Jagadesan, S.; Mondal, P.; Carlson, M.A.; Guda, C. Evaluation of Five Mammalian Models for Human Disease Research Using Genomic and Bioinformatic Approaches. Biomedicines2023, 11, 2197.
Jagadesan, S.; Mondal, P.; Carlson, M.A.; Guda, C. Evaluation of Five Mammalian Models for Human Disease Research Using Genomic and Bioinformatic Approaches. Biomedicines 2023, 11, 2197.
Jagadesan, S.; Mondal, P.; Carlson, M.A.; Guda, C. Evaluation of Five Mammalian Models for Human Disease Research Using Genomic and Bioinformatic Approaches. Biomedicines2023, 11, 2197.
Jagadesan, S.; Mondal, P.; Carlson, M.A.; Guda, C. Evaluation of Five Mammalian Models for Human Disease Research Using Genomic and Bioinformatic Approaches. Biomedicines 2023, 11, 2197.
Abstract
The suitability of an animal model to study human diseases heavily relies on the similarity between the two species at the genetic, epigenetic, gene expression and metabolic levels. However, consistent data from different animal models at each level to evaluate this suitability is lacking. With the availability of genome sequences for many mammalian species it is now possible to compare animal models based on the genomic similarities. Here, we compare the coding sequences (CDS) of five mammalian models that include rhesus macaque, marmoset, pig, mouse and rat with those from human. We identified 10,316 conserved CDS across the five organisms and human based on the sequence similarity. Mapping the human disease-associated single nucleotide polymorphisms (SNPs) from these conserved CDS in each species has identified species-specific association with various human diseases. While associations for a disease such as colon cancer were prevalent in multiple model species, pig showed the highest number (117 diseases) of 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 gastrointestinal diseases. Comparison of gene expression levels of the conserved CDS from colon, heart, kidney, lung, skeletal muscle, and spleen tissues in these models showed correlations with human expression levels in a tissue-specific manner. In the gastrointestinal tissues (colon, spleen), the pig showed the highest correlation while mouse displayed a better correlation in the heart and kidney. This study demonstrated genomic as well as tissue-specific expression-based similarity evaluation of five animal models against human that could help investigators select a suitable animal model to study their targeted disease.
Keywords
Animal models; NHPs; rodents; marmoset; sequence similarity; SNPs; human diseases
Subject
Biology and Life Sciences, Animal Science, Veterinary Science and Zoology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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