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

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Authors
Kim, Yoonhee; Doan, Betty Q; Duggal, Priya; Bailey-Wilson, Joan E
Issue Date
2007-12-18
Publisher
BioMed Central
Citation
BMC Proceedings, 1(Suppl 1):S152
Abstract
"Genetical genomics", the study of natural genetic variation combining data from genetic marker-based studies with gene expression analyses, has exploded with the recent development of advanced microarray technologies. To account for systematic variation known to exist in microarray data, it is critical to properly normalize gene expression traits before performing genetic linkage analyses. However, imposing equal means and variances across pedigrees can over-correct for the true biological variation by ignoring familial correlations in expression values. We applied the robust multiarray average (RMA) method to gene expression trait data from 14 Centre d'Etude du Polymorphisme Humain (CEPH) Utah pedigrees provided by GAW15 (Genetic Analysis Workshop 15). We compared the RMA normalization method using within-pedigree pools to RMA normalization using all individuals in a single pool, which ignores pedigree membership, and investigated the effects of these different methods on 18 gene expression traits previously found to be linked to regions containing the corresponding structural locus. Familial correlation coefficients of the expressed traits were stronger when traits were normalized within pedigrees. Surprisingly, the linkage plots for these traits were similar, suggesting that although heritability increases when traits are normalized within pedigrees, the strength of linkage evidence does not necessarily change substantially.
Language
English
URI
http://hdl.handle.net/10371/109989
DOI
https://doi.org/10.1186/1753-6561-1-S1-S152
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Graduate School of Public Health (보건대학원)Dept. of Public Health (보건학과)Journal Papers (저널논문_보건학과)
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