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examination of a minimally invasive blood sample, can provide biomarkers of
several different disease states. These profi les may be used for diagnostic, prognos-
tic and therapeutic evaluations and also provide a method for the evaluation of the
safety and effi cacy of various therapeutics. Gene expression fi ngerprints are useful
tools for monitoring exercise and training loads and thereby help to avoid training-
associated health risks.
There is marked alteration in WBC gene expression in animal models of injury
and infl ammation; the majority of the differentially expressed genes appear to be
uniquely associated with the type of injury and/or the infl ammatory stimulus.
Although some pathological states such as hypoxia may have direct impact on white
blood cells that is manifested by specifi c expression profi les, seemingly unrelated
events affecting various organs can markedly alter white blood cell gene expression
in a predictable, characteristic way that provides a novel approach to diagnosis of
diseases such as those involving the nervous system. Distinct human white blood
cell genomic profi les have been reported for the following neurological disorders:
- Neurofi bromatosis type 1, an autosomal dominant genetic disease caused by
mutations of the NF1 gene at chromosome 17q11.2. - Tourette’s syndrome
- Migraine
- Epilepsy patients being treated with valproic acid
- Stroke
Serial Analysis of Gene Expression
Serial analysis of gene expression (SAGE) technology was developed at the Johns
Hopkins University (Baltimore, MD) and licensed to Genzyme. Three principles
underlie the SAGE technology:
- One short oligonucleotide sequence from a defi ned location within a transcript
(“tag”) allows accurate quantitation - Tag size (10–14 bp) is optimal for high throughput while maintaining accurate
gene identifi cation and quantitation. - The combined power of serial and parallel processing increases data throughput
by orders of magnitude when compared to conventional expressed sequence
analysis.
Important uses of this test include the study of differences in gene expression
between cancer cells and their normal counterparts and identifi cation of genes that
may serve as useful diagnostic and prognostic markers. Differences in gene expres-
sion seen in SAGE translate directly into RNA differences as assessed by Northern
blot analysis, and alterations identifi ed in a few samples are consistent with data
from a larger sample of primary tumor isolates. Gene expression monitoring by
SAGE reduces the set of genes that are candidates for functional studies from tens
2 Molecular Diagnostics in Personalized Medicine