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Stochastic variation of transcript abundance in C57BL/6J mice
Peter T Vedell1, Karen L Svenson, Gary A Churchill
1The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
BMC Genomics
|April 1, 2011
Summary
Gene expression varies significantly between genetically identical mice and within their tissues. This transcript variation highlights the impact of stochastic and environmental factors on biological outcomes.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Transcripts show considerable variation in tissues from inbred laboratory mice.
- Microarray experiments are used to study transcript variation and partition it into within-mouse and between-mouse components.
- Within-mouse variance includes heterogeneity in gene expression, RNA extraction, and array processing, while between-mouse variance reflects differences between genetically identical mice.
Purpose of the Study:
- To examine transcript variation across different tissues (adipose, heart, kidney, liver) in C57BL/6J mice.
- To differentiate between within-mouse and between-mouse sources of transcript variation.
- To understand the biological implications of observed gene expression variability.
Main Methods:
- Microarray experiment design and execution.
- Analysis of transcript variation across multiple tissues.
- Partitioning of variance into within-mouse and between-mouse components.
- Functional enrichment analysis of genes with high variability.
Main Results:
- Transcript variation differs significantly across tissues; adipose exhibits the highest total and within-mouse variance, while liver shows the least total but most between-mouse variance.
- Highly variable genes cluster into groups with correlated expression patterns, enriched for specific biological functions.
- Between-mouse variation is linked to circadian rhythm, immune response, and lipid metabolism, among other functions.
- Within-mouse variation correlates with biological functions reflecting tissue cell-type heterogeneity.
Conclusions:
- Genetically identical mice can exhibit divergent phenotypic outcomes due to variations in gene expression.
- Understanding between-mouse gene expression variability is crucial for experimental design and interpreting data in interventional studies.
- Stochastic and micro-environmental factors significantly influence transcript levels, underscoring their importance in biological variability.
