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Related Experiment Videos

Normalization of microarray expression data using within-pedigree pool and its effect on linkage analysis.

Yoonhee Kim1, Betty Q Doan, Priya Duggal

  • 1Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, 333 Cassell Drive, Suite 1200, Baltimore, Maryland 21224, USA. nina78@snu.ac.kr

BMC Proceedings
|May 10, 2008
PubMed
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Normalizing gene expression data within pedigrees strengthens familial correlations but does not significantly alter genetic linkage evidence. This study explores robust multiarray average (RMA) normalization for genetical genomics research.

Area of Science:

  • Genetical genomics
  • Systems biology
  • Statistical genetics

Background:

  • Genetical genomics integrates genetic variation studies with gene expression analysis using microarray data.
  • Accurate normalization of gene expression is crucial for genetic linkage analysis.
  • Standard normalization may over-correct by ignoring familial correlations in expression.

Purpose of the Study:

  • To compare Robust Multiarray Average (RMA) normalization methods for gene expression data in familial studies.
  • To investigate the impact of within-pedigree versus single-pool normalization on genetic linkage analysis.
  • To assess the effect of normalization strategies on familial correlation and linkage evidence.

Main Methods:

  • Applied the RMA normalization method to gene expression data from 14 CEPH Utah pedigrees (GAW15).

Related Experiment Videos

  • Compared within-pedigree RMA pooling against single-pool RMA normalization (ignoring pedigree structure).
  • Analyzed 18 gene expression traits previously linked to specific genomic regions.

    • Main Results:

    • Familial correlation coefficients were higher for traits normalized within pedigrees.
    • Linkage plots showed similar results despite increased heritability from within-pedigree normalization.
    • Normalization strategy impacts familial correlation but not necessarily the strength of linkage evidence.

    Conclusions:

    • Within-pedigree normalization enhances the detection of familial correlations in gene expression.
    • Robust multiarray average (RMA) normalization strategies yield comparable genetic linkage results.
    • Careful consideration of normalization is important in genetical genomics to balance biological variation and statistical analysis.