Exon and junction microarrays detect widespread mouse strain- and sex-bias expression differences

Area of Science:

• Genomics
• Transcriptomics
• Molecular Biology

Background:

• Genetic and sex differences are known to influence gene expression in mice.
• Alternative splicing generates transcript diversity, necessitating comprehensive expression analysis.

Purpose of the Study:

• To investigate the impact of mouse strain and sex on liver gene and exon expression.
• To compare the effectiveness of different microarray profiling methods in detecting expression variations.

Main Methods:

• Utilized a custom microarray to profile exon and exon-junction expression in 71 liver RNA samples from three inbred mouse strains (DBA/2J, C57BL/6J, C3H/HeJ).
• Employed three expression profiling methods: 3' gene expression, whole-transcript gene expression, and exon expression profiling.
• Analyzed data using two-way Analysis of Variance (ANOVA) to detect strain and sex influences.

Main Results:

• Widespread strain and sex influences on gene and exon expression were detected across all profiling methods.
• Exon expression profiling identified over 90% of genes found by other methods, plus additional genes with differential isoform expression.
• Significant strain- (55%) and sex-biased (32%) differential gene or exon expression was observed.

Conclusions:

• Exon expression profiling is superior for detecting expression variation compared to 3' and whole-transcript methods.
• A substantial proportion of genes show exon-level variation without differential gene-level expression, indicating strain and sex effects on alternative splicing.
• Profiling at sub-gene resolution is crucial for understanding complex expression changes influenced by genetic background and sex.