An optimistic view for quantifying mRNA in post-mortem human brain.
Quantitative human mRNA data are derived from post-mortem or biopsied tissue. RNA degradation, poor replication, a large mRNA variance and confounding factors such as brain pH and age of death are often cited, however, as objections to the data's reliability. A central question is whether post-mortem human mRNA can be treated as a statistically ordered system. TaqMan real-time RT-PCR was used to measure seven mRNAs in 513 cortical samples taken from 90 Alzheimer's disease and 81 control brains. Despite a high mRNA variance strong correlations were found between the mRNA transcripts in a single brain. Where a brain has a high/low level of one mRNA, the same brain invariably has a high/low level of other mRNAs; correlated order is present and allows removal of that source of variation common to all genes. Although levels of mRNA are highly variable between subjects (>1000-fold), quantitative order is present in post-mortem human mRNA, allowing effects due to pathology or gender to be isolated and tested for significance.
Preece
Paul
P
Quantuum, Departamento de Neurología, Rua das Branas 7-Bajo-D, 15177 Mera, A Coruña, Galicia, Spain. pablo@quantuum.com
Virley
David J
DJ
Costandi
Moheb
M
Coombes
Robert
R
Moss
Stephen J
SJ
Mudge
Anne W
AW
Jazin
Elena
E
Cairns
Nigel J
NJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001923:Brain Chemistry; D002102:Cadaver; D016022:Case-Control Studies; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D016014:Linear Models; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D011180:Postmortem Changes; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis* / Q000737:chemistry; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D019914:Taq Polymerase
D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C093596:amyloid beta-protein precursor 770 (301-323); D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D019914:Taq Polymerase