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Developmental Gene Expression Differences between Humans and Mammalian Models.

Margarida Cardoso-Moreira1, Ioannis Sarropoulos1, Britta Velten2

  • 1Center for Molecular Biology (ZMBH), DKFZ-ZMBH Alliance, Heidelberg University, 69120 Heidelberg, Germany.

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|October 28, 2020
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Summary
This summary is machine-generated.

Human organ development involves complex gene expression patterns. Comparing these patterns across species reveals significant differences, particularly for genes linked to brain, heart, and liver diseases, questioning the reliability of mouse models.

Keywords:
animal modelscomparative transcriptomicsdevelopmentgene expressionhuman diseaseorganogenesis

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Area of Science:

  • Developmental biology
  • Comparative genomics
  • Human genetics

Background:

  • Understanding human organ development is crucial for health and disease research.
  • Gene expression profiles offer insights into developmental processes and cross-species comparisons.
  • Differences in developmental gene expression between humans and model organisms can impact disease modeling.

Purpose of the Study:

  • To characterize temporal gene expression profiles in seven human organs during development.
  • To associate these profiles with distinct disease classes.
  • To compare human gene spatiotemporal expression with orthologs in non-human primates and rodents.

Main Methods:

  • Utilized a transcriptomic resource for seven developing human organs.
  • Analyzed temporal gene expression profiles of human disease-associated genes.
  • Quantified spatiotemporal expression similarity between human genes and their orthologs in rhesus macaque, mouse, rat, and rabbit.

Main Results:

  • Established clear associations between gene spatiotemporal profiles and disease phenotypes.
  • Found that approximately half of human genes exhibit divergent temporal expression trajectories compared to their mouse orthologs in at least one organ.
  • Identified over 200 genes linked to brain, heart, and liver diseases with significant cross-species expression differences.

Conclusions:

  • Human organ development gene expression patterns are linked to disease manifestations.
  • Significant divergence exists in temporal gene expression between humans and mouse orthologs, impacting translational research.
  • Mouse models require careful evaluation for over 200 disease-associated genes due to cross-species expression differences.