Doctor of Philosophy

dissertationAnthropologists provide a valuable service to the medico-legal community. They are tasked with creating a biological profile and helping with the ultimate identification of unknown remains. This can often be a difficult task when the anthropologists require something to which they can compare the biological profile and create a small group of potential matches. This endeavor can be greatly enhanced by access to medical patient databases and identification techniques which are able to utilize specific disease databases in conjunction with the biological profile. The research presented here explores the genetic connection between the eye disease Age-Related Macular Degeneration (AMD), and the bone disease Ossification of the Posterior Longitudinal Ligament (OPLL) as a new avenue of identification. The research conducted looked at the specific genetic marker that connects the two diseases, the interaction of this genetic risk factor with other risk genes in AMD, and the prevalence and presentation of OPLL in non-Asian populations. The results of the project provided a great deal of insight into a possible therapeutic target for AMD and suggests that the previously reported statistics on OPLL both in, and out, of Asia are grossly underestimated, thus the disease should be reexamined in all populations throughout the world. In addition, the results and parameters of this research advocate future research into an identification method based on the genetic connection between these two diseases

Comparative genomic and phylogenetic approaches to characterize the role of genetic recombination in mycobacterial evolution

The genus Mycobacterium encompasses over one hundred named species of environmental and pathogenic organisms, including the causative agents of devastating human diseases such as tuberculosis and leprosy. The success of these human pathogens is due in part to their ability to rapidly adapt to their changing environment and host. Recombination is the fastest way for bacterial genomes to acquire genetic material, but conflicting results about the extent of recombination in the genus Mycobacterium have been reported. We examined a data set comprising 18 distinct strains from 13 named species for evidence of recombination. Genomic regions common to all strains (accounting for 10% to 22% of the full genomes of all examined species) were aligned and concatenated in the chromosomal order of one mycobacterial reference species. The concatenated sequence was screened for evidence of recombination using a variety of statistical methods, with each proposed event evaluated by comparing maximum-likelihood phylogenies of the recombinant section with the non-recombinant portion of the dataset. Incongruent phylogenies were identified by comparing the site-wise log-likelihoods of each tree using multiple tests. We also used a phylogenomic approach to identify genes that may have been acquired through horizontal transfer from non-mycobacterial sources. The most frequent associated lineages (and potential gene transfer partners) in the Mycobacterium lineage-restricted gene trees are other members of suborder Corynebacterinae, but more-distant partners were identified as well. In two examined cases of potentially frequent and habitat-directed transfer ( M. abscessus to Segniliparus and M. smegmatis to Streptomyces ), observed sequence distances were small and consistent with a hypothesis of transfer, while in a third case ( M. vanbaalenii to Streptomyces ) distances were larger. The analyses described here indicate that whereas evidence of recombination in core regions within the genus is relatively sparse, the acquisition of genes from non-mycobacterial lineages is a significant feature of mycobacterial evolution

Recovery of cohesive mycobacterial clans.

<p>The number of trees for proteins in Groups II, III and IV from each mycobacterial genome that recovered genus <i>Mycobacterium</i> as a clan (dark grey) or as multiple groups interspersed with proteins from other genera (light grey) is shown.</p

Percentage of protein sets from each mycobacterial strain assigned to Groups I-IV.

<p>Strains are grouped according to the four main divisions identified in the text.</p