The present thesis covers two aspects of statistical analysis applied to the genetics of human diseases. First, the significance of LOD-score results for the confirmation of linkage is addressed, with special emphasis on small pedigrees. A new analytical approach is presented for the linkage analysis of heterogenetic traits, using hereditary spastic paraplegia as a model, a disease well suited for the analyses. The critical significance values for confirmation of linkage are evaluated using Bayesian statistics, and empirical P-values for LOD score results are calculated using computer simulation methods. The presented analytical approach resulted in conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity. / The second part addresses linkage-disequilibrium based fine mapping in the French Canadian population. The performance of five linkage-disequilibrium based fine-mapping methods is evaluated using French Canadian chromosomes with one of three diseases found in this population: oculopharyngeal muscular dystrophy (OPMD), hidrotic ectodermal dysplasia (HED), and sensorimotor polyneuropathy with or without agenesis of the corpus callosum (ACCPN). The gene for OPMD was recently mapped and cloned, allowing us to evaluate the performance of the methods with the OPMD results, and to make predictions about the ACCPN and HED putative gene positions. In addition, a new approach to linkage-disequilibrium based fine mapping is presented using FrenchCanadian ascending genealogies. The method involves two steps. First, the likely founding couple of a mutation-bearing chromosome is identified using a computerised randomisation statistic. Then, using a delete-d jackknife resampling scheme, the distribution of gene mapping estimates is calculated from the count of ancestral recombinants and ancestral meioses joining the identified founding couple to the disease gene carriers. Gene mapping estimates are calculated from each marker individually, and confidence intervals of the estimates are derived from the jackknife distributions. The method, when applied to French Canadian families with OPMD, successfully confirmed the localisation of PABP2 responsible for OPMD and performed better than other linkage disequilibrium-based mapping models.

Thesis (Ph. D.)--University of Tartu, 2004. / Includes reprint of 5 previously published articles. Includes bibliographical references.

No description available.

No description available.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 120-144).

No description available.

The purpose of this research endeavor was to determine the extent of genetic relatedness between an ancient and modern Miami Indian population. The modern Miami Indian nation in Indiana is currently in the process of regaining the federal recognition which was lost in the mid 1800's when part of the tribe was forced to relocate. A close genetic relationship between a modern and known ancient population could considerably strengthen the case to regain federal recognition. The human skeletal remains used for this experiment were excavated after partial exposure by flooding between 1989-1993 along the banks of the Mississinewa River in Wabash County. Through ethnohistoric dating techniques, the remains have been shown to represent a Miami Indian population living between 1790-1820. In order to yield amplifiable DNA several methods of isolation were attempted and compared. CTAB and phenol/chloroform/isoamyl alcohol (24:24:1) and a silica based purification method provided the best results yielding approximately 50-100 ng of amplifiable DNA from 3 of the 4 individuals. Purification of the DNA was found to be necessary following both isolation (Elu-Quik) prior to PCR amplification and after PCR but prior to sub-cloning(Gene-Clean). Regions of the mitochondrial DNA (mtDNA) genome of isolated DNA were amplified using primers which are specific for the HIizcIl and AIui regions of the mtDNA genome. Although the mtDNA proved to be somewhat amplifiable, it was still too fragmented to be cloned, which prevented genetic analysis and comparison of the two populations. As a result, a discussion of alternative methods for looking at relatedness between populations has been included. / Department of Biology

Thesis (Ph. D.)--University of Canterbury, 2007. / Typescript (photocopy). Includes bibliographical references (p. 121-135). Also available via the World Wide Web.

Thesis (M.A.)--State University of New York at Binghamton, Department of Anthropology, 2009. / Includes bibliographical reference (leaves: 181-197).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.