampo e hipotálamo, num total de 8 animais (4 machos e 4 fêmeas). O padrão de metilação destas amostras foi analisado pelo protocolo COBRA (do inglês, Combined Bisulfite-Restriction Analysis), que combina a modificação do DNA por bissulfito de sódio, amplificação por PCR e digestão por enzima de restrição. Foram encontrados diferentes padrões de metilação entre as amostras, ocorrendo uma predominância de hipometilação entre as amostras do sexo masculino, e padrões mais variados nas amostras do sexo feminino. As variações nos padrões de metilação ocorreram de maneira mais marcante entre as amostras de uma mesma região cerebral de diferentes animais, do que entre as amostras de várias regiões de um mesmo animal. Os resultados indicam que pode haver uma variação no status de imprinting em nível populacional, porém estudos com um número maior de amostras são necessários para a verificação da significância estatística destas variações. / The maternal behavior is essential to survival and development of mammalian offspring. Throughout pregnancy, females receive sensory and hormonal stimuli which promote modifications and prepare the mothers brain to the onset of maternal behavior patterns (for example, by increasing numbers of neurons producing oxytocin in the hypothalamus). Studies have identified the hypothalamus as the main responsible for these changes, but other areas of the brain are also involved in the maternal behavior process. Peg3, an imprinted paternally expressed gene, is known to control maternal behavior in mice. Peg3 knockout females failed in increasing food intake, milk ejection and some maternal activities as placentofagia and nest building. This study aimed to determine the methylation patterns of the differently methylated region of Peg3 (DMR-Peg3) of animals from Nellore cattle breed in several areas of the brain. Samples were collected from the following areas of cattle brain: the frontal, occipital, temporal and parietal cortices, hippocampus and hypothalamus, in a total of 8 animals (4 males and 4 females). The methylation pattern of these samples was analyzed by the protocol COBRA (Combined Bisulfite-Restriction Analysis), which combines DNA modification by sodium bisulfite, PCR amplification and digestion by restriction enzymes. It was found different methylation patterns among the samples. There was a predominance of hypomethylation among male samples, while different patterns were found among the female samples. Variation in the methylation patterns was more markedly observed among samples of the same cerebral region among different animals, then among samples of several regions within an animal. The results suggest that there may be a variation in the imprinting status at a population level, but further assays, with an increased number of samples are needed to verify the statistical significance of this variation.

Orientadores: Marcos Antonio Machado, Alexandre Morais do Amaral / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-12T03:30:01Z (GMT). No. of bitstreams: 1 Homem_RafaelAugusto_M.pdf: 2248507 bytes, checksum: 707bfda4edde12e0c0ac988130077aa3 (MD5) Previous issue date: 2008 / Resumo: O cancro cítrico é uma das mais sérias doenças de citros no mundo, sobretudo nos países onde a citricultura exerce papel influente na geração de empregos e divisas, como o Brasil, o maior produtor mundial de laranjas. Por esse motivo, o agente causal dessa doença, a bactéria Xanthomonas axonopodis pv. citri (Xac), teve seu genoma completamente sequenciado. No genoma de Xac foram identificados dois agrupamentos gênicos (operons), xcsCDEFGHIJKLMN e xpsEFGHIJKLMND, que codificam para o sistema de secreção do tipo II (SSTII), mecanismo altamente envolvido no processo de patogenicidade em algumas bactérias causadoras de doenças em plantas. Até o momento, não há evidência da função desempenhada por cada conjunto gênico do SSTII de Xac e da relação desses com o processo de interação com a planta de citros. Neste estudo foram analisadas as funcionalidades dos dois agrupamentos gênicos do SSTII de Xac e sua atividade durante a interação com a planta hospedeira. As análises revelaram que a bactéria utiliza os dois sistemas de forma distinta e com relevância diferenciada durante a interação com a planta, com repercussão no crescimento da bactéria no tecido foliar, sobretudo o operon xps. Adicionalmente, foram identificadas contribuições distintas na atividade de degradação dos compostos amido, carboximetilcelulose e proteína. Exames de microscopia revelaram que a bactéria tem sua organização estrutural do biofilme influenciada pelos dois SSTII e análises de expressão gênica revelaram que o operon xps apresenta atividade extremamente maior em relação ao operon xcs. Estes resultados mostram pela primeira vez a influência independente de ambos SSTII na capacidade patogênica de Xac. / Abstract: The citrus canker is a major threat to the citrus industry worldwide, especially where the citriculture plays an important role in employments and revenues, like United States and Brazil, the largest orange producing country. Therefore, the causal agent of citrus canker, the Gram negative bacterium Xanthomonas axonopodis pv. citri (Xac), had its genome completely sequenced. Throughout the genome of Xac, two operons (xps EFGHIJKLMND and xcsCDEFGHIJKLMN) that encompass 11 and 12 different proteins, respectively, for the type two secretion systems (TIISS) were identified. These mechanisms are highly involved in pathogenicity and virulence in some bacteria that cause disease in plants. However, so far, there are no studies on the function of these operons in Xac and their relationship for the infection process in the citrus plant. In this study, the functions of the two operons that code for the TIISS in Xac and their activity during the interaction with the plant host were analyzed. The analyses revealed that the bacterium uses both TIISS, however in a different fashion during the contact with the leaf tissue and the xps operon is highly more active. In addition, the operons were found to be differentially effective on the degradation of starch, carboxymethilcellulose and proteins. Confocal microscopy investigations found that the bacterial organization (biofilm) is influenced by both TIISS and gene expression analyses showed a much higher activity of the xps operon as compared to the xcs group. These results provide the first clear evidence of the independent influence of both TIISS in the pathogenic process of Xac. / Mestrado / Genetica de Microorganismos / Mestre em Genética e Biologia Molecular

L'intégration et la dégradation des virus (ou phages) au sein des génomes bactériens (alors nommés prophages) constituent un flux de gènes promouvant la diversification génétique de leurs hôtes. Les mécanismes à l'origine de l'impact évolutif des prophages sur leurs hôtes restent cependant mal compris. La première partie de la thèse s'est attachée à comprendre comment les prophages sont adaptés aux contraintes liées à l'organisation génétique et structurelle des chromosomes d'Escherichia et de Salmonella. Ces résultats ont mis en évidence une forte conservation des positions d'intégration des prophages, ainsi que différentes adaptations des phages à l'organisation chromosomique hôte. L'origine de la diversité génétique des phages tempérés a été au centre de la deuxième partie de la thèse. L'étude des phages lambdoïdes a révélé l'existence de deux stratégies de recombinaison chez ces phages: utilisation du système de recombinaison RecBCD de l'hôte via la présence de sites Chi ou utilisation de leur propre système de recombinaison. Ceci suggère que l'utilisation de l'une ou l'autre des stratégies a un impact important sur la diversification et le mosaïcisme génomique phagique. Enfin, la détection et l'analyse de prophages hérités verticalement au sein des génomes hôtes ont montré que de nombreux prophages partiellement dégradés sont conservés et évoluent sous sélection purificatrice. Ces résultats suggèrent que de nombreux prophages sont potentiellement des éléments fonctionnels domestiqués par la bactérie. L'ensemble de ces analyses permet de préciser les mécanismes permettant aux prophages de contribuer à la diversification des répertoires de gènes de leurs hôtes. / The integration and degradation of viruses (or phages) constitute a genetic influx of genes within bacterial genomes (then named prophages). This process is thought to promote bacterial diversification. The mechanisms promoting the evolutionary impact of prophages on their hosts remain poorly understood. The first part of my thesis focused on the adaptation of prophages to the genetic and structural organization of the chromosome of Escherichia and Salmonella. These results showed a strong conservation of prophage integration positions and different adaptations of prophages to the chromosome organization of their hosts. In a second study, I focused on the mechanisms of genetic diversification of phages. The study of lambdoid phages revealed the existence of two recombination strategies among these phages: using the host recombination system RecBCD through the presence of Chi sites or using their own recombination system. This work suggests that using one or the other recombination strategy has an important impact on the genomic diversification and mosaicism of these phages. Finally, by detecting and analyzing vertically inherited prophages within their host genomes, I showed that many degraded prophages are conserved and evolve under purifying selection. This suggests that many prophages are potentially domesticated by bacteria. Altogether, these analyses are improving our understanding of the contribution of prophages to the genetic diversification of their hosts.

Abstract This study was initiated to elucidate the complete genomic structures of type XV collagen in man and mouse and the functional properties of their promoters, as well as to obtain knowledge of the biological role of type XV collagen during development and maturity using immunofluorescence and transgenic techniques. The cloning and characterization of genomic clones revealed that the human COL15A1 gene is 145-kb in size and consists of 42 exons, and the mouse Col15a1 gene is 110-kb with 40 exons. The genomic organization of the two genes was found to be highly conserved, except for two regions of divergence. The nuclease S1 protection analysis revealed multiple transcription initiation sites in both genes, which is in accordance with the overall genomic structures of their 5'-flanking sequences. Transient cell transfection experiments with varying lengths of 5'-deletion constructs identified the fragments necessary for basic promoter activity in both genes and those implicated in the positive and negative regulation of the mouse Col15a1 gene. Furthermore, the involvement of transcription factor Sp1 in the gene regulation of the human COL15A1 gene was demonstrated. A mouse specific polyclonal antibody against type XV collagen was generated and utilized in the localization of type XV collagen protein in developing and mature mouse tissues. Type XV collagen was deposited early in the development and was particularly prominent in capillaries. Spatio-temporal differences in the expression of type XV collagen in various capillary types was demonstrated. Early expression was also detected in the skeletal muscle and peripheral nerves, while expression in the heart, lung, and kidney appeared to be developmentally regulated. Transgenic mice lines expressing truncated type XV collagen driven by either short or long endogenous type XV collagen promoters were generated. The two promoters conferred different tissue-specificities and expression levels, the longer one resulting in more endogenous-like expression. Despite some expression at both mRNA and protein levels, the truncated type XV collagen did not cause any obvious phenotypic or histological changes in any of the lines driven by the shorter promoter fragment. In heterozygote matings of one of the lines driven by the longer promoter fragment, however, a portion of the transgene positive mice appeared to be lost prenatally. Furthermore, pregnancy terminations in this line indicated a high number of abortions beginning at about 11 days of development. Further studies are needed before detailed conclusions on the consequences of the generated mutation can be drawn. The elucidation of the genomic structure of the human COL15A1 gene provides the necessary database for screening mutations in patient samples for candidate diseases caused by this collagen. The genomic clones and the mouse-specific antibody against type XV collagen are valuable tools also in future projects. The knowledge of the developmental dynamics of type XV collagen is of great value, as it helps to understand the physiological consequences that the as yet unidentified mutations in type XV collagen may cause in humans.

Abstract The Prader-Willi (PWS) and Angelman (AS) syndromes are clinically distinct developmental disorders which are caused by genetic defects in the imprinted domain at chromosome 15q11-q13, resulting in the loss of paternal (PWS) or maternal (AS) gene function. In this study, the genetic changes of 15q11-q13 and their possible inheritance in Finnish PWS (n=76) and AS (n=47) patients are described. The diagnosis could be confirmed by laboratory methods in all PWS and in 43 (91%) AS patients. A deletion of 15q11-q13 accounted for 76% of the PWS and 67% of the AS patients in whom a specific genetic defect had been established. The origin of deletion was always paternal in PWS and maternal in AS. In PWS, deletions of four different sizes were detected, while in AS only type I or II deletions were found. The smallest overlap of deletions/critical region detected was from locus D15S13 to locus D15S10 in PWS and from locus D15S128 to locus D15S12 in AS. A rare recurrence of del(15)(q11q13) due to maternal germ line mosaicism is described. Maternal uniparental disomy of chromosome 15 accounted for 21% of PWS patients and paternal UPD for 2% of AS patients. In PWS, most UPD cases were due to errors in maternal meiosis (87%), most commonly leading to maternal heterodisomy (MI error). In AS, a rare error in the second segregation of paternal meiosis was found. UPD was associated with advanced maternal age, the mean being 34.6 years. Imprinting defects were found in 3% of PWS (two non-IC-deletions) and 11% of AS (IC deletion in one sib pair and three non-IC-deletions) patients. In the case with IC deletion, the mutation was seen in several generations. The non-deletion cases were thought to be due to a de novo prezygotic or postzygotic error. In the non-deletion PWS cases, the maternally imprinted paternal chromosome region was shown to have been inherited from the paternal grandmother, while in AS the paternally imprinted maternal chromosome region had been inherited from either the maternal grandfather or the maternal grandmother. The region of IC involved in AS was defined to be 1.15 kb. Five (11%) AS patients with normal DNA methylation test results had a UBE3A mutation. One of the two novel missense mutations (902A→C) had been inherited from the mosaic mother, while the mutation 975T→C was a new one. De novo deletions 1930delAG and 3093delAAGA have also been described previously, suggesting that these sites may be mutation hotspots in UBE3A. Identification of different genetic aetiologies with different recurrence risks is essential for genetic counselling, and close co-operation between clinicians and the laboratory is required both for diagnosis and for the detection of possible inheritance.

L'objectif de ce travail de thèse était d'évaluer l'intérêt de mettre en place des évaluations génomiques dans les programmes de sélection porcins. Des simulations stochastiques ont été réalisées dans le cas d'un programme de sélection d'une lignée mâle de grande taille contenant 1 050 femelles reproductrices et 50 verrats, sélectionnée pendant 10 ans pour améliorer un objectif de sélection combinant 2 caractères, respectivement mesurés sur 13 770 candidats par an (Car1) et sur 270 collatéraux par an (Car2) issus de 10% des portées. Dans la situation de référence, les valeurs génétiques étaient estimées selon la méthodologie du BLUP-Modèle Animal (BLUPMA). Dans une première étude, nous avons comparé le scénario BLUPMA à un scénario génomique dans lequel tous les candidats étaient génotypés. Les évaluations génomiques s'appuyaient sur deux populations de référence (PR) initialement constituées de 13 770 candidats pour Car1 et de 1 000 collatéraux pour Car2, et dont les tailles respectives augmentaient annuellement, en considérant les mêmes capacités de phénotypage que dans le scénario BLUPMA. Les résultats montrent que des évaluations génomiques améliorent nettement la précision d'estimation des valeurs génétiques des candidats pour les deux caractères et le progrès génétique réalisé annuellement sur l'objectif global de sélection (+27% à +33% selon les héritabilités considérées), tout en réduisant significativement l'augmentation de la consanguinité dans la population. Un second scénario génomique a été simulé, dans lequel les candidats n'étaient plus phénotypés et les évaluations génomiques s'appuyaient sur une PR uniquement constituée de collatéraux phénotypés pour Car1 et Car2. Dans ce cas, la précision des valeurs génomiques estimées et la réponse à la sélection pour Car1 sont nettement plus faibles que dans le scénario BLUPMA, montrant que la sélection génomique ne permet pas de mettre fin au phénotypage des animaux. La mise en place d'évaluations génomiques nécessitant de génotyper un grand nombre d'individus, elle entraîne un surcoût important par rapport au scénario BLUPMA. Dans une seconde étude, nous avons montré que ce surcoût peut être largement réduit en présélectionnant les candidats à génotyper sur la base de leur valeur génomique estimée sur ascendance. Il est ainsi possible de réduire de manière significative le nombre de candidats à génotyper tout en préservant une grande partie de l'avantage de la sélection génomique par rapport à la sélection conventionnelle BLUPMA. Ainsi, une diminution de 40% du nombre de candidats génotypés ne réduit que de 3 à 4% le progrès génétique annuel sur l'objectif global. Nous avons également montré qu'au-delà d'un certain seuil d'investissement, une dépense supplémentaire pour améliorer l'efficacité du programme de sélection est plus efficacement investie dans la mise en place d'évaluations génomiques que dans l'augmentation de la capacité de phénotypage des collatéraux dans le dispositif conventionnel. Ce seuil d'intérêt de mise en place d'un programme génomique est d'autant plus bas que le coût du génotypage est faible et que le coût de phénotypage des collatéraux est élevé. L'ensemble de nos résultats suggère qu'il serait intéressant de mettre en place des évaluations génomiques dans un programme de sélection d'une lignée porcine mâle de grande taille, notamment dans la population Piétrain collective française, dont la structure est proche de celle de la population simulée dans nos études. / The aim of this work was to evaluate the interest of implementing genomic evaluations in pig breeding schemes. Stochastic simulation was used. The simulated population was a pig sire line containing 1,050 breeding females and 50 boars. The line was selected for 10 years for a breeding goal including two uncorrelated traits, recorded on, respectively, 13,770 candidates per year (trait1) and 270 relatives per year born in 10% of the litters (trait2). In the reference breeding scheme (BLUPAM), the selection was based on pedigree-based BLUP estimated breeding values (EBVs). In a first study, we compared the BLUPAM scenario to an alternative genomic breeding scheme with the same phenotyping capacities, where all candidates for selection were genotyped. The genomic breeding values for trait1 and trait2 were estimated using two training populations (TP). The first one (TP1) was made up of selection candidates (phenotyped for trait1) and the second one (TP2) of relatives phenotyped for trait2. The size of TP1 and TP2 increased, respectively, from 13,770 to 55,080 and from 1,000 to 3,430 over time. Our results show that genomic evaluations significantly improve the accuracy of the EBVs of the candidates for both traits and therefore the annual genetic trends for the global breeding goal (+27% to +33% depending on trait heritability), while significantly reducing the inbreeding rate. A second genomic scenario was simulated, in which the candidates were no longer phenotyped for trait1, and the genomic breeding values were estimated with one single TP made up of relatives phenotyped for both traits. In that case, the accuracy of EBVs and the annual genetic trends for trait1 are significantly lower than in the reference (BLUPAM) scenario. This shows that a large TP is required to outperform the current schemes for traits recorded on the candidates. The implementation of genomic evaluations requires the genotyping of a large number of animals, and therefore generates additional costs compared to BLUPAM breeding schemes. In a second study, we showed that genotyping a subset of candidates that have been pre-selected according to their parental EBV allows to significantly reduce the extra costs of a genomic breeding scheme while preserving most of its superiority in terms of genetic trends and inbreeding over the BLUPAM breeding scheme. For instance, reducing the number of genotyped candidates by 40% only reduced by 3 to 4% the global annual genetic trend. We also showed that even a very marked increase in the number of relatives phenotyped for trait2 in a BLUPAM scenario does not allow to be as efficient as a genomic scenario when the number of genotyped candidates is large. Finally, we showed that the economic interest of genetic selection can be characterized by an additional cost threshold; below this threshold, it is preferable to maintain pedigree-based BLUP evaluations and increase the number of relatives, while implementing genomic evaluation is more efficient above this threshold. The value of this threshold depends on the cost of phenotyping additional relatives and on genotyping costs.Our results suggest that implementing genomic evaluations in a large size pig sire line can be a valuable strategy. This strategy could for instance easily be applied to the French Piétrain population, which resembles the nucleus population simulated in this study.

Investigating secondary contact of historically isolated lineages can provide insight into how selection and drift influence genomic divergence and admixture. Here, we studied the genomic landscape of divergence and introgression following secondary contact between lineages of the Western Diamondback Rattlesnake (Crotalus atrox) to determine whether genomic regions under selection in allopatry also contribute to reproductive isolation during introgression. We used thousands of nuclear loci to study genomic differentiation between two lineages that have experienced recent secondary contact following isolation, and incorporated sampling from a zone of secondary contact to identify loci that are resistant to gene flow in hybrids. Comparisons of patterns of divergence and introgression revealed a positive relationship between allelic differentiation and resistance to introgression across the genome, and greater-than-expected overlap between genes linked to lineage-specific divergence and loci that resist introgression. Genes linked to putatively selected markers were related to prominent aspects of rattlesnake biology that differ between populations of Western Diamondback rattlesnakes (i.e., venom and reproductive phenotypes). We also found evidence for selection against introgression of genes that may contribute to cytonuclear incompatibility, consistent with previously observed biased patterns of nuclear and mitochondrial alleles suggestive of partial reproductive isolation due to cytonuclear incompatibilities. Our results provide a genome-scale perspective on the relationships between divergence and introgression in secondary contact that is relevant for understanding the roles of selection in maintaining partial isolation of lineages, causing admixing lineages to not completely homogenize.

>Magister Scientiae - MSc / The generation of biomedical research data on the African continent is growing, with numerous studies realizing the importance of African genetic diversity in discoveries of human origins and disease susceptibility. The decrease in costs to purchase and utilize such tools has enabled research groups to produce datasets of significant scientific value. However, this success story has resulted in a new challenge for African Researchers and institutions. An increase in data scale and complexity has led to an imbalance of infrastructure and skills to manage, store and analyse this data