Titre du document / Document title

An optimistic view for quantifying mRNA in post-mortem human brain

Auteur(s) / Author(s)

PREECE Paul ⁽¹⁾ ; VIRLEY David J. ⁽²⁾ ; COSTANDI Moheb ⁽³⁾ ; COOMBES Robert ⁽⁴⁾ ; MOSS Stephen J. ⁽⁴⁾ ; MUDGE Anne W. ⁽⁴⁾ ; JAZIN Elena ⁽⁵⁾ ; CAIRNS Nigel J. ⁽⁶⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Quantuum, Departamento de Neurología, Rua das Branas 7-Bajo-D, 15177 Mera, A Coruña, ESPAGNE
⁽²⁾ Department of Neuroscience, Glaxo SmithKline Pharmaceuticals, New Frontiers Science Park, Harlow CM19 5AW, ROYAUME-UNI
⁽³⁾ MRC Centre for Developmental Neurobiology, Guys Hospital, Kings College London, London SE1 1UL, ROYAUME-UNI
⁽⁴⁾ MRC Laboratory of Molecular and Cellular Biology, University College London, London WC1E 6BT, ROYAUME-UNI
⁽⁵⁾ Departments of Medical Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 751 85, SUEDE
⁽⁶⁾ Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, 3600 Spruce Street, Philadelphia, PA 19104-4283, ETATS-UNIS

Résumé / Abstract

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.

Revue / Journal Title

Molecular brain research   ISSN 0169-328X 

Source / Source

2003, vol. 116, n^o1-2, pp. 7-16 [10 page(s) (article)] (35 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1986-2005) (Revue)

Mots-clés anglais / English Keywords

Degenerative disease ; Cerebral disorder ; Central nervous system disease ; Nervous system diseases ; Central nervous system ; Human ; Alzheimer disease ; Messenger RNA ; Quantitative analysis ; Postmortem ; Brain (vertebrata) ;

Mots-clés français / French Keywords

Maladie dégénérative ; Encéphale pathologie ; Système nerveux central pathologie ; Système nerveux pathologie ; Système nerveux central ; Homme ; Démence Alzheimer ; RNA messager ; Analyse quantitative ; Postmortem ; Encéphale ;

Mots-clés espagnols / Spanish Keywords

Enfermedad degenerativa ; Encéfalo patología ; Sistema nervosio central patología ; Sistema nervioso patología ; Sistema nervioso central ; Hombre ; Demencia Alzheimer ; RNA mensajero ; Análisis cuantitativo ; Postmortem ; Encéfalo ;

Mots-clés d'auteur / Author Keywords

Alzheimer's disease ; Human brain ; mRNA ; Quantification ; TaqMan ;

Localisation / Location

INIST-CNRS, Cote INIST : 12895 B, 35400011293850.0020