Related Experiment Video
Updated: May 5, 2026
Single Cell Transcriptional Profiling of Adult Mouse Cardiomyocytes
Published on: December 28, 2011
Transcriptomic and genetic profiling in a spontaneous non-human primate model of hypertrophic cardiomyopathy and
Victor N Rivas1,2, Michael W Vandewege1, Yu Ueda1
1Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dr, Raleigh, NC, 27607, USA.
Insights
Genetic analysis in rhesus macaques did not identify specific variants causing hypertrophic cardiomyopathy (HCM). Transcriptomic data revealed altered gene expression, particularly MAFF, and channelopathy links, but no clear genetic cause for HCM was found.
Area of Science:
- Cardiovascular Genetics
- Primate Models
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a significant cardiac disease affecting multiple species, including rhesus macaques.
- While sarcomeric mutations are implicated in human and feline HCM, the genetic underpinnings in rhesus macaques remain elusive.
- Understanding the molecular basis of HCM in rhesus macaques is crucial for comparative pathology and disease modeling.
Purpose of the Study:
- To investigate the transcriptomic and genomic basis of hypertrophic cardiomyopathy (HCM) in rhesus macaques.
- To identify potential genetic variants or molecular pathways associated with HCM development and sudden cardiac death (SCD) in this primate model.
- To establish a valuable, open-access dataset for future cardiovascular disease research.
Main Methods:
- RNA-sequencing (RNA-Seq) of left ventricular (LV) tissues from HCM-affected and control rhesus macaques for differential gene expression analysis.
- Whole-genome sequencing (WGS) of HCM-affected and healthy geriatric rhesus macaques.
- Genome-wide association study (GWAS) and polygenic modeling to identify disease-associated genetic variants.
Main Results:
- Differential gene expression analysis identified 614 downregulated and 1,065 upregulated genes, with MAFF being significantly overexpressed in affected animals.
- Transcriptomic data suggested channelopathy-associated pathways in approximately 57% of downregulated differentially expressed genes, indicating hypertrophic and arrhythmic processes.
- Genome-wide association studies and polygenic modeling failed to identify significant genetic variants or profiles associated with HCM or SCD in the studied rhesus macaque population.
Conclusions:
- The study did not uncover specific single or compound genetic variants, nor a polygenic profile, that explain hypertrophic cardiomyopathy (HCM) in rhesus macaques.
- Transcriptomic findings point towards channelopathy and altered gene expression as potential contributors, but a clear genetic etiology remains unidentified.
- The generated dataset of phenotyped rhesus macaques provides a valuable resource for future research into the genetic basis of cardiovascular diseases in non-human primates.
Abstract:
Hypertrophic cardiomyopathy (HCM) afflicts humans, cats, pigs, and rhesus macaques. Disease sequelae include congestive heart failure, thromboembolism, and sudden cardiac death (SCD). Sarcomeric mutations explain some human and cat cases, however, the molecular basis in rhesus macaques remains unknown. RNA-Seq of the LV tissues of five HCM-affected and seven healthy control rhesus macaques was employed for differential transcriptomic analyses. DNA from 15 severely HCM-affected and 21 healthy geriatric rhesus macaques were selected for whole-genome sequencing. A genome-wide association study (GWAS) of disease status and SCD outcome was performed. 614 down- and 1,065 upregulated differentially expressed genes (DEGs) were identified between groups. The top DEG (MAFF) was overexpressed in affected animals (log2FoldChange = 4.71; PAdjusted-value = 1.14E-133). Channelopathy-associated enriched terms were identified in ~ 57% of downregulated DEGs providing transcriptomic evidence of hypertrophic and arrhythmic disease processes. For GWAS, no putative variant withstood segregation. Polygenic modeling analysis resulted in poor prediction power and burden testing could not explain HCM by an association of multiple variants in any gene. Neither single nor compound genetic variant(s), or identified polygenic profile, suggest complex genotype-phenotype interactions in rhesus macaques. Brought forth is an established dataset of robustly phenotyped rhesus macaques as an open-access resource for future cardiovascular disease genetic studies.
More Related Videos
09:29Assessing Cardiomyocyte Subtypes Following Transcription Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts
Published on: March 22, 2017
03:45Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
