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.
Sex-specific effects of the Huntington gene on normal neurodevelopment / J.K. Lee, Y. Ding, A.L. Conrad, E. Cattaneo, E. Epping, K. Mathews, P. Gonzalez-Alegre, L. Cahill, V. Magnotta, B.L. Schlaggar, J.S. Perlmutter, R.E.Y. Kim, J.D. Dawson, P. Nopoulos. - In: JOURNAL OF NEUROSCIENCE RESEARCH. - ISSN 0360-4012. - 95:1-2(2017), pp. 398-408.
|Titolo:||Sex-specific effects of the Huntington gene on normal neurodevelopment|
|Parole Chiave:||brain development; Huntington disease; intelligence; Adolescent; Brain; Child; Female; Humans; Huntingtin Protein; Huntington Disease; Image Processing, Computer-Assisted; Intelligence; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Trinucleotide Repeats; Young Adult; Sex Characteristics; Cellular and Molecular Neuroscience|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/jnr.23980|
|Appare nelle tipologie:||01 - Articolo su periodico|
File in questo prodotto:
|Lee_et_al-2017-Journal_of_Neuroscience_Research.pdf||Publisher's version/PDF||Administrator Richiedi una copia|