Human Molecular Genetics Advance Access published online on December 12, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl456
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© The Author 2006. Published by Oxford University Press. All rights reserved
Replicated Effects of Sex and Genotype on Gene Expression in Human Lymphoblastoid Cell Lines
1 Genetic Epidemiology Group, Queensland Institute of Medical Research, Herston, QLD, 4029, Australia 2 Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD, 4076, Australia 3 Human Genetics Laboratory, Queensland Institute of Medical Research, Herston, QLD, 4029, Australia 4 Epilepsy Research Centre, Department of Medicine (Neurology), University of Melbourne, Austin Health, Heidelberg, Victoria, Australia 5 Academic Unit of Medicine (Neurology), The Australian National University, Canberra, Australia 6 Department of Genetic Medicine, Women's and Children's Hospital, North Adelaide, Australia 7 Department of Molecular Biosciences, University of Adelaide, Adelaide, South Australia, Australia 8 Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, EH9 3JT, United Kingdom
Corresponding Author: Allan F McRae Email: allan.mcrae{at}qimr.edu.au Phone: +61 7 3362 0190 Fax: +61 7 3362 0101
Received September 26, 2006; Revised November 14, 2006; Accepted November 28, 2006
The expression level for 15887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On average the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences.
* These authors contributed equally