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Human Molecular Genetics Advance Access published online on May 10, 2006
Human Molecular Genetics, 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.
Received March 6, 2006
Revised April 20, 2006
Accepted May 6, 2006

Article

Normal Variants of Microcephalin and ASPM Do Not Account for Brain Size Variability

Roger P. Woods 1 *, Nelson B. Freimer 2, Joseph A. De Young 3, Scott C. Fears 4, Nancy L. Sicotte 5, Susan K. Service 2, Daniel J. Valentino 6, Arthur W. Toga 6, and John C. Mazziotta 5

1 Ahmanson-Lovelace Brain Mapping Center, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA; Room 151, 660 Charles E. Young Drive South, Los Angeles, CA 90095, USA
2 Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA
3 Southern California Genotyping Consortium, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA
4 Ahmanson-Lovelace Brain Mapping Center, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA; Center for Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA
5 Ahmanson-Lovelace Brain Mapping Center, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA
6 Laboratory of Neuroimaging, David Geffen School of Medicine, University of California at Los Angeles, CA 90095, USA

* To whom correspondence should be addressed.
Roger P. Woods, E-mail: rwoods{at}ucla.edu


  Abstract

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 since 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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