Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines

Hum Mol Genet. 2007 Feb 15;16(4):364-73. doi: 10.1093/hmg/ddl456. Epub 2006 Dec 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line, Transformed*
  • Cell Transformation, Viral
  • Databases, Factual
  • Family
  • Female
  • Gene Expression Regulation*
  • Genotype*
  • Humans
  • Lymphocytes / metabolism*
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Sex Characteristics*
  • Twins, Monozygotic