TY - JOUR
T1 - Primate disrupted-in-schizophrenia-1 (DISC1)
T2 - High divergence of a gene for major mental illnesses in recent evolutionary history
AU - Bord, Lyuda
AU - Wheeler, Jeff
AU - Paek, Matthew
AU - Saleh, Masoumeh
AU - Lyons-Warren, Ariel
AU - Ross, Christopher A.
AU - Sawamura, Naoya
AU - Sawa, Akira
N1 - Funding Information:
We thank Mr. J. Kleiderlein and Dr. Takako Yamamoto-Sawamura for technical assistance, and Ms. Y. Lema for preparation of the figures. We thank Dr. Pamela Talalay for critical reading of this manuscript, and Dr. Tim Moran for providing us with a monkey brain and for helpful suggestions. We thank Dr. Toshifumi Tomoda for discussing the sequence analysis. This paper was supported by grants from U.S. Public Health Service Grant MH-69853 (AS) as well as foundation grants from Stanley, NARSAD and S-R (AS).
PY - 2006/11
Y1 - 2006/11
N2 - Here we analyze the species conservation of disrupted-in-schizophrenia-1 (DISC1) gene, a susceptibility gene for schizophrenia. We cloned cDNA of DISC1 and characterized DISC1 protein in monkey brains and compared their features with those in a variety of species, including humans, rodents and lower vertebrates. Sequences of human and monkey DISC1 are very similar for both nucleotides and amino acids, in sharp contrast to those of rodents; this is reminiscent of G72, another gene involved in major mental illnesses. Bioinformatic cross-species comparisons identified a portion of DISC1 sequences in chicken and Caenorhabditis elegans, but failed to find DISC1 in Drosophila. In contrast to sequence differences, the regional expression profile of DISC1 is well conserved between rodents and primates in that levels of DISC1 mRNA and protein are higher in the hippocampus and the cerebral cortex, and much lower in cerebellum in adult brains. The findings of this study may suggest overall patterns of evolution of genes for psychiatric disorders, and thus assist in production of genetically-engineered mice, and the interpretation of the underlying mechanisms of psychiatric conditions.
AB - Here we analyze the species conservation of disrupted-in-schizophrenia-1 (DISC1) gene, a susceptibility gene for schizophrenia. We cloned cDNA of DISC1 and characterized DISC1 protein in monkey brains and compared their features with those in a variety of species, including humans, rodents and lower vertebrates. Sequences of human and monkey DISC1 are very similar for both nucleotides and amino acids, in sharp contrast to those of rodents; this is reminiscent of G72, another gene involved in major mental illnesses. Bioinformatic cross-species comparisons identified a portion of DISC1 sequences in chicken and Caenorhabditis elegans, but failed to find DISC1 in Drosophila. In contrast to sequence differences, the regional expression profile of DISC1 is well conserved between rodents and primates in that levels of DISC1 mRNA and protein are higher in the hippocampus and the cerebral cortex, and much lower in cerebellum in adult brains. The findings of this study may suggest overall patterns of evolution of genes for psychiatric disorders, and thus assist in production of genetically-engineered mice, and the interpretation of the underlying mechanisms of psychiatric conditions.
KW - DISC1
KW - Evolution
KW - Primates
KW - Rodents
KW - Schizophrenia
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U2 - 10.1016/j.neures.2006.07.010
DO - 10.1016/j.neures.2006.07.010
M3 - Article
C2 - 16965828
AN - SCOPUS:33750011578
SN - 0168-0102
VL - 56
SP - 286
EP - 293
JO - Neuroscience Research
JF - Neuroscience Research
IS - 3
ER -