Population genetics of VNTR loci and their applications in evolutionary studies

Variable number of tandem repeats (VNTR) are genetic loci at which short sequence motifs are found repeated different numbers of times among chromosomes. To explore the potential utility of VNTR loci in evolutionary studies, I have conducted a series of studies to address the following questions: (1) What are the population genetic properties of these loci? (2) What are the mutational mechanisms of repeat number change at these loci? (3) Can DNA profiles be used to measure the relatedness between a pair of individuals? (4) Can DNA fingerprint be used to measure the relatedness between populations in evolutionary studies? (5) Can microsatellite and short tandem repeat (STR) loci which mutate stepwisely be used in evolutionary analyses?^ A large number of VNTR loci typed in many populations were studied by means of statistical methods developed recently. The results of this work indicate that there is no significant departure from Hardy-Weinberg expectation (HWE) at VNTR loci in most of the human populations examined, and the departure from HWE in some VNTR loci are not solely caused by the presence of population sub-structure.^ A statistical procedure is developed to investigate the mutational mechanisms of VNTR loci by studying the allele frequency distributions of these loci. Comparisons of frequency distribution data on several hundreds VNTR loci with the predictions of two mutation models demonstrated that there are differences among VNTR loci grouped by repeat unit sizes.^ By extending the ITO method, I derived the distribution of the number of shared bands between individuals with any kinship relationship. A maximum likelihood estimation procedure is proposed to estimate the relatedness between individuals from the observed number of shared bands between them.^ It was believed that classical measures of genetic distance are not applicable to analysis of DNA fingerprints which reveal many minisatellite loci simultaneously in the genome, because the information regarding underlying alleles and loci is not available. I proposed a new measure of genetic distance based on band sharing between individuals that is applicable to DNA fingerprint data.^ To address the concern that microsatellite and STR loci may not be useful for evolutionary studies because of the convergent nature of their mutation mechanisms, by a theoretical study as well as by computer simulation, I conclude that the possible bias caused by the convergent mutations can be corrected, and a novel measure of genetic distance that makes the correction is suggested. In summary, I conclude that hypervariable VNTR loci are useful in evolutionary studies of closely related populations or species, especially in the study of human evolution and the history of geographic dispersal of Homo sapiens. (Abstract shortened by UMI.) ^

Mixture modeling for joint analysis of survival, discrete, and continuous data

Mixture modeling is commonly used to model categorical latent variables that represent subpopulations in which population membership is unknown but can be inferred from the data. In relatively recent years, the potential of finite mixture models has been applied in time-to-event data. However, the commonly used survival mixture model assumes that the effects of the covariates involved in failure times differ across latent classes, but the covariate distribution is homogeneous. The aim of this dissertation is to develop a method to examine time-to-event data in the presence of unobserved heterogeneity under a framework of mixture modeling. A joint model is developed to incorporate the latent survival trajectory along with the observed information for the joint analysis of a time-to-event variable, its discrete and continuous covariates, and a latent class variable. It is assumed that the effects of covariates on survival times and the distribution of covariates vary across different latent classes. The unobservable survival trajectories are identified through estimating the probability that a subject belongs to a particular class based on observed information. We applied this method to a Hodgkin lymphoma study with long-term follow-up and observed four distinct latent classes in terms of long-term survival and distributions of prognostic factors. Our results from simulation studies and from the Hodgkin lymphoma study demonstrated the superiority of our joint model compared with the conventional survival model. This flexible inference method provides more accurate estimation and accommodates unobservable heterogeneity among individuals while taking involved interactions between covariates into consideration.^

Report on the practice based culminating experience as teaching assistant for "Pathology and Public Health" class taught at University of Texas School of Public Health, Houston

Objectives. The objectives of this report were to describe current best standards in online education, class competencies, class objectives, class activities and to compare the class competencies, objectives and activities undertaken with the current best practices in online teaching and to provide a list of recommendations based on the most efficacious practices. ^ Methods. Utilizing the key words- online teaching, national standards, quality, online courses, I: (1) conducted a search on Google to find the best standard for quality online courses; the search yielded National Standards for Quality Online Teaching as the gold standard in online course quality; (2) specified class objectives and competencies as well as major activities undertaken as a part of the class. Utilizing the Southern Regional Education Board evaluation checklist for online courses, I: (1) performed an analysis comparing the class activities, objectives, and competencies with the current best standards; (2) utilized the information obtained from the analysis and class experiences to develop recommendations for the most efficacious online teaching practices. ^ Results. The class met the criteria set by the Southern Regional Education Board for evaluating online classes completely in 75%, partially in 16% and did not meet the criteria in 9% cases. The majority of the parameters in which the class did not meet the standards (4 of 5) were due to technological reasons beyond the scope of the class instructor, teaching assistant and instructional design. ^ Discussion. Successful online teaching requires awareness of technology, good communication, methods, collaboration, reflection and flexibility. Creation of an online community, engaging online learners and utilizing different learning styles and assessment methods promote learning. My report proposes that online teaching should actively engage the students and teachers with multiple interactive strategies as evidenced from current best standards of online education and my “hands-on” work experience. ^ Conclusion. The report and the ideas presented are intended to create a foundation for efficacious practice on the online teaching platform. By following many of the efficacious online practices described in the report and adding from their own experiences, online instructors and teaching assistants can contribute to effective online learning. ^

A practice-based culminating experience: Writing a HRSA grant application with Texas Organ Sharing Alliance for public education efforts to increase solid organ donation

In November 2010, nearly 110,000 people in the United States were waiting for organs for transplantation. Despite the fact that the organ donor registration rate has doubled in the last year, Texas has the lowest registration rate in the nation. Due to the need for improved registration rates in Texas, this practice-based culminating experience was to write an application for federal funding for the central Texas organ procurement organization, Texas Organ Sharing Alliance. The culminating experience has two levels of significance for public health – (1) to engage in an activity to promote organ donation registration, and (2) to provide professional experience in grant writing. ^ The process began with a literature review. The review was to identify successful intervention activities in motivating organ donation registration that could be used in intervention design for the grant application. Conclusions derived from the literature review included (1) the need to specifically encourage family discussions, (2) religious and community leaders can be leveraged to facilitate organ donation conversations in families, (3) communication content must be culturally sensitive and (4) ethnic disparities in transplantation must be acknowledged and discussed.^ Post the literature review; the experience followed a five step process of developing the grant application. The steps included securing permission to proceed, assembling a project team, creation of a project plan and timeline, writing each element of the grant application including the design of proposed intervention activities, and completion of the federal grant application. ^ After the grant application was written, an evaluation of the grant writing process was conducted. Opportunities for improvement were identified. The first opportunity was the need for better timeline management to allow for review of the application by an independent party, iterative development of the budget proposal, and development of collaborative partnerships. Another improvement opportunity was the management of conflict regarding the design of the intervention that stemmed from marketing versus evidence-based approaches. The most important improvement opportunity was the need to develop a more exhaustive evaluation plan.^ Eight supplementary files are attached to appendices: Feasibility Discussion in Appendix 1, Grant Guidance and Workshop Notes in Appendix 2, Presentation to Texas Organ Sharing Alliance in Appendix 3, Team Recruitment Presentation in Appendix 5, Grant Project Narrative in Appendix 7, Federal Application Form in Appendix 8, and Budget Workbook with Budget Narrative in Appendix 9.^