Human Molecular Genetics Advance Access originally published online on August 19, 2009
Human Molecular Genetics 2009 18(22):4415-4427; doi:10.1093/hmg/ddp397
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Identification of brain transcriptional variation reproduced in peripheral blood: an approach for mapping brain expression traits
1 Center for Neurobehavioral Genetics and 2 Department of Psychology, University of California, Los Angeles, CA, USA, 3 Department of Pathology, Section on Comparative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA and 4 Departments of Neurology and Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
* To whom correspondence should be addressed at: UCLA Center for Neurobehavioral Genetics, Gonda Center, Room 3506, 695 Charles E. Young Drive South, PO Box 951761, Los Angeles, CA 90095, USA. Tel: +1 3107949571; Fax: +1 3107949613; Email: nfreimer{at}mednet.ucla.edu
Received May 4, 2009; Accepted August 17, 2009
Genome-wide gene expression studies may provide substantial insight into gene activities and biological pathways differing between tissues and individuals. We investigated such gene expression variation by analyzing expression profiles in brain tissues derived from eight different brain regions and from blood in 12 monkeys from a biomedically important non-human primate model, the vervet (Chlorocebus aethiops sabaeus). We characterized brain regional differences in gene expression, focusing on transcripts for which inter-individual variation of expression in brain correlates well with variation in blood from the same individuals. Using stringent criteria, we identified 29 transcripts whose expression is measurable, stable, replicable, variable between individuals, relevant to brain function and heritable. Polymorphisms identified in probe regions could, in a minority of transcripts, confound the interpretation of the observed inter-individual variation. The high heritability of levels of these transcripts in a large vervet pedigree validated our approach of focusing on transcripts that showed higher inter-individual compared with intra-individual variation. These selected transcripts are candidate expression Quantitative Trait Loci, differentially regulating transcript levels in the brain among individuals. Given the high degree of conservation of tissue expression profiles between vervets and humans, our findings may facilitate the understanding of regional and individual transcriptional variation and its genetic mechanisms in humans. The approach employed here—utilizing higher quality tissue and more precise dissection of brain regions than is usually possible in humans—may therefore provide a powerful means to investigate variation in gene expression relevant to complex brain related traits, including human neuropsychiatric diseases.