Selection of Reference Gene Expression in a Schizophrenia Brain Cohort-Reference-Cited by-同舟云学术

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

Published:2010-01 Issue:1 Volume:44 Page:59-70
ISSN:0004-8674
Container-title:Australian & New Zealand Journal of Psychiatry
language:en
Short-container-title:Aust N Z J Psychiatry

Author:

Weickert Cynthia Shannon¹,Sheedy Donna²,Rothmond Debora A.³,Dedova Irina⁴,Fung Samantha⁵,Garrick Therese²,Wong Jenny⁵,Harding Antony J.²,Sivagnanansundaram Sinthuja³,Hunt Clare²,Duncan Carlotta³,Sundqvist Nina⁴,Tsai Shan-Yuan³,Anand Jasna²,Draganic Daren⁶,Harper Clive²

Affiliation:

1. Schizophrenia Research Institute, Sydney, New South Wales, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; Schizophrenia Research Laboratory, Prince of Wales Medical Research Institute, SRL – 1st Floor, Corner of Barker and Easy Streets, Randwick, NSW 2031, Australia.

2. New South Wales Tissue Resource Centre, Department of Pathology, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia

3. Schizophrenia Research Institute, Sydney, New South Wales, Australia; Schizophrenia Research Laboratory, Prince of Wales Medical Research Institute, Randwick, New South Wales, Australia

4. Schizophrenia Research Institute, Sydney, New South Wales, Australia; New South Wales Tissue Resource Centre, Department of Pathology, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia

5. Schizophrenia Research Institute, Sydney, New South Wales, Australia; Schizophrenia Research Laboratory, Prince of Wales Medical Research Institute, Randwick, New South Wales, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

6. Schizophrenia Research Institute, Sydney, New South Wales, Australia

Abstract

Objective: In order to conduct postmortem human brain research into the neuropatho-logical basis of schizophrenia, it is critical to establish cohorts that are well-characterized and well-matched. The aim of the present study was therefore to determine if specimen characteristics including: diagnosis, age, postmortem interval (PMI), brain acidity (pH), and/or the agonal state of the subject at death related to RNA quality, and to determine the most appropriate reference gene mRNAs. Methods: A matched cohort was selected of 74 subjects (schizophrenia/schizoaffective disorder, n = 37; controls, n = 37). Middle frontal gyrus tissue was pulverized, tissue pH was measured, RNA isolated for cDNA from each case, and RNA integrity number (RIN) measurements were assessed. Using quantitative reverse transcription–polymerase chain reaction, nine housekeeper genes were measured and a geomean calculated per case in each diagnostic group. Results: The RINs were very good (mean = 7.3) and all nine housekeeper control genes were significantly correlated with RIN. Seven of nine housekeeper genes were also correlated with pH; two clinical variables, agonal state and duration of illness, did have an effect on some control mRNAs. No major impact of PMI or freezer time on housekeeper mRNAs was detected. The results show that people with schizophrenia had significantly less PPIA and SDHA mRNA and tended to have less GUSB and B2M mRNA, suggesting that these control genes may not be good candidates for normalization. Conclusions: In the present cohort <10% variability in RINs was detected and the diagnostic groups were well matched overall. The cohort was adequately powered (0.80–0.90) to detect mRNA differences (25%) due to disease. The study suggests that multiple factors should be considered in mRNA expression studies of human brain tissues. When schizophrenia cases are adequately matched to control cases subtle differences in gene expression can be reliably detected.

Publisher

SAGE Publications

Subject

Psychiatry and Mental health,General Medicine

Link

http://journals.sagepub.com/doi/pdf/10.3109/00048670903393662

Reference83 articles.

1. The Human Brain Revisited Opportunities and Challenges in Postmortem Studies of Psychiatric Disorders

2. Chapter 7 Brain banking and the human hypothalamus — factors to match for, pitfalls and potentials

3. Gene expression profiling in the post-mortem human brain — no cause for dismay

4. Microarray Technology: A Review of New Strategies to Discover Candidate Vulnerability Genes in Psychiatric Disorders

Cited by 99 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Transcriptional evidence of reduced BDNF trophic signalling capacity in the post-mortem human midbrain of schizophrenia cases with high inflammation;2024-09-03

2. Evidence for increased DNA damage repair in the postmortem brain of the high stress-response group of schizophrenia;Frontiers in Psychiatry;2023-08-22

3. The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain;Frontiers in Psychiatry;2023-07-14

4. Cytomegalovirus antibodies are associated with mood disorders, suicide, markers of neuroinflammation, and microglia activation in postmortem brain samples;Molecular Psychiatry;2023-06-30

5. GRIN2B gene expression is increased in the anterior cingulate cortex in major depression;Journal of Psychiatric Research;2023-04