Dr. Spradling-Reeves recently oversaw the development and optimization of a new high-throughput, multiplexed genotype-by-sequencing (GbS) protocol for nonhuman primates (NHP). Her group is currently using this method to identify single nucleotide variation associated with hypertension in a panel of 770 baboons. GbS will also be used to genotype other NHP species in the Southwest National Primate Research Center colony at Texas Biomed.
Obesity has become a major global epidemic that affects people of all ages, demonstrating the critical need to enhance our understanding of the causes of obesity and obesity-related diseases.
She conducts her studies as part of the research group led by Dr. Laura Cox.
Baboon kidney transcriptomeThe baboon is closely related to humans and a popular laboratory primate species, suitable for the genetic study of complex traits and susceptibility to complex diseases. To enhance the baboon as a model for biomedical research, we used high-throughput RNA-Seq to examine the baboon kidney transcriptome. We successfully identified 45,499 high-confidence SNPs, 29,813 InDels, and 35,900 cDNAs in the baboon kidney, including 35,150 transcripts representing 15,369 genic genes that are novel for the baboon. Since about 75% of protein-coding genes are ubiquitously expressed across all tissues and cell lines, most identified kidney transcripts are presumably ubiquitously expressed, providing insight into the core transcriptome of the baboon. This presents a new transcriptome resource using the baboon as an experimental model.
The gut microbiome is assumed to influence obesity development by interacting with the host physiology. Early studies indicate that the ratio of two bacterial phyla (Bacteroidetes and Firmicutes) marks the difference between the lean and obese phenotype, but causative microorganisms are unknown. Using a “proteo-genomics” approach, we explore the baboon gut microbiome at multiple molecular levels. Metagenomic sequence data identifies microbial species and their metabolic potential, while metaproteomic data provides information on the abundance of expressed proteins in baboons fed an obesity-inducing high-fat, high-sugar diet. Integrated datasets reveal affected genes, proteins, and pathways to identify potential therapeutic targets.
Systems biology analysis of gut microbiota in the baboon model of obesity
Gene variants and mechanisms underlying salt-sensitive hypertension
About 28% of US adults suffer from treatment-resistant hypertension. Since specific genetic variants are regulating blood pressure, medications are often ineffective. To study gene variants and molecular mechanisms that influence the risk of salt-sensitive hypertension, we performed whole transcriptome profiling (RNA-Seq, small RNA-Seq) on baboons (kidney biopsy samples) discordant for hypertension and the hypertension phenotype sodium-lithium countertransport (SLC), following two diets differing in sodium content. Gene expression data analysis showed sodium-responsive transcripts with a discordant expression between normal and high blood pressure baboons. Our high-throughput, multiplexed GbS protocol identified single-nucleotide variants in candidate genes and miRNAs associated with SLC variation in 770 baboons. Bayesian quantitative trait nucleotide analysis will identify polymorphisms that influence blood pressure, to provide biomarkers and therapeutic targets.
- Nucleic acid extractions from a variety of tissue sources
- Gene expression profiling
- Genotype-by-sequencing (GbS)
- Analysis of gene array, RNA-Seq, small RNA-Seq, and DNA-Seq datasets using Partek Flow® and Genomics Suite, GeneSifter, and Ingenuity Pathways Analysis software
- Analysis of metagenomic data