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PNAS 100 (15): 8993-8998

Copyright © 2003 by the National Academy of Sciences.

Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit

David J. Gerber*, Diana Hall{dagger}, Tsuyoshi Miyakawa*, Sandra Demars{dagger}, Joseph A. Gogos{ddagger}, Maria Karayiorgou{dagger},§,, and Susumu Tonegawa*,§,

*Howard Hughes Medical Institute, RIKEN/Massachusetts Institute of Technology Neuroscience Research Center, The Picower Center for Learning and Memory, Departments of Biology and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; {dagger}Human Neurogenetics Laboratory, The Rockefeller University, New York, NY 10021; and {ddagger}Department of Physiology and Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, NY 10032

Figure 1
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Fig. 1. PPP3CC gene locus. (A) The location of the PPP3CC gene in the 8p21.3 region is depicted in relation to relevant markers from linkage studies. D8S136 (13); D8S1771 (15, 16); D8S1752 (15); and D8S1715 and D8S133 (14). (B) An expanded view of the PPP3CC gene is presented, including the exon/intron structure and the locations of the SNPs used for our association studies and of the coding sequence mutation identified in exon 5. This mutation changes a G to an A at position 824 of the mRNA (GenBank accession no. NM_005605). Distances and positions in this figure are according to the November 2002 human draft sequence. (C) Haplotype distribution and transmission at the PPP3CC locus. Only four haplotypes with frequencies ≥5% were observed in both U.S. and SA samples and are shown here. The most common PPP3CC haplotype is consistently overtransmitted in both samples. T/nT, transmitted/nontransmitted.


Figure 2
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Fig. 2. PPP3CC expression in human brain. (A) PCR amplification of cDNA from human adult total brain, fetal total brain, and testis. PCR was performed on {approx}0.25 ng of cDNA with two primer pairs. Primer pair 1 amplifies a 218-bp fragment extending from exon 1 to exon 2. Primer pair 2 amplifies a 298-bp fragment from exon 14 consisting of 3' UTR sequence. Lane 1, 100-bp marker; lane 2, adult brain, primer pair 1; lane 3, adult brain, primer pair 2; lane 4, fetal brain, primer pair 1; lane 5, fetal brain, primer pair 2; lane 6, testis, primer pair 1; lane 7, testis, primer pair 2; lane 8, no DNA control, primer pair 1; lane 9, no DNA control, primer pair 2. The products <100 bp in size are present in lanes 8 and 9 and are most likely primer-related amplification artifacts. (B) PCR amplification of cDNA from human adult brain regions. PCR was performed on {approx}1.0 ng of cDNA with primer pair 1. Lane 1, 100-bp marker; lane 2, frontal lobe; lane 3, temporal lobe; lane 4, cerebellum; lane 5, hippocampus; lane 6, substantia nigra; lane 7, caudate nucleus; lane 8, amygdala; lane 9, thalamus; lane 10, hypothalamus; lane 11, pons; lane 12, medulla; lane 13, spinal cord.


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