Comparative proteome analysis of the hippocampus implicates chromosome 6q in schizophrenia

被引:79
作者
Edgar, PF
Douglas, JE
Cooper, GJS
Dean, B
Kydd, R
Faull, RLM
机构
[1] Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand
[2] Univ Auckland, Dept Psychiat & Behav Sci, Auckland 1, New Zealand
[3] Univ Auckland, Dept Anat Radiol, Auckland 1, New Zealand
关键词
collapsin response mediator protein 2; diazepam binding inhibitor; manganese superoxide dismutase; segregation distortion; T-complex protein 1; two-dimensional gel electrophoresis;
D O I
10.1038/sj.mp.4000580
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Comparative brain proteome analysis is a new strategy to discover proteins and therefore genes whose altered expression may underlie schizophrenia. This strategy does not require an a priori theory of the pathogenesis or the mode of inheritance of schizophrenia. Using proteome analysis we previously compared the hippocampal proteome, that is, those proteins expressed by the hippocampal genome, of seven schizophrenic individuals with the hippocampal proteome of seven control individuals, matched for age and post mortem delay.(1) We found 18 proteins that were significantly altered in concentration in the schizophrenic hippocampus (P < 0.05), when compared to control tissue. One of these proteins was characterised, by N-terminal sequencing, as diazepam binding inhibitor whose gene maps to 6q12-q21. Here we characterise a further three of the 18 proteins as: manganese superoxide dismutase, 6q25.3, T-complex protein 1, 6q25,3-q26 and collapsin response mediator protein 2, 8p21. That three of these four characterised proteins should map to the long arm of the same chromosome is significant (P < 0.002) and suggests the importance of chromosome 6q in schizophrenia. These results indicate that antioxidant defence is altered in the schizophrenic hippocampus and suggest that segregation distortion, of schizophrenia susceptibility genes, may be a possible causative factor in the high incidence of schizophrenia.
引用
收藏
页码:85 / 90
页数:6
相关论文
共 30 条
[1]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[2]   Cognitive impairment in elderly schizophrenia: A dementia (still) lacking distinctive histopathology [J].
Arnold, SE ;
Trojanowski, JQ .
SCHIZOPHRENIA BULLETIN, 1996, 22 (01) :5-9
[3]   Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees [J].
Cao, QH ;
Martinez, M ;
Zhang, J ;
Sanders, AR ;
Badner, JA ;
Cravchik, A ;
Markey, CJ ;
Beshah, E ;
Guroff, JJ ;
Maxwell, ME ;
Kazuba, DM ;
Whiten, R ;
Goldin, LR ;
Gershon, ES ;
Gejman, PV .
GENOMICS, 1997, 43 (01) :1-8
[4]   DIAZEPAM BINDING INHIBITOR (DBI) - A PEPTIDE WITH MULTIPLE BIOLOGICAL ACTIONS [J].
COSTA, E ;
GUIDOTTI, A .
LIFE SCIENCES, 1991, 49 (05) :325-344
[5]   MAJOR HISTOCOMPATIBILITY COMPLEX, T-COMPLEX, AND LEUKEMIA [J].
DORAK, MT ;
BURNETT, AK .
CANCER CAUSES & CONTROL, 1992, 3 (03) :273-282
[6]   A comparative proteome analysis of hippocampal tissue from schizophrenic and Alzheimer's disease individuals [J].
Edgar, PF ;
Schonberger, SJ ;
Dean, B ;
Faull, RLM ;
Kydd, R ;
Cooper, GJS .
MOLECULAR PSYCHIATRY, 1999, 4 (02) :173-178
[7]   REPRODUCTIVE RATES IN FAMILIES OF SCHIZOPHRENIC-PATIENTS IN A CASE-CONTROL STUDY [J].
FANANAS, L ;
BERTRANPETIT, J .
ACTA PSYCHIATRICA SCANDINAVICA, 1995, 91 (03) :202-204
[8]   MAPPING OF THE SOD-2 LOCUS INTO THE T-COMPLEX ON MOUSE CHROMOSOME-17 [J].
FIGUEROA, F ;
VINCEK, V ;
KASAHARA, M ;
BELL, GI ;
KLEIN, J .
IMMUNOGENETICS, 1988, 28 (04) :260-264
[9]   Oestrogen and mental state [J].
Fink, G ;
Sumner, BEH .
NATURE, 1996, 383 (6598) :306-306
[10]   ELEVATED RISKS FOR AMYOTROPHIC-LATERAL-SCLEROSIS AND BLOOD DISORDERS IN ASHKENAZI SCHIZOPHRENIC PEDIGREES SUGGEST NEW CANDIDATE GENES IN SCHIZOPHRENIA [J].
GOODMAN, AB .
AMERICAN JOURNAL OF MEDICAL GENETICS, 1994, 54 (03) :271-278