Differential DNA Preservation of Thermally Altered Tissue and Bone
- Author (aut): Coffman, Amber
- Thesis advisor (ths): Stone, Anne C
- Committee member: Parker, Cody
- Committee member: Kanthaswamy, Sreetharan
- Publisher (pbl): Arizona State University
The study of macaque monkeys harbors advancements in the field of biomedical research. It is imperative to understand the genetic composition of different species of macaques to assess their accuracy as non-human primate (NHP) models for disease detection and treatment assessments. We sought to characterize the hybridization and admixture of the Southeast Asian macaques using single nucleotide polymorphism markers and analyzing the populations on the mainland and the island. Using AMOVA tests and STRUCTURE analysis, we determined that there are three distinct populations: Macaca mulatta, M. fascicularis fascicularis, and M. f. aurea. Furthermore, the island species holds an isolated population of M. f. aurea that demonstrate high inbreeding and genetic uniqueness compared to the mainland species. Findings from this study confirm that NHP models may need to be modified or updated according to changing allelic frequencies and genetic drift.
We used the Affymetrix® Genome-Wide Human SNP Array 6.0 to identify heterospecific markers and compare copy number and structural genomic variation between humans and rhesus macaques. Over 200,000 human copy number variation (CNV) probes were mapped to a Chinese and an Indian rhesus macaque sample. Observed genomic rearrangements and synteny were in agreement with the results of a previously published genomic comparison between humans and rhesus macaques. Comparisons between each of the two rhesus macaques and humans yielded 206 regions with copy numbers that differed by at least two fold in the Indian rhesus macaque and human, 32 in the Chinese rhesus macaque and human, and 147 in both rhesus macaques. The detailed genomic map and preliminary CNV data are useful for better understanding genetic variation in rhesus macaques, identifying derived changes in human CNVs that may have evolved by selection, and determining the suitability of rhesus macaques as human models for particular biomedical studies.
Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole genome sequencing analysis of 133 rhesus macaques revealed >43.7 million single nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and non-coding variation, and its cellular consequences. Despite modestly higher levels of non-synonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of non-synonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease.