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Sex-specific effects of the Huntington gene on normal neurodevelopment
Journal article   Open access   Peer reviewed

Sex-specific effects of the Huntington gene on normal neurodevelopment

Jessica K Lee, Yue Ding, Amy L Conrad, Elena Cattaneo, Eric Epping, Kathy Mathews, Pedro Gonzalez-Alegre, Larry Cahill, Vincent Magnotta, Bradley L Schlaggar, …
Journal of neuroscience research, Vol.95(1-2), pp.398-408
01/02/2017
DOI: 10.1002/jnr.23980
PMCID: PMC5729280
PMID: 27870408
url
http://doi.org/10.1002/jnr.23980View
Open Access

Abstract

Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain. Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease. © 2016 Wiley Periodicals, Inc.
Magnetic Resonance Imaging Brain - diagnostic imaging Humans Huntington Disease - pathology Male Brain - growth & development Sex Characteristics Intelligence - genetics Trinucleotide Repeats - genetics Brain - metabolism Huntington Disease - diagnostic imaging Neuropsychological Tests Young Adult Image Processing, Computer-Assisted Adolescent Huntington Disease - genetics Female Huntingtin Protein - genetics Child

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