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News Release from: Agilent Technologies Europe | Subject: Agilent microarrays
Edited by the Laboratorytalk Editorial
Team on 18 January 2008
Microarrays in genomic error mechanism
discovery
Researchers at Baylor College of Medicine, Texas, have observed a unique way that DNA additions or deletions associated with a wide range of diseases are introduced in genes during cell division.
These types of 'errors' have been associated with Alzheimer's, Parkinson's, Potocki-Lupski Syndrome and other developmental and neurological disorders Custom Agilent oligonucleotide comparative genomic hybridisation microarrays played a key role in the discovery
This article was originally published on Laboratorytalk on 22 Dec 2006 at 8.00am (UK)
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The article, A DNA replication mechanism for generating nonrecurrent rearrangements associated with genomic disorders, in the current issue of the journal Cell, describes a newly discovered mechanism for human genomic disorders called replication Fork Stalling and Template Switching (Fostes) in which segments of DNA are added or deleted in previously unexpected locations during replication.
"We're very pleased to provide tools with the flexibility, sensitivity and resolution to enable this breakthrough research," said Condie Carmack, marketing manager, Agilent.
"The Baylor team needed total control over the sequences on their microarrays as well as very high sensitivity and precision to make this research work.
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"Our SurePrint in-situ synthesis platform is particularly well-suited for this type of work".
"The Agilent microarrays were essential in enabling us to elucidate this novel mechanism," said BCM's James Lupski, Cullen professor of molecular and human genetics, the senior investigator of this report.
When a DNA addition or deletion occurs in the wrong place, a genomic-based disorder like Pelizaeus-Merzbacher disease (PMD) can occur.
PMD is a progressive degenerative disorder of the central nervous system in which motor abilities and intellectual function deteriorate.
This X-linked neurodeelopment disorder affects males and can have particularly devastating consequences.
Jennifer Lee, the lead author and a member of the team, was studying PMD and found genomic changes that previous theories about DNA recombination did not explain.
In some places, extra genetic material was found in the middle of another duplication.
Baylor's Fostes mechanism explains this, Lupski points out.
Lupski pioneered the emerging field of copy number variation (CNV) in the early 1990s in the quest to understand genetic variation and the multiple molecular mechanism for disease.
Now, he and his colleagues have discovered that the DNA replication process can stall, and sometimes, switch to a different 'template' rather than restarting in the same place.
In addition to disease research, Lupski says the Fostes mechanism could also play an important role in studies probing human evolution.
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