Influence of sex and genetic variability on expression of X-linked genes in human monocytes

• Published in: Genomics (San Diego, Calif.) Vol. 98; no. 5; pp. 320 - 326
• Main Authors: Castagné, Raphaële, Zeller, Tanja, Rotival, Maxime, Szymczak, Silke, Truong, Vinh, Schillert, Arne, Trégouët, David-Alexandre, Münzel, Thomas, Ziegler, Andreas, Cambien, François, Blankenberg, Stefan, Tiret, Laurence
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.2011; Elsevier
• Subjects: Adult; Aged; autosomes; Biological and medical sciences; Calcium-Binding Proteins; Calcium-Binding Proteins - genetics; Chromosomes, Human, X; Chromosomes, Human, X - genetics; cytology; Diverse techniques; Expression Quantitative Trait Locus; Female; females; Fundamental and applied biological sciences. Psychology; Gender; Gene expression; genes; Genes, X-Linked; Genes. Genome; Genetic Variation; genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Humans; Male; males; microarray technology; Middle Aged; Molecular and cellular biology; Molecular genetics; monocytes; Monocytes - cytology; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Sex Factors; Transcription, Genetic; X Chromosome Inactivation; LCL; SNP; X chromosome inactivation; eQTL; Gender; Gene expression; Expression Quantitative Trait Locus; XCI; Human; Sex linked character; Genetic variability; Monocyte; Genomics; Sex; Inactivation; eQTL marker; Gene; X-Chromosome
• ISSN: 0888-7543; 1089-8646; 1089-8646
• DOI: 10.1016/j.ygeno.2011.06.009

In humans, the fraction of X-linked genes with higher expression in females has been estimated to be 5% from microarray studies, a proportion lower than the 25% of genes thought to escape X inactivation. We analyzed 715 X-linked transcripts in circulating monocytes from 1,467 subjects and found an excess of female-biased transcripts on the X compared to autosomes (9.4% vs 5.5%, p < 2 × 10 −5). Among the genes not previously known to escape inactivation, the most significant one was EFHC2 whose 20% of variability was explained by sex. We also investigated cis expression quantitative trait loci (eQTLs) by analyzing 15,703 X-linked SNPs. The frequency and magnitude of X-linked cis eQTLs were quite similar in males and females. Few genes exhibited a stronger genetic effect in females than in males ( ARSD, DCX, POLA1 and ITM2A). These genes would deserve further investigation since they may contribute to sex pathophysiological differences.