Human Molecular Genetics Advance Access originally published online on December 12, 2006
Human Molecular Genetics 2007 16(4):364-373; doi:10.1093/hmg/ddl456
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Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines
1 Genetic Epidemiology Group and 2 Human Genetics Laboratory, Queensland Institute of Medical Research, Herston, QLD 4029, Australia, 3 Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD 4076, 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, UK
* To whom correspondence should be addressed. Tel: +61 733620190; Fax: +61 733620101; Email: allan.mcrae{at}qimr.edu.au
Received July 4, 2006; Revised September 26, 2006; Accepted December 4, 2006
The expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an 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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.