RT Journal Article
SR Electronic
T1 Sex Chromosome Dosage Effects on Gene Expression in Humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 137752
DO 10.1101/137752
A1 Armin Raznahan
A1 Neelroop Parikshak
A1 Vijayendran Chandran
A1 Jonathan Blumenthal
A1 Liv Clasen
A1 Aaron Alexander-Bloch
A1 Andrew Zinn
A1 Danny Wangsa
A1 Jasen Wise
A1 Declan Murphy
A1 Patrick Bolton
A1 Thomas Ried
A1 Judith Ross
A1 Jay Giedd
A1 Daniel Geschwind
YR 2017
UL http://biorxiv.org/content/early/2017/05/14/137752.abstract
AB 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.