Nos programas de melhoramento de cana-de-açúcar todos os anos são instalados experimentos com o objetivo de avaliar genótipos que podem eventualmente ser recomendados para o plantio, ou mesmo como genitores. Este objetivo é atingido com o emprego de experimentos em diferentes locais, durante diferentes colheitas. Além disso, frequentemente há grande desbalanceamento, pois nem todos os genótipos são avaliados em todos os experimentos. O emprego de abordagens tradicionais como análise de variância conjunta (ANAVA) é inviável devido à condição de desbalanceamento e ao fato de as pressuposições não modelarem adequadamente o relacionamento entre as observações. O emprego de modelos misto utilizando a metodologia REML/BLUP é uma alternativa para análise desses experimentos em cana-deaçúcar, permitindo também incorporar a informação de parentesco entre os indivíduos. Nesse contexto, foram analisados 44 experimentos (locais) de cana-de-açúcar do programa de melhoramento da cana-de-açúcar do Instituto Agronômico de Campinas (IAC), com 74 genótipos (clones e variedades) e com até 5 colheitas. O delineamento foi o de blocos ao acaso com 2 a 6 repetições. O caráter analisado foi TPH (Tonelada de pol por hectare). Foram testados 40 modelos, os 20 primeiros foram avaliadas diferentes estrutura de VCOV para locais e colheitas, e os 20 seguintes, além das matrizes de VCOV, foi incorporada a matriz de parentesco genético, A. De acordo com AIC, verificou-se que o Modelo 11, o qual assume as matrizes FA1, AR1 e ID, para locais, colheitas e genótipos, respectivamente, foi o melhor, e portanto, o mais eficiente para seleção de genótipos superiores. Quando comparado ao modelo tradicional (médias dos experimentos), houve mudanças no ranqueamento dos genótipos. Há correlação entre o modelo tradicional e o Modelo 11 (_ = 0, 63, p-valor < 0, 001). A opção de utilizar modelo misto sem ajustar as matrizes de VCOV (Modelo 1) é relativamente melhor do que usar o Modelo Tradicional. Isto foi evidenciado pela correlação mais alta entre os modelos 1 e 11 (_ = 0, 87 com p-valor < 0, 001). Acredita-se que o emprego do Modelo 11 junto com experiência do melhorista poderá aumentar a eficiência de seleção em programas de melhoramento de cana-de-açúcar. / In breeding programs of sugarcane every year experiments are installed to evaluate the performance of genotypes, in order to select superior varieties and genitors. The use of ordinary approaches such as joint analysis of variance (ANOVA) is unfeasible due to unbalancing and assumptions that do not reflect the standard of relationship of the observations. The use of mixed models using the method REML/BLUP is an alternative. It also allows the incorporation of information from kinship between individuals. In this context, we analyzed 44 trials (locations) of sugarcane breeding program of sugarcane (Agronomic Institute Campinas, IAC), with 74 genotypes (varieties and clones), up to 5 harvests. The experimental design was randomized blocks with 2-6 replicates. The character was examined TPH (Tons of pol per hectare). We tested 40 models, the first 20 were evaluated different VCOV structure to locations and harvests, and 20 following addition of matrix VCOV was incorporated genetic relationship matrix, A. Under AIC, it was found that the model 11, which assumes matrices FA1, AR1 and ID for locations, harvests and genotypes, respectively, was the best. There is a moderate correlation between traditional model and model 11 (_ = 0.63, p-value < 0.001), when ranking the genotypes. The option of using mixed model without adjusting matrices VCOV (model 1) is better than using the traditional model. This was suggested by the higher correlation between models 1 and 11 (_ = 0.87 with p-value < 0.001). We believe that the usage of model 11 together with breeders experience can increase the efficiency of selection in sugarcane breeding programs.

Understanding the degree of connectivity among populations, forming migratory links and evaluating factors that influence reproductive fitness is fundamental for the successful management of migratory species of conservation concern. In this thesis I focus on a regionally important rookery of green turtles (Chelonia mydas) at Alagadi beach in northern Cyprus that has been intensively studied since 1992. I employ high resolution genetic markers with different modes of inheritance to reveal fine scale population structuring among four rookeries within a 200 km stretch of shoreline. The relative importance of four foraging areas and the annual contribution from each site to the breeding cohort are evaluated using the stable isotope ratios of the turtles calibrated by satellite telemetry. The stable isotope ratios of the turtles reveal that a previous undisclosed foraging site at Lake Bardawil in Egypt is critical for the population recovery of the Alagadi rookery. The temporal consistency of stable isotope ratios reaffirm that green turtles exhibit high fidelity to foraging sites allowing the evaluation of foraging area effects on reproductive traits to be evaluated over multiple seasons. I investigate the population sub-structuring of the Alagadi nesting aggregation grouped by the foraging area used. The absence of genetic structure supported the Learning Migration Goal Theory and provided evidence that the significant among site phenotypic variability in the body size of recruits, the length of interbreeding intervals and the date that the first nest of the season was made is a result of foraging areas effects. No significant among site phenotypic variability was found for the size or number of clutches laid. Among site variability in interbreeding intervals resulted in substantial variation in the reproductive potential of individuals due to assumed differences in resource availability and environmental factors. The multilocus genotypes generated for 243 nesting females were employed to reconstruct the first wild marine turtle pedigree using a full-likelihood sib-ship reconstruction approach. This revealed that the effective contribution to the next generation was unequal and allowed a minimum age to maturity to be estimated from parent – offspring assignations. However, sample size constraints prevented accurate estimates for the narrow-sense heritability of the five morphological and life-history traits from the quantitative genetic analysis. The multifaceted approach taken here to unravel the cryptic life-history of marine turtles emphasises the importance of long-term individual-based monitoring and the data generated can be employed to advise conservation strategy for this critically endangered regional management unit.

Le potentiel évolutif des populations naturelles à répondre aux changements environnementaux détermine leur capacité à s'adapter et à survivre. Pour achever une évolution adaptative, la fitness doit être héritable, i.e. doit être transmise des parents à leurs descendants par des gènes. Pour pouvoir mesurer le potentiel évolutif d'une population en milieu naturel, il est primordial d'avoir au préalable des informations sur la fitness des individus qui la composent, mais aussi de connaître la fitness de leurs descendants. Les mesures de fitness sont extrêmement rares, en particulier pour les espèces marines, où les relations entre les générations sont rarement connues. Dans cette thèse, je présente le premier pedigree construit pour une population de poissons marins sur la base du suivi génétique mené depuis plus de 10 ans sur les poissons-clowns orange de l'île de Kimbe (Papouasie-Nouvelle Guinée). Le pédigrée comprend 2927 individus et révèle une philopatrie natale sur 5 générations. L'approche en génétique quantitative révèle que la fitness locale a une très faible valeur d'héritabilité (<1%). La variation génétique additive et les effets maternels sont également très faibles (<1%). En revanche, l'habitat est le principal facteur qui explique les différences de fitness locale observées entre les individus (jusqu'à 96,5%). Ensemble, ces résultats suggèrent que, bien que l'environnement impose une forte pression de sélection sur la fitness locale, la population de poissons-clowns orange a un très faible potentiel d'évolution face aux changements environnementaux. / The evolutionary potential of wild populations to respond to environmental change will determine their capacity to adapt and survive. However, in order to achieve evolutionary change, variation in the contribution of an individual to the next generation — its fitness — must have a genetic basis and be heritable. The study of the evolutionary potential of populations requires longitudinal and relatedness data with different environments to partition the contribution of genes, maternal effects and environment on fitness. Estimates of genetic heritability of fitness traits are extremely rare, especially for marine species, where inter-generational relationships are rarely known. Here, we present the first multi-generational pedigree for a marine fish population by repeatedly genotyping all individuals in a population of the orange clownfish (Amphiprion percula) at Kimbe Island (Papua New Guinea) over a 10-year period. Based on 2927 individuals, our pedigree analysis revealed that longitudinal philopatry was recurrent over five generations. We show that local reproductive success has a very low (<1%) but significant heritability. We also show that additive genetic variation and maternal effects on local fitness are both extremely low (<1%). Habitat is the major driver that explain differences in the contribution of individuals to the next generation in the local population (until 96.5%). Together these results suggest that while the environment imposes strong selection pressures on the local fitness, the low heritability indicates the orange clownfish population has little evolutionary potential to adapt to local environmental changes.

This thesis examines how the ethics of caring for pedigree dogs differ in the contexts of dog showing and veterinary practice. By highlighting conflicts around the shared use of ‘ordinary language’, I show how tensions between show‐world and veterinary perspectives relate to divergent understandings of ‘health’. Canine bodies speak to vets and breeders in conceptually different ways, so much so that breed‐specific features can be considered ‘perfect’ in the show‐ring yet ‘pathological’ in the veterinary clinic. Developing the emergent anthropological perspective that care is both a moral and an embodied practice, I argue that the qualities of moral virtue and aesthetic virtu are inextricably linked in the care practices by which breeders aim to produce and sustain canine bodies in their idealised forms. Also fundamental to show‐world notions of care is the understanding that care for dog and care for breed are one and the same. In sharp contrast, veterinary practice attends to dogs as individuals rather than members of breeds. Here, I examine how breeders and vets respond to the multiple and conflicting demands of caring for pedigree dogs in the course of encounters often fraught with unresolved tension. Asking how seemingly irreconcilable notions of what counts as good health play out in these negotiations, I argue that care can depend on the ability to transcend – or at least overlook – different ethical orientations. In practice, I argue that negotiations between breeders and vets are often non‐verbal and based on a mutual understanding that the ability to work together in performing care relies not only on clear communication but, at times, on a knowing silence. Under ever‐increasing pressure to engage with veterinary notions of health, many show‐breeders now deem ignorance of veterinary knowledge – and silence in the face of disease – ethically virtuous. I therefore conclude that deliberate silence and selective ignorance enable breeders and vets to temporarily reconcile their different understandings of what is good, thus allowing both parties to meet their respective responsibilities of care.

Although the captive reproduction of non-avian reptiles has increased steadily since the 1970’s, a dearth of information exists on successful management practices for large captive populations of these species. The data reported here come from a captive population of ball pythons (Python regius) maintained by a commercial breeding company, The Snake Keeper, Inc. (Spanish Fork, UT). Reproductive data are available for 6,480 eggs from 937 ball python clutches. The data presented suggest that proper management practices should include the use of palpation and/or ultrasound to ensure breeding occurs during the proper time of the female reproductive cycle, and that maintenance of proper humidity during the incubation of eggs is vitally important. Ball python reproduction traits (clutch size, clutch mass, relative clutch mass, egg mass, hatch rate, egg length, egg width, hatchling mass, healthy offspring per clutch, week laid, and days of incubation) were recorded for the clutches laid during this study. For the 937 clutches, the identity of the dam and sire were known for 862 (92%) and 777 (83%) of the clutches, respectively. A multivariate model that included nine of the 11 traits listed above was compiled. Heritability and genetic and phenotypic correlations were calculated from the multivariate analysis. The trait that showed the most promise for use in artificial selection to increase reproduction rates was clutch size due to considerable genetic variation, high heritability, and favorable genetic correlations with other reproduction traits. Although large datasets have been published for twinning in avian species, relatively few are available for non-avian reptiles. Reported here are 14 sets of twins produced from 6,480 eggs from 937 ball python clutches. The survival rate for twins during the first 3 months of life in our study was 97%. Interestingly, 11 of the sets of twins were identical in sex and phenotype, and additional genetic data suggested the rate of monozygotic twinning within this captive population of ball pythons was higher than that of dizygotic twinning. Further, using microsatellite analysis we were able to generate data that shows three sets of python twins were genetically identical.

L'objectif de cette thèse est double : examiner en détails d'une part, les liens entre les différents critères obtenus à partir de différents types d'information, tels que les marqueurs moléculaires, les pedigrees ou les phénotypes des caractères quantitatifs, et d'autre part, l'évolution conjointe de la variabilité neutre et de la variabilité sélectionnée. En fonction de la nature des informations, la variabilité génétique et son évolution sont décrites par différents paramètres qui s'appuient sur des modèles sous-jacents plus ou moins complexes et la représentation qu'on se fait de la diversité génétique sera donc plus ou moins réaliste. Ainsi, l'analyse du polymorphisme nous donne directement une image précise de la diversité au niveau du génome. Par exemple, les génotypes et les fréquences alléliques de gènes candidats, ou plus généralement de marqueurs moléculaires, nous donnent directement accès au polymorphisme spécifique à des gènes identifiés en des endroits précis du génome ; quant aux analyses basées sur les pedigrees, elles traduisent le polymorphisme en un locus neutre et anonyme, n'importe où dans le génome. Par contre, l'analyse des phénotypes nécessite des modèles de représentation plus complexes et nous une vue d'ensemble générale de la diversité génétique. Les principales méthodes pour l'analyse de la diversité génétique à partir d'informations de natures différentes, et celles utilisées au cours de cette thèse, sont présentées dans le premier chapitre. Les chapitres 2, 3 et 4 constituent une valorisation des différents types d'informations issues de lignées expérimentales de poulets sélectionnées pour des critères de réponse immunitaire. L'ensemble de ces analyses constitue une analyse intégrée de la diversité génétique. Dans le chapitre 2, nous analysons la diversité génétique et le gain génétique, sur la base des performances et des données généalogiques. Les valeurs observées de consanguinité et de gain génétique sont confrontées à des valeurs prédites à partir de modèles théoriques : les méthodes déterministes ont permis d'obtenir des valeurs prédictives proches des valeurs observées, les différences étant principalement dues à l'écart entre les hypothèses sur le schéma de sélection et la réalité, et les simplifications mathématiques faites dans les modèles de prédiction. Nous avons également testé l'effet du schéma de sélection sur la consanguinité et les autres critères de diversité génétique obtenus à partir des généalogies. Le nombre efficace d'ancêtres s'est révélé être le paramètre le plus pertinent pour suivre l'évolution de la diversité génétique puisqu'il prend en compte la perte de diversité qui a lieu au cours des générations sous l'effet de la dérive génétique. L'estimation des paramètres génétiques et leur évolution sont présentées au chapitre 3, ainsi que l'évolution du polymorphisme d'un gène candidat. Afin de tester la neutralité du CMH sur les caractères de nos lignées sélectionnées, nous avons analysé les composant de la variance et avons également comparé l'évolution du polymorphisme dans les lignées avec l'évolution théoriques issues de modèles de prédiction. Au-delà de la mise en évidence de l'effet du CMH dans la réponse immunitaire, cette étude a permis de souligner l'intérêt de combiner différentes approches afin de juger de l'effet d'un gène candidat, et de son évolution, et ce plus particulièrement quand ce gène présente des allèles rares. Nous avons également examiné les variations de la diversité génétique additive au cours du temps, en tentant de surmonter les difficultés pour estimer les paramètres génétiques liées au modèle théorique sous-jacent (modèle polygénique infinitésimal). Pour cela, nous avons testé l'augmentation du nombre de générations disponibles pour l'analyse par REML, et l'utilisation de l'information de quelques générations seulement ; ces approches se sont avérées satisfaisantes pour observer l'évolution de la variance génétique additive et inférer sur l'effet de la sélection sur la réduction de la variance génétique additive. Dans le chapitre 4, nous avons analysé et comparé l'évolution du polymorphisme de marqueurs moléculaires supposés neutres ou soumis à sélection. Afin de mettre en évidence la signature de sélection laissée par les QTL, nous avons combiné différentes méthodes, simulations et méthodes statistiques. L'étude a montré l'intérêt de comparer l'image de la diversité génétique définie par le polymorphisme de marqueurs situés dans des zones QTL à celle définie par le polymorphisme des marqueurs supposés neutres. Au travers des différents chapitres, la modélisation est apparue comme une approche efficace pour prédire l'évolution des populations sélectionnées, même si les hypothèses de modélisation faites (telles que le model additif polygénique, la normalité des distributions ou la population des fondateurs sous équilibre de Hardy-Weinberg, etc.) ne correspondent pas exactement au réel modèle biologique. La taille efficace de la population (Ne) est un paramètre clé dans l'estimation de la variabilité génétique que nous avons estimé dans les lignées expérimentales de poulets, soit à partir des généalogies, soit à partir des variations des fréquences alléliques. Il est apparu que les estimations faites à partir des généalogies étaient toujours inférieures aux estimations faites à partir des fréquences alléliques, quelque soit le type de locus considéré (gène candidat, markers supposé neutre ou soumis à sélection). L'estimation de Ne à partir des fréquences alléliques des marqueurs neutres a donné une valeur plus faible que celle à partir des fréquences alléliques des marqueurs soumis à sélection. Ceci nous permet de dire que la diversité génétique est plus réduite dans les régions soumises à sélection que dans le reste du génome. Au chapitre 5, nous n'avons pas analysé la diversité génétique en elle-même mais les conséquences d'une réduction de cette diversité génétique. L'étude a porté sur anomalies génétiques dans les populations ayant subi un fort goulot d'étranglement, telles que la population française bovine laitière Prim'Holstein. Nous avons montré que l'origine des pics de veaux mort-nés venait du très faible nombre de pères et de leur utilisation non équilibrée. Nous avons aussi examiné les conséquences, à court terme et à long terme, d'une contre sélection exercée sur l'allèle délétère responsable d'une anomalie.

In instances of mass fatality, such as plane crashes, natural disasters, or terrorist attacks, investigators may encounter hundreds or thousands of DNA specimens representing victims. For example, during the January 2010 Haiti earthquake, entire communities were destroyed, resulting in the loss of thousands of lives. With such a large number of victims the discovery of family pedigrees is possible, but often requires the manual application of analytical methods, which are tedious, time-consuming, and expensive. The method presented in this thesis allows for automated pedigree discovery by extending Link Discovery Tool (LDT), a graph visualization tool designed for discovering linkages in large criminal networks. The proposed algorithm takes advantage of spatial clustering of graphs of DNA specimens to discover pedigree structures in large collections of specimens, saving both time and money in the identification process.

Schizophrenia is one of our most common psychiatric diseases. It severely affects all aspects of psychological functions and results in loss of contact with reality. No cure exists and the treatments available today produce only partial relief for disease symptoms. The aim of this work is to better understand the etiology of schizophrenia by identification of candidate genes and gene pathways involved in the development of the disease. In a preliminarily study, the effects of medication and genetic factors were investigated in a candidate gene, serotonin 2C receptor. This study distinguished pharmacological effects, caused by neuroleptics, and/or genetic effects, caused by unique polymorphisms, from other effects responsible for mRNA expression changes on candidate genes. The core of the thesis describes a new candidate gene for schizophrenia, the quaking homolog, KH domain RNA binding (mouse) or QKI, located on chromosome 6q26-q27. The identification of QKI is supported by previous linkage studies, current association studies and mRNA expression studies using three different sample sets. The investigated samples included a 12-generation pedigree with 16 distantly related schizophrenic cases and their parents, 176 unrelated nuclear families with at least one affected child in each family and human brain autopsies from 55 schizophrenic cases and from 55 controls. Indirect evidence showing involvement of QKI in myelin regulation of central nervous system is presented. Myelin plays an important role in development of normal brains and disruption of QKI might lead to schizophrenia symptoms. In a forth sample set, including extended pedigrees originated from a geographically isolated area above the Arctic Circle, in northeast Sweden, two additional schizophrenia susceptibility loci were identified, 2q13 and 5q21. Both these regions have previously been highlighted as potential schizophrenia loci in several other investigations, including a large Finnish study. This suggests common schizophrenia susceptibility loci for Nordic populations. A pilot investigation including a genome wide haplotype analysis is presented. This statistical strategy could be further developed and applied to the artic Swedish families, including analysis of 900 microsatellites and 10,000 SNPs. These findings will facilitate the understanding of the schizophrenia etiology and may lead to development of more efficient treatments for patients that suffer from schizophrenia.

In instances of mass fatality, such as plane crashes, natural disasters, or terrorist attacks, investigators may encounter hundreds or thousands of DNA specimens representing victims. For example, during the January 2010 Haiti earthquake, entire communities were destroyed, resulting in the loss of thousands of lives. With such a large number of victims the discovery of family pedigrees is possible, but often requires the manual application of analytical methods, which are tedious, time-consuming, and expensive. The method presented in this thesis allows for automated pedigree discovery by extending Link Discovery Tool (LDT), a graph visualization tool designed for discovering linkages in large criminal networks. The proposed algorithm takes advantage of spatial clustering of graphs of DNA specimens to discover pedigree structures in large collections of specimens, saving both time and money in the identification process.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (p. 156-158).