title: Sex-specific effects of the Huntington gene on normal neurodevelopment.
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.
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Conrad
authors.affiliation: Department of Biosciences, University of Milan, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cattaneo
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Eric
authors.initials: E
authors.lastname: Epping
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.|Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Kathy
authors.initials: K
authors.lastname: Mathews
authors.affiliation: Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez-Alegre
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, California.
authors.forename: Larry
authors.initials: L
authors.lastname: Cahill
authors.affiliation: Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magnotta
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.|Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.|Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri.|Department of Neurology, Washington University School of Medicine, St. Louis, Missouri.|Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Schlaggar
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.|Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri.|Department of Neurology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Perlmutter
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Regina E Y
authors.initials: RE
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Dawson
authors.affiliation: Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.|Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.|Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Peg
authors.initials: P
authors.lastname: Nopoulos
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000378:metabolism*; D002648:Child; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics*; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D007360:Intelligence / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D012727:Sex Characteristics; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein
keywords: Huntington disease; brain development; intelligence