The Lake Malawi cichlid fishes are a pre-eminent example of adaptive evolutionary radiation. The diversity of species (nearly 1000 extant) is mirrored by an array of variation in dozens of phenotypes (e.g. trophic morphology, tooth shape, color patterns, behavior, development). The unique characteristics of this system have produced unparalleled diversity with very little genetic differentiation between species. This dissertation is composed of four studies addressing different aspects of the variation in the LM cichlids and the mechanisms generating and maintaining this level of diversity at multiple biological levels. Community-level diversity is investigated using null model analysis of species co-occurrence data. We detect signals of non-random community assembly at only the broadest and finest spatial scales. Based on the unique ecological and evolutionary characteristics of this assemblage we suggest that different mechanisms are responsible for these patterns. A core‟ group of species is posited to act as a foundation on which these diverse communities are created as a result of fine-scale species interactions. We identify both positive and negative depth-based correlations between species and suggest these interactions play an important role in species diversity in these fish. The Lake Malawi cichlids exhibit an array of trophic morphologies which may play a role in the fine-scale species interactions described in chapter one. In the second chapter we build a genetic model to predict the evolution of jaw morphology and a complex functional jaw trait. We use a complex biomechanical system, the 4-bar jaw linkage, to simulate trait evolution during interspecific hybridizations. We find rampant transgression (trait values beyond parental distributions) in jaw function in a large proportion of potential crosses. This result is characterized by a lack of novel morphological components but rather is the result of recombinations of existing component traits thus producing functional novelty. In the third chapter we create a laboratory cross of one of the parental combinations suggested from the genetic model. The results of this study serve as a proof of principle to the simulations as we observe a large proportion of transgressive 4-bar function in the F2. As predicted this diversity is produced in the absence of transgressive morphology. We contrast these results between this complex system and data generated from several simple jaw lever traits and report differences in the patterns. Using quantitative trait locus (QTL) mapping approaches we examine the genetic basis for complex and simple jaw traits and discuss correlative patterns within and between systems. Finally we examine the genetic architecture of sex-determination and color morphs in this hybrid cross. We find both ZW and XY sex systems segregating as well as linkage to sex-specific color patterns. Several loci and epistatic interactions are associated with sex-determination and color morphs in this cross. The orange-blotch (OB) color is found associated with ZW as predicted from previous work but a previously undescribed (in these species) male nuptial color (blue) is found associated with both ZW and XY genetic systems as well as other loci segregating for sex-determination. These results are discussed in the context of models of sex chromosome evolution as a result of sexual conflict and the potential importance of sexual selection in the diversification of Lake Malawi cichlids. Overall we observe various mechanisms generating and maintaining diversity at different levels of biological organization. We use community co-occurrence analyses, genetic simulation, and QTL analysis of an F2 hybrid population to examine these mechanisms in this rapidly radiating assemblage. These results bolster our understanding of the origins of diversity and the interplay between variation and aspects of evolution in all biological systems.

Copies of author's previously published works inserted. / Bibliography: leaves 321-370. / xv, 370, [21] leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aim of the project presented in this thesis is to isolate microsatellite markers and to construct a high resolution genetic map of the human X chromosome using these and pre-existing microsatellite markers. AC dinucleotide repeat markers are isolated from a bacteriophage library for application to the genetic localisations of X-linked disease genes, particularly those responsible for non-specific mental retardation (MRX). The genetic map is used to refine the location of the disease gene segregating in five families affected with X-linked mental retardation. / Thesis (Ph.D.)--University of Adelaide, Dept. of Genetics, 1997

M.Sc. / The amount of allozyme variation within, and the extent of genetic differentiation between, 19 sheep breeds from southern Africa were determined by six enzyme coding loci. Another eight enzyme coding loci were analyzed for five breeds. Between 55 and 66.67% of the protein coding loci were polymorphic (95% criterion) in all the breeds, except for the Namaqua sheep that were less polymorphic (33.33%). Values of 1.67 to 2.5 were obtained for the mean number of alleles per locus and average heterozygosities per locus was between 16.6 to 35.9%. The allelic constitution particularly at the transferrin (TF) locus varied appreciably for the different breeds. For example, the TF*H allele was exclusively noted in the Dormer sheep and the TF*G allele was found in the Afiino, Van Rooy, Border Leicester, Blackhead Persian and Skilder-Persian breeds. The only polymorphic breeds at the albumin locus were the South African Mutton Merino and Van Rooy breeds. The allelic constitution at the other polymorphic loci was similar for the breeds, but the allele frequencies of the South African Merino differs from Merino breeds in other countries at the TF locus. Unbiased genetic distance values were the smallest between the Dorper and Dormer breeds and the largest between the Romenof and Blackhead Persian breeds, and the mean genetic distance between the 19 breeds was 0.067. The mean amount of differentiation among the breeds relative to ' the limiting amount under complete fixation (F st) was calculated at 0.123, which is an indication of small genetic differentiation between the breeds studied. However, this , statistic is not reflected by the allele distribution that was not identical for 25 breed pairs (15%) of the total (171) at all the genetic blood systems studied. None of the breed pairs showed identical allele distributions at all the loci studied for at least one locus differed at each breed pair compared. Random amplified polimorphic DNA's gave no consistent or repeatable results. The results of the allozyme study presents the first study of the current genetic characterization of the different southern African sheep breeds.

Identifying disease risk genes is a central topic of human genetics. Cost-effective exome and whole genome sequencing enabled large-scale discovery of genetic variations. However, the statistical power of finding new risk genes through rare genetic variation is fundamentally limited by sample sizes. As a result, we have an incomplete understanding of genetic architecture and molecular etiology of most of human conditions and diseases. In this thesis, I developed new computational methods that integrate functional genomics data sets, such as epigenomic profiles and single-cell transcriptomics, to improve power for identifying genetic risks and gain more insights on etiology of developmental disorders. The overall hypothesis that disease risk genes contributing to developmental disorders are bottleneck genes under normal development and subject to precise transcriptional regulations to maintain spatiotemporal specific expression during development. In this thesis I describe two major research projects. The first project, Episcore, predicts haploinsufficient genes based on a large integrated epigenomic profiles from multiple tissues and cell lines by supervised machine learning methods. The second one, A-risk, predicts plausibility of being risk genes of autism spectrum disorder based on single-cell RNA-seq data collected in human fetal midbrain and prefrontal cortex. Both methods were shown to be able to improve gene discovery in analysis of de novo mutations in developmental disorders. Overall, my thesis represents an effort to integrate functional genomics data by machine learning to facilitate both discovery and interpretation of genetic studies of human diseases. We believe that such integrative analysis can help us better understand genetic variants and disease etiology.

Please read the abstract in the section 00front of this document / Dissertation (MSc (Genetics))--University of Pretoria, 2002. / Genetics / unrestricted

Yes / Oxidative genome damage is an unavoidable consequence of cellular metabolism. It arises at gene regulatory elements by epigenetic demethylation during transcriptional activation1,2. Here we show that promoters are protected from oxidative damage via a process mediated by the nuclear mitotic apparatus protein NuMA (also known as NUMA1). NuMA exhibits genomic occupancy approximately 100 bp around transcription start sites. It binds the initiating form of RNA polymerase II, pause-release factors and single-strand break repair (SSBR) components such as TDP1. The binding is increased on chromatin following oxidative damage, and TDP1 enrichment at damaged chromatin is facilitated by NuMA. Depletion of NuMA increases oxidative damage at promoters. NuMA promotes transcription by limiting the polyADP-ribosylation of RNA polymerase II, increasing its availability and release from pausing at promoters. Metabolic labelling of nascent RNA identifies genes that depend on NuMA for transcription including immediate-early response genes. Complementation of NuMA-deficient cells with a mutant that mediates binding to SSBR, or a mitotic separation-of-function mutant, restores SSBR defects. These findings underscore the importance of oxidative DNA damage repair at gene regulatory elements and describe a process that fulfils this function.

Capes / A respectiva pesquisa encontra-se no contexto de um ciclo produtivo de um laboratório de análises clínicas da área genômica. Esse trabalho propôs um método de redução de dimensionalidade que auxilia o diagnóstico para a medicina laboratorial genômica. O novo método de redução de dimensão de dados é chamado de DRM-F e é capaz de identificar em bases deste domínio os atributos (gene) mais relevantes, por meio de conceitos de equivalência e generalização. Foi efetuada a comparação do Método DRM-F com o Método de Seleção de Atributos. Essa comparação objetivou a avaliação do método proposto com o método já existente na mineração de dados, Seleção de Atributos. O Método DRM-F fundamentado em Framework usou conceitos de equivalência e generalização. Esses dois métodos foram aplicados no domínio de expressão de genes usando três bases, denominadas DLBCL, DLBCL Tumor sobre leucemia e ALL/AML contendo dados do linfoma. Analisando os resultados obtidos, utilizando como critérios de avaliação a Validação Cruzada, verificou-se que o uso dos métodos resultou em uma melhora nos valores de taxa de acerto quando comparados com as bases, possuindo todos os atributos no domínio de expressão gênica. Nesse domínio, o melhor método de redução foi com o uso da Abordagem Wrapper nas três bases. Não obstante, ressalta-se que o método proposto apresentou um resultado superior a 80% de taxa de acerto, não podendo ser considerado um método de redução com desempenho ruim. O Método DRM-F, embora tenha apresentado resultados inferiores ao método de Seleção de Atributos, na média geral não apresentou taxa de acerto inferior a 80% na geração de modelos preditivos. O Método DRM-F busca extrair os atributos (gene) comuns e específicos do domínio de estudo, expressão gênica, porém não somente de uma única base, mas, entre todas as bases que pertencem ao domínio. Assim, podem-se obter os atributos (gene) comuns entre as várias doenças analisadas entre as bases. No presente experimento, foi possível extrair os atributos (gene) comuns e específicos entre as doenças analisadas. Com os atributos (gene) comuns e específicos de cada doença, podem-se submeter esses subconjuntos a uma análise biológica, a fim de verificar o significado biológico dos atributos objetivando uma contribuição na área biomédica e direcionamento de diagnósticos. / The following research is in the context of a production cycle of a clinical laboratory in the genomic area. This work proposed a dimensionality reduction method that helps the diagnosis for the genomic laboratory medicine. The new method of data size reduction is called DRM-F and it is able to identify on bases of this domain the most relevant (gene) attributes, by means of equivalence and generalization concepts. The DRM-F Method was compared to the Attributes Selection Method. This comparison aimed to assess the proposed method with the existing method for data mining, Attributes Selection. In the DRM-F Method based on Framework used equivalence and generalization concepts. These two methods have been applied in the domain of gene expression using three bases, named DLBCL, DLBCL tumor regarding leukemia and ALL/AML containing lymphoma data. Analyzing the results, using as assessment criteria the Cross Validation, it was found that the use of the methods resulted in an improvement in the hit ratio values as compared with bases having all the attributes in the domain of gene expression. In this area the best reduction method was achieved by using the wrapper approach in the three bases. Nevertheless, it is noteworthy that the proposed method showed a result of over 80% in accuracy rate, which cannot be considered a reduction method with poor performance. Although the DRM-F Method presented results below the attributes selection method, in general it showed no average hit rate lower than 80% in the generation of predictive models. The DRM-F Method, aims to extract common and specific (gene) attributes from the field of study, gene expression, but not only from a single base, but among all the bases belonging to the domain. Thus, one can obtain the (gene) attributes common among the various diseases analyzed between the bases. In the present experiment, it was possible to extract the common and specific (gene) attributes among the analyzed diseases. With the (gene) attributes common and specific to each disease it is possible to submit these subsets to biological analysis in order to verify the biological significance of the attributes with the objective of contributing to the area of biomedical diagnostics and routing.

O objetivo deste estudo foi estimar parâmetros genéticos relacionados ao peso à emergência, comprimento corporal, comprimento e largura do abdome, peso, diâmetro e volume de espermateca e peso dos ovários de rainhas Apis mellifera L. (Hymenoptera: Apidae) africanizadas. Os dados analisados se referem a pesagem corporal e medidas do comprimento e largura do abdome de 1056 rainhas, mensurações do comprimento corporal de 102 rainhas, peso da espermateca de 830 rainhas, diâmetro e volume da espermateca de 813 rainhas e peso dos ovários de 970 rainhas, totalizando 1133 animais na matriz de parentesco. Os efeitos fixos considerados foram família, época e mini-recria e os efeitos aleatórios, o genético aditivo e o resíduo. As análises foram realizadas por meio da inferência Bayesiana utilizando o modelo animal. Foram realizadas análises unicarater e bicarater para todas as características. Em análise unicarater, a proporção da variância genética aditiva foi responsável por mais de 50% da variância fenotípica total e as herdabilidades apresentaram estimativas de magnitudes médias a altas para todas as características, sendo 0,46 para peso à emergência, 0,59 para comprimento do abdome, 0,56 para largura do abdome, 0,80 para comprimento corporal total, 0,62 para peso da espermateca, 0,55 para diâmetro da espermateca, 0,64 para volume da espermateca e 0,62 para peso dos ovários. Correlações genéticas favoráveis de magnitudes entre 0,46 a 0,86 foram encontradas para as associações entre peso à emergência, comprimento corporal e comprimento e largura do abdome. Quando avaliadas as relações entre peso à emergência, comprimento corporal e comprimento e largura do abdome com peso, diâmetro e volume de espermateca e peso dos ovários, a maior correlação genética foi entre peso à emergência e peso dos ovários de 0,49. Correlação genética de 0,46 foi encontra para peso à emergência e comprimento do abdome, 0,86 para peso à emergência e largura do abdome e 0,70 para peso à emergência e comprimento corporal. Todas as características avaliadas em análise unicarater apresentam potencial de seleção e, as correlações genéticas entre o peso da rainha à emergência e características da espermateca e peso dos ovários são determinados, em parte, pelo mesmo conjunto de genes, indicando que essas associações podem ser utilizadas em programas de melhoramento genético de abelhas africanizadas, visando o maior potencial reprodutivo de rainhas A. mellifera africanizadas. / The objective of this study was to estimate the genetic parameters the weight at emergence, body length, length and width of abdomen, weight, diameter and volume the spermathecae and weight of ovaries of queen bees Apis mellifera L. (Hymenoptera: Apidae) africanized. The data analysed refer to weighing the body and length and width of abdomen measures of 1056 queen bees, measurements of body length the of 102 queen bees, weight of spermathecae of 830 queen bees, diameter and volume of spermathecae of 813 queen bees and weight of ovaries of 970 queen bees, amounting 1133 animals in the matrix parentage. The effects fixed considered were family, epoch and mini-recreates and the random effects, genetic aditive and the residual. The analyses realized were through the inference Bayesian using the animal model. Were conducted analyses unicharacter and bicharacter for all characteristics. In analyses unicharacter, the proportion the variance genetic aditive was responsible for more than 50% the total phenotypic variance and the heritabilities have submitted estimates of medium to high magnitudes the for all characteristcs, being 0.46 for weight at emergence, 0.59 for length abdomen, 0.56 for width of abdomen, 0.80 for body length, 0.62 for spermathecae weight, 0.55 for spermathecae diameter, 0.64 for spermathecae volume and 0.62 for weight of ovaries. Genetic correlations favorable of magnitude between 0.46 to 0.86 were found for the associations between weight at emergence, body length and length and width abdomen. When evaluated the relationship between the emergence weight, body length and width and length abdomen with weight, diameter and volume of spermatheca and ovarian weight, the greater genetic correlation was between the weight at emergence and weight of ovaries of 0.49. Genetic correlation of 0.46 was found for the emergence weight and length of the abdomen, 0.86 for weight at emergence and abdomen width and 0.70 for the emergence weight and body length. That all characteristics evaluated in analysis unicharacter have potential of selection and, genetic correlation the weight at emergence and characteristics of spermathecae and weight of ovaries are determined, in part, the same set of genes, indicating that these associations can be used in breeding programs of bees africanized, for the greater reproductive potential of queen bees A. mellifera africanized .

Fenugreek (Trigonella foenum-graecum L.) was recently introduced to western Canada as a forage crop. To reach its full potential, high yielding, early maturing fenugreek cultivars that produce good seed yield and quality within 100 frost free days need to be developed. In this study, mutation breeding approach was used on five locally adapted fenugreek genotypes to generate variants showing improved seed yield and yield attributing traits that can be used for cultivar development. Mutant generations of these plants were evaluated in multi-location, multi-year trials, and individual plants were selected for high seed and biomass yield. Seeds from a tetraploid fenugreek line and its diploid parent Tristar were grown under multiple environments to understand effect of environment on seed oil content. In addition, mold resistant fenugreek genotypes were identified by screening a collection of fenugreek accessions against a destructive fungal pathogen Cercospora traversiana. / xv, 179 leaves : ill. ; 29 cm

The Kin Selection Hypothesis proposes that the genes associated with male androphilia (i.e., sexual attraction/arousal to adult males) may be maintained over evolutionary time if the fitness costs of not reproducing directly are offset by increasing one’s indirect fitness. Theoretically, this could be accomplished by allocating altruism toward kin which would increase the recipient’s ability to survive and reproduce. Evidence for this hypothesis has been garnered through research conducted in Samoa however, no support has been garnered from research conducted in more industrialized cultures (i.e., USA, UK, Japan). In this thesis, I use a Canadian population to examine: (1) the role geographic proximity plays in the expression of androphilic male avuncularity and (2) whether androphilic males direct altruism toward the children of friends who might represent proxies for nieces and nephews in more industrialized cultures. Other sociocultural factors that potentially influence the expression of androphilic male avuncularity are also discussed. / ix, 81 leaves ; 29 cm