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J Neurosci Res. 2017 Jan 2;95(1-2):398-408. doi: 10.1002/jnr.23980.

Sex-specific effects of the Huntington gene on normal neurodevelopment.

Author information

1
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
2
Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa.
3
Department of Biosciences, University of Milan, Milan, Italy.
4
Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
5
Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
6
Department of Neurobiology and Behavior, University of California, Irvine, California.
7
Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, Iowa.
8
Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.
9
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
10
Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri.
11
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri.
12
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.
13
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa.

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.

KEYWORDS:

Huntington disease; brain development; intelligence

PMID:
27870408
PMCID:
PMC5729280
DOI:
10.1002/jnr.23980
[Indexed for MEDLINE]
Free PMC Article

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