Evaluation of Five Mammalian Models for Human Disease Research Using Genomic and Bioinformatic Approaches

Abstract

The suitability of an animal model for use in studying human diseases relies heavily on the similarities between the two species at the genetic, epigenetic, and metabolic levels. However, there is a lack of consistent data from different animal models at each level to evaluate this suitability. With the availability of genome sequences for many mammalian species, it is now possible to compare animal models based on genomic similarities. Herein, we compare the coding sequences (CDSs) of five mammalian models, including rhesus macaque, marmoset, pig, mouse, and rat models, with human coding sequences. We identified 10,316 conserved CDSs across the five organisms and the human genome based on sequence similarity. Mapping the human-disease-associated single-nucleotide polymorphisms (SNPs) from these conserved CDSs in each species has identified species-specific associations with various human diseases. While associations with a disease such as colon cancer were prevalent in multiple model species, the rhesus macaque showed the most model-specific human disease associations. Based on the percentage of disease-associated SNP-containing genes, marmoset models are well suited to study many human ailments, including behavioral and cardiovascular diseases. This study demonstrates a genomic similarity evaluation of five animal models against human CDSs that could help investigators select a suitable animal model for studying their target disease.