Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. Many genes implicated in these processes may be present in low abundance in the human brain. DNA microarray analysis identifies changed...

Full description

Bibliographic Details
Main Authors: Walker P Roy, Lach Boleslaw, Shen Hui, Lei Joy X, Ribecco-Lutkiewicz Maria, Malek Lawrence T, Sooknanan Roy R, Liu Qing, Martin Joel, Sikorska Marianna
Format: Article
Language:English
Published: BMC 2006-11-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/7/286
_version_ 1818641545406971904
author Walker P Roy
Lach Boleslaw
Shen Hui
Lei Joy X
Ribecco-Lutkiewicz Maria
Malek Lawrence T
Sooknanan Roy R
Liu Qing
Martin Joel
Sikorska Marianna
author_facet Walker P Roy
Lach Boleslaw
Shen Hui
Lei Joy X
Ribecco-Lutkiewicz Maria
Malek Lawrence T
Sooknanan Roy R
Liu Qing
Martin Joel
Sikorska Marianna
author_sort Walker P Roy
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. Many genes implicated in these processes may be present in low abundance in the human brain. DNA microarray analysis identifies changed genes that are expressed at high or moderate levels. Complementary to this approach, we described here a novel technology designed specifically to isolate rare and novel genes previously undetectable by other methods. We have used this method to identify differentially expressed genes in brains affected by AD. Our method, termed Subtractive Transcription-based Amplification of mRNA (STAR), is a combination of subtractive RNA/DNA hybridization and RNA amplification, which allows the removal of non-differentially expressed transcripts and the linear amplification of the differentially expressed genes.</p> <p>Results</p> <p>Using the STAR technology we have identified over 800 differentially expressed sequences in AD brains, both up- and down- regulated, compared to age-matched controls. Over 55% of the sequences represent genes of unknown function and roughly half of them were novel and rare discoveries in the human brain. The expression changes of nearly 80 unique genes were further confirmed by qRT-PCR and the association of additional genes with AD and/or neurodegeneration was established using an in-house literature mining tool (LitMiner).</p> <p>Conclusion</p> <p>The STAR process significantly amplifies unique and rare sequences relative to abundant housekeeping genes and, as a consequence, identifies genes not previously linked to AD. This method also offers new opportunities to study the subtle changes in gene expression that potentially contribute to the development and/or progression of AD.</p>
first_indexed 2024-12-16T23:28:52Z
format Article
id doaj.art-0dede9f7ea5245f6bf5230f71a305152
institution Directory Open Access Journal
issn 1471-2164
language English
last_indexed 2024-12-16T23:28:52Z
publishDate 2006-11-01
publisher BMC
record_format Article
series BMC Genomics
spelling doaj.art-0dede9f7ea5245f6bf5230f71a3051522022-12-21T22:11:56ZengBMCBMC Genomics1471-21642006-11-017128610.1186/1471-2164-7-286Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brainsWalker P RoyLach BoleslawShen HuiLei Joy XRibecco-Lutkiewicz MariaMalek Lawrence TSooknanan Roy RLiu QingMartin JoelSikorska Marianna<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is a complex disorder that involves multiple biological processes. Many genes implicated in these processes may be present in low abundance in the human brain. DNA microarray analysis identifies changed genes that are expressed at high or moderate levels. Complementary to this approach, we described here a novel technology designed specifically to isolate rare and novel genes previously undetectable by other methods. We have used this method to identify differentially expressed genes in brains affected by AD. Our method, termed Subtractive Transcription-based Amplification of mRNA (STAR), is a combination of subtractive RNA/DNA hybridization and RNA amplification, which allows the removal of non-differentially expressed transcripts and the linear amplification of the differentially expressed genes.</p> <p>Results</p> <p>Using the STAR technology we have identified over 800 differentially expressed sequences in AD brains, both up- and down- regulated, compared to age-matched controls. Over 55% of the sequences represent genes of unknown function and roughly half of them were novel and rare discoveries in the human brain. The expression changes of nearly 80 unique genes were further confirmed by qRT-PCR and the association of additional genes with AD and/or neurodegeneration was established using an in-house literature mining tool (LitMiner).</p> <p>Conclusion</p> <p>The STAR process significantly amplifies unique and rare sequences relative to abundant housekeeping genes and, as a consequence, identifies genes not previously linked to AD. This method also offers new opportunities to study the subtle changes in gene expression that potentially contribute to the development and/or progression of AD.</p>http://www.biomedcentral.com/1471-2164/7/286
spellingShingle Walker P Roy
Lach Boleslaw
Shen Hui
Lei Joy X
Ribecco-Lutkiewicz Maria
Malek Lawrence T
Sooknanan Roy R
Liu Qing
Martin Joel
Sikorska Marianna
Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains
BMC Genomics
title Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains
title_full Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains
title_fullStr Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains
title_full_unstemmed Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains
title_short Novel subtractive transcription-based amplification of mRNA (STAR) method and its application in search of rare and differentially expressed genes in AD brains
title_sort novel subtractive transcription based amplification of mrna star method and its application in search of rare and differentially expressed genes in ad brains
url http://www.biomedcentral.com/1471-2164/7/286
work_keys_str_mv AT walkerproy novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT lachboleslaw novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT shenhui novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT leijoyx novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT ribeccolutkiewiczmaria novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT maleklawrencet novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT sooknananroyr novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT liuqing novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT martinjoel novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains
AT sikorskamarianna novelsubtractivetranscriptionbasedamplificationofmrnastarmethodanditsapplicationinsearchofrareanddifferentiallyexpressedgenesinadbrains