The Journal of Neuroscience, March 4, 2009, 29(9):2867-2875; doi:10.1523/JNEUROSCI.5153-08.2009
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Behavioral/Systems/Cognitive
Identifying Heritable Brain Phenotypes in an Extended Pedigree of Vervet Monkeys
Scott C. Fears,5
William P. Melega,1
Susan K. Service,5
Chris Lee,2
Kelly Chen,2
Zhuowen Tu,6,7
Matthew J. Jorgensen,8
Lynn A. Fairbanks,3,5
Rita M. Cantor,4,5
Nelson B. Freimer,3,5 and
Roger P. Woods2
Departments of 1Molecular and Medical Pharmacology, 2Neurology, 3Psychiatry and Biobehavioral Sciences, and 4Human Genetics, 5Center for Neurobehavioral Genetics, University of California, Los Angeles (UCLA), Los Angeles, California 90095, 6Department of Neurology and 7Laboratory of Neuroimaging, UCLA, Los Angeles, California 90095-7334, and 8Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157
Correspondence should be addressed to Scott C. Fears, Center for Neurobehavioral Genetics, UCLA, 760 Westwood Plaza, Room C8-222, Los Angeles, CA 90024. Email: fears.scott{at}gmail.com
The area and volume of brain structural features, as assessed by high-resolution three-dimensional magnetic resonance imaging (MRI), are among the most heritable measures relating to the human CNS. We have conducted MRI scanning of all available monkeys >2 years of age (n = 357) from the extended multigenerational pedigree of the Vervet Research Colony (VRC). Using a combination of automated and manual segmentation we have quantified several correlated but distinct brain structural phenotypes. The estimated heritabilities (h2) for these measures in the VRC are higher than those reported previously for such features in humans or in other nonhuman primates: total brain volume (h2 = 0.99, SE = 0.06), cerebral volume (h2 = 0.98, SE = 0.06), cerebellar volume (h2 = 0.86, SE = 0.09), hippocampal volume (h2 = 0.95, SE = 0.07) and corpus callosum cross-sectional areas (h2 = 0.87, SE = 0.07). These findings indicate that, in the controlled environment and with the inbreeding structure of the VRC, additive genetic factors account for almost all of the observed variance in brain structure, and suggest the potential of the VRC for genetic mapping of quantitative trait loci underlying such variance.
Received Oct. 24, 2008;
revised Jan. 26, 2009;
accepted Jan. 28, 2009.
Correspondence should be addressed to Scott C. Fears, Center for Neurobehavioral Genetics, UCLA, 760 Westwood Plaza, Room C8-222, Los Angeles, CA 90024. Email: fears.scott{at}gmail.com
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A. J. Jasinska, S. Service, O.-w. Choi, J. DeYoung, O. Grujic, S.-y. Kong, M. J. Jorgensen, J. Bailey, S. Breidenthal, L. A. Fairbanks, et al.
Identification of brain transcriptional variation reproduced in peripheral blood: an approach for mapping brain expression traits
Hum. Mol. Genet.,
November 15, 2009;
18(22):
4415 - 4427.
[Abstract]
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