%0 Journal Article %A Armin Raznahan %A Neelroop Parikshak %A Vijayendran Chandran %A Jonathan Blumenthal %A Liv Clasen %A Aaron Alexander-Bloch %A Andrew Zinn %A Danny Wangsa %A Jasen Wise %A Declan Murphy %A Patrick Bolton %A Thomas Ried %A Judith Ross %A Jay Giedd %A Daniel Geschwind %T Sex Chromosome Dosage Effects on Gene Expression in Humans %D 2017 %R 10.1101/137752 %J bioRxiv %P 137752 %X A fundamental question in the biology of sex-differences has eluded direct study in humans: how does sex chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex chromosome aneuploidies (XO, XXX, XXY, XYY, XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity amongst evolutionarily preserved X-Y homologs, and revise prevailing theoretical models for SCD compensation by detecting X-linked genes whose expression increases with decreasing X- and/or Y- chromosome dosage. We further show that SCD-sensitive sex chromosome genes regulate specific co-expression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. Our findings detail wide-ranging effects of SCD on genome function with implications for human phenotypic variation. %U https://www.biorxiv.org/content/biorxiv/early/2017/05/14/137752.full.pdf