Bibliography: leaves 183-203. / System requirements for accompanying computer disk: IBM compatible computer. Other requirements: Pascal Compiler/Interpreter. / x, 203 leaves : ill. ; 30 cm. + 1 computer disk (3 1/2 in.). / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This study examines how patterns of genetic diversity can be used to gain insights into various aspects of metapopulation dynamics. The first section of this thesis considers the relationship between the rate at which individuals enter a population, and their impact in terms of gene flow, this involved a laboratory experiment using Drosophilia melanogaster. The second section explores the value of using genetic diversity data to make qualitative "rules of thumb" decisions when managing the dynamics of metapopulations. / Thesis (Ph.D.)--Adelaide University, Dept. of Applied and Molecular Ecology, 2001

Thesis (M.Sc. (Med.))--University of the Witwatersrand, Faculty of Health Sciences, 1998. / The issue of Malagasy ancestry has been controversial, and has still not been completely resolved. The historical, linguistic, archaeological and some genetic evidence points to the fact that modern Malagasy are the descendants of immigrants who arrived on the island over the past 2000 years, from South and Southeast Asia, Africa and the Near East. In more recent centuries, mainly in the twentieth century, there have been significant numbers of Indian, Chinese and French immigrants. In addition, archaeological and historical studies of specific regional populations of Malagasy suggest a complex pattern of internal migration within the island, extending back in time to the first European contacts with the island in the sixteenth century. The 22 Malagasy ethnic groups may be classified as "highland" or "lowland" depending on their geographic distribution on the island. Within the ethnic groups, the founding populations have made different genetic contributions: the highland groups are said to have a greater Indonesian contribution to their ancestry, while the lowlanders have a greater African contribution to their ancestry. Genetic studies on the Malagasy have been limited by small sample sizes, deficiencies in sampling procedures and in the limited number of polymorphisms studied. In light of the paucity of written records, the Department of Human Genetics, SAIMR, has undertaken a large study in Madagascar to reconstruct the biological history of its people, using genetic variation. This thesis forms a part of this study. Variation in the a- and p-globin cluster has been extensively studied in many parts of the world, and has been shown to be population specific, with specific variants having distinct geographical distributions. Thus haemoglobin and its related disorders have been the subject of extensive studies for determining the origin(s) of particular populations. In this study, some of the a- and p-globin variation present in the Malagasy was characterised. Seven RFLPs/HVRs in the a-globin gene cluster and seven RFLPs in the p-globin gene cluster were analysed. The common a- and p-globin gene cluster haplotypes differ between African and Asian populations. Frequencies also vary between populations in a specific geographical regions. The aim of this study was to characterise the haplotypes present in the Malagasy, to provide information on the relative genetic contributions of different populations to the peoples of Madagascar. DNA samples from randomly selected, haematologically normal individuals were analysed. Individuals were chosen from six Malagasy ethnic groups: two “highland” populations (Merina and Betsileo), two “lowland" populations (Antasaka and Tsimiheti) and two populations from the south-west of the island (Mahafaly and Vezo). The groups chosen cover a broad range of Madagascar and thus provide some representation of the Malagasy population as a whole. The number of individuals studied in each ethnic group are as follows: Merina: 88; Betsileo: 78; Antasaka: 67; Tsimiheti: 67; Mahafaly: 26; Vezo: 25. The frequencies of the a- and (B-globin RFLP sites and a-globin HVRs in the Malagasy vere calculated. 5' and 3’ p-globin haplotypes were constructed on the basis of homozygosity. A maximum-likelihood algorithm was used to obtain frequencies of 5’ P-globin haplotypes that could not be assigned on the basis of homozygosity. These data were then subject to statistical analysis. The frequencies of the 5’ p-globin haplotypes (consisting of the five sites Hindi 5' to e, Hindi 11 within Gy and Ay, Hindi within \|/P and 3' to it) were the most informative data set for comparing the Malagasy ethnic groups to each other and to other world populations. Unfortunately, the maximum-likelihood estimates of 5‘ p-globin haplotypes could not be used for comparative analyses due to the lack of similar data in other populations. However the strong correlation between the maximum-likelihood frequencies and the observed frequencies illustrated the ability of the algorithm to determine hapiotype frequencies from otherwise uninformative individuals. 5’ p-globin haplotypes were assigned unambiguously for 248 Malagasy chromosomes. Ten haplotypes were found; of these, nine have been reported previously in other world populations and one has not been reported and hns thus been called “rare” in this study. The frequencies of unambiguous 5’ p-globin haplotypes in the Malagasy and the proposed parental populations were initially analysed with x2 tests. For a more accurate comparison between these populations, genetic distances were calculated and used for the construction of phylogenetic trees, principle component analysis was carried out, and a study of heterozygosity versus distance from the centroid was performed. Admixture estimates of two African populations and one Indonesian population to Malagasy ancestry were calculated. Certain general trends were noted in all the analyses. The results are in agreement with the historical data which provides evidence for both African and Asian contributions to Malagasy ancestry. The highlanders were more closely affiliated to the Indonesian/Polynesian populations, while the south-west groups showed the strongest associations with the African populations. The lowlanders were consistently intermediate in position between the highlanders and the south-west groups, with the Antasaka being slightly more closely related to the African populations than the Tsimiheti. The Malagasy were shown to have high heterozygosities, similar to those of African populations, and this high degree of diversity is probably a reflection of the many sources of ancestry of the Malagasy. The south-west groups were the furthest outliers in the model of heterozygosity versus distance from the centroid, suggesting that these groups are the most genetically admixed of all the Malagasy groups that were studied. Estimates of ancestral population admixture confirmed these trends, with the highlanders having the highest proportional contribution by Indonesians (53%), but the lowest total African contribution (47%), while the south-west groups have the highest Bantu contribution (65%). The Indonesian and African contributions to the lowlanders are intermediate between those to highlanders and south-west groups. Overall the Malagasy subjects included in this study showed a 61% African admixture contribution and a 39% Indonesian admixture contribution. It is hoped that the results obtained in this study will contribute to the larger project concerning the origins of the Malagasy, and that they may be used to shed further light on the much debated issue of Malagasy ancestry.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 5 uppsatser.

By definition "adaptability" is the ability of living systems to cope with change. Genetic adaptability requires the production of genetic variation. The view that variation production is undirected or random, i.e. unconnected with selection, implies that selection does not tailor genetic adaptability. But many genetic elements are known to modify processes of variation production, and secondary selection can act on them, so that view is not justified. Over the longer term, natural selection 'favors' properties important, in maintaining immediate fitness, as well as properties important for persistence in the short term. Genetic adaptability is less important in the short term, and is ignored in models based on short term definitions of fitness (e.g. relative effective rate of increase). If "fitness" is to be "the properties favored by natural selection", then its definition should be time scale dependent. Currently prevalent short term definitions of the action of natural selection should not be allowed to hamper consideration of the role of slow processes in determining long term evolutionary patterns. A review of patterns in genome size, and the existing explanations for them, reveals that most explanations are based on notions of adaptedness to the state of the environment. An explanation of genome size patterns based on the rate of change of environments is proposed. It is hypothesized that part of the genome is involved in regulating variation production, and that more DNA means slower production of additive genetic variation. This new hypothesis is simple, general, and testable, but requires more evidence. The question is raised of whether genomes might be organized to facilitate the adjustment of genetic variation production by natural selection. / Science, Faculty of / Zoology, Department of / Graduate

The present study aimed to gain better insights into the distribution of genomic variation, in the form of single nucleotide polymorphisms, within the human genome.  Using set theory, the average SNP density of the human genome was found to be 2.6 SNPs per kilobase.  This figure decreased with increasing evolutionary depth, i.e. conservation.  The conserved exonic, intronic subsets had a lower SNP density than the conserved intergenic subset, suggesting that the conserved exonic and intronic regions are under similar strengths of selective pressure while conserved intergenic regions are under a comparatively weaker selective pressure.  To better understand allelic differences on protein-DNA interactions, an algorithm was designed that scored the difference in binding site prediction for the alleles of an SNP.  The program created, RegSNP, was demonstrated to be more accurate than existing resources, and gives results that are relevant of SNP within binding sites in the literature. A further aim of the present study was to isolate potential regulatory regions of the GAL gene, that has been linked to diseases such as obesity and depression, and identify polymorphisms that may alter transcription factor binding.  One excellent candidate element was found by comparative genomics, Gal5.1, and confirmed by transgenic analysis as a transcriptional enhancer element.  Gal5.1, contained a single SNP that RegSNP predicted to interrupt a thyroid hormone receptor binding site.  However, using transgenic animal and cell biology techniques it was concluded that thyroid hormone receptor does not directly interact with the Gal5.1 element, suggesting that the Gal5.1 element must work in synergy with the GAL promoter to stimulate transcription.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.