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Human Molecular Genetics Advance Access originally published online on May 10, 2006
Human Molecular Genetics 2006 15(12):2025-2029; doi:10.1093/hmg/ddl126
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© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Normal variants of Microcephalin and ASPM do not account for brain size variability

Roger P. Woods1,*, Nelson B. Freimer2, Joseph A. De Young3, Scott C. Fears1,2, Nancy L. Sicotte1, Susan K. Service2, Daniel J. Valentino4, Arthur W. Toga4 and John C. Mazziotta1

1Ahmanson-Lovelace Brain Mapping Center, 2Center for Neurobehavioral Genetics, Semel Institute, 3Southern California Genotyping Consortium, and 4Laboratory of Neuroimaging, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA

* To whom correspondence should be addressed at: Room 151, 660 Charles E. Young Drive South, Los Angeles, CA 90095, USA. Tel: +1 3107944057; Fax: +1 3107947406; Email: rwoods{at}ucla.edu

Received March 6, 2006; Revised April 20, 2006; Accepted May 6, 2006

Normal human brain volume is heritable. The genes responsible for variation in brain volume are not known. Microcephalin (MCPH1) and ASPM (abnormal spindle-like microcephaly associated) have been proposed as candidate genes as mutations in both genes are associated with microcephaly, and common variants of each gene are apparently under strong positive selective pressure. In 120 normal subjects, we genotyped these variants and measured brain volumes using magnetic resonance imaging. We found no evidence that the selected alleles were associated with increases or decreases in brain volume. This result suggests that the selective pressure on these genes may be related to subtle neurobiological effects or to their expression outside the brain.


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