title: Globally Divergent but Locally Convergent X- and Y-Chromosome Influences on Cortical Development.
abstract: Owing to their unique evolutionary history, modern mammalian X- and Y-chromosomes have highly divergent gene contents counterbalanced by regulatory features, which preferentially restrict expression of X- and Y-specific genes. These 2 characteristics make opposing predictions regarding the expected dissimilarity of X- vs. Y-chromosome influences on biological structure and function. Here, we quantify this dissimilarity using in vivo neuroimaging within a rare cohort of humans with diverse sex chromosome aneuploidies (SCAs). We show that X- and Y-chromosomes have opposing effects on overall brain size but exert highly convergent influences on local brain anatomy, which manifest across biologically distinct dimensions of the cerebral cortex. Large-scale online meta-analysis of functional neuroimaging data indicates that convergent sex chromosome dosage effects preferentially impact centers for social perception, communication, and decision-making. Thus, despite an almost complete lack of sequence homology, and opposing effects on overall brain size, X- and Y-chromosomes exert congruent effects on the proportional size of cortical systems involved in adaptive social functioning. These convergent X-Y effects (i) track the dosage of those few genes that are still shared by X- and Y-chromosomes, and (ii) may provide a biological substrate for the link between SCA and increased rates of psychopathology.
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Armin
authors.initials: A
authors.lastname: Raznahan
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Nancy Raitano
authors.initials: NR
authors.lastname: Lee
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Deanna
authors.initials: D
authors.lastname: Greenstein
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA Department of Speech and Hearing Sciences, George Washington University, Washington, DC 20052 USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Wallace
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Blumenthal
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Liv S
authors.initials: LS
authors.lastname: Clasen
authors.affiliation: Section on Brain Imaging, Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Jay N
authors.initials: JN
authors.lastname: Giedd
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D001921:Brain / Q000033:anatomy & histology*; D002648:Child; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult
keywords: aneuploidy; cortical thickness; pseudoautosomal; surface area