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New Study from Affymetrix Laboratories Points to Changing View of
How Genome Works
Any single base in genome can be transcribed into many different RNA sequences,
most of which never leave the nucleus
SANTA CLARA, Calif., March 24 /PRNewswire-FirstCall/ -- Scientists at
Affymetrix, Inc. (NASDAQ:AFFX) reported today in Science magazine online that
they have completed a high-resolution scan of structure and function for nearly
30 percent of the human genome sequence. In collaboration with the National
Cancer Institute, the research team used high-density GeneChip(R) microarrays
to study every fifth base, on average, of 10 human chromosomes; they found that
thousands of regions of the genome are transcribed into overlapping RNA
sequences and those sequences are separated by regions in which RNA is
transcribed more scarcely. All of the data is freely available at
http://transcriptome.affymetrix.com/publication/transcriptome_10chromosomes and
http://cgap.nci.nih.gov/Info/2005.1
"The findings of this study compel us to reconsider how the genome is organized
and regulated," said Thomas Gingeras, Vice President for Biological Research at
Affymetrix and senior author of the Science manuscript. "These data point us
toward two critical and exciting questions: What are the functions of these
previously unannotated transcripts and what are the regulation schemes that
orchestrate such complex assemblies of transcription? It seems certain that
this is not the genome we learned about while in school."
In the "traditional" view of the human genome, there are about 26,000 genes
used to make proteins that ultimately control the structure and function of
every cell in the body. Most disease research has focused on studying these
protein-coding genes, even though they make up only about two percent of the
human genome sequence.
The new study by Gingeras' team did not make any assumption of what parts of
the genome might or might not be important to human biology. They used new
Affymetrix tiling microarrays and unique biochemical tests to scan the sequence
of 10 human chromosomes -- one third of the human genome sequence -- and found
that roughly 15 percent of the DNA sequence analyzed was transcribed; most
sites of transcription were not located in areas associated with protein-coding
genes.
The team found many diverse kinds of RNAs transcribed from distinct regions of
the genome, creating a complex pool of overlapping transcription. While the
team validated many known protein-coding transcripts that contribute to this
complex pool, they also discovered that:
-- Seventy-five percent of all of the RNA that were exclusively found in
the nucleus had not been previously detected.
-- Any single base in the genome can be transcribed into several different
transcripts with different, but overlapping sequences. Often,
transcripts from one strand of DNA can share parts of their sequence
with overlapping transcripts from the same strand or even from the
opposite strand (antisense).
-- Transcripts missing a run of adenosine nucleotides (non-polyA) at the
tail-end were twice as common as the more well-studied RNAs that have
this sequence. Most transcripts derived from the sparsely transcribed
regions between centers of dense transcription are non-polyA
transcripts.
This study focused on an in depth scan of 10 chromosomes; however, Affymetrix
has developed tiling microarrays that cover all human chromosomes. GeneChip
tiling microarrays have been used by Gingeras and his collaborators, as well as
the NHGRI publicly funded ENCODE project, to study the human genome in an
unbiased fashion -- including regions that have historically been termed coding
and non-coding.
Affymetrix is now beginning to commercialize tiling microarrays to give the
research community the ability to perform these types of unbiased studies as
well. By focusing research beyond the parts of the genome that have been
traditionally studied, scientists hope to discover new drug targets, new
biomarkers, and a better understanding of disease mechanism.
This project has been funded in whole or in part with Federal Funds from the
National Cancer Institute, National Institutes of Health, under Contract number
N01-CO-12400.
About Tiling Arrays:
Affymetrix "tiling" arrays mark a shift in the way microarrays are designed and
interpreted. By using a neutral approach to array design, tiling arrays
include all non-repetitive sequence from a given genome, not just the
hand-selected regions that were previously thought to be important. With the
inclusion of all genomic sequences, microarrays can now be used as a discovery
tool to generate annotations and discover new transcripts. In late 2005,
Affymetrix plans to launch high-resolution tiling arrays for the entire human
genome and several model organisms, including Drosophila, Arabidopsis, S.
cerevisiae and S. pombe.
Further Information:
Using GeneChip(R) technology to study all human transcripts (Transcriptome) --
http://www.affymetrix.com/transcriptome/
Using Affymetrix tiling arrays in the ENCODE project --
http://www.affymetrix.com/products/arrays/specific/encode.affx
Using tiling arrays to discover new transcripts in Arabidopsis --
http://www.affymetrix.com/community/wayahead/beyond_arabidopsis.affx
Using tiling arrays to map new human transcription factor binding sites --
http://www.affymetrix.com/community/wayahead/exploring_human_genome.affx
About Affymetrix
Affymetrix scientists invented the world's first microarray in 1989 and began
selling the first commercial microarray in 1994. Since then, Affymetrix
GeneChip(R) technology has become the industry standard in molecular biology
research. Affymetrix technology is used by the world's top pharmaceutical,
diagnostic and biotechnology companies as well as leading academic, government
and not-for-profit research institutes. More than 1,200 systems have been
shipped around the world and over 3,000 peer-reviewed papers have been
published using the technology. Affymetrix' patented photolithographic
manufacturing process provides the most information capacity available today on
an array, enabling researchers to use a whole-genome approach to analyze the
relationship between genetics and health. Affymetrix is headquartered in Santa
Clara, Calif., with manufacturing facilities in Sacramento, Calif., and
Bedford, Mass. The company maintains important sales and marketing operations
in Europe and Asia and has about 900 employees worldwide.
All statements in this press release that are not historical are "forward-
looking statements" within the meaning of Section 21E of the Securities
Exchange Act as amended, including statements regarding Affymetrix'
"expectations," "beliefs," "hopes," "intentions," "strategies" or the like.
Such statements are subject to risks and uncertainties that could cause actual
results to differ materially for Affymetrix from those projected, including,
but not limited to risks of the Company's ability to achieve and sustain higher
levels of revenue, higher gross margins, reduced operating expenses,
uncertainties relating to technological approaches, manufacturing, product
development (including uncertainties relating to the use of the tiling arrays
and outcome of research discussed in this press release), personnel retention,
uncertainties related to cost and pricing of Affymetrix products, dependence on
collaborative partners, uncertainties relating to sole source suppliers,
uncertainties relating to FDA and other regulatory approvals, competition,
risks relating to intellectual property of others and the uncertainties of
patent protection and litigation. These and other risk factors are discussed in
Affymetrix' Form 10-K for the year ended December 31, 2004 and other SEC
reports, including its Quarterly Reports on Form 10-Q for subsequent quarterly
periods. Affymetrix expressly disclaims any obligation or undertaking to
release publicly any updates or revisions to any forward-looking statements
contained herein to reflect any change in Affymetrix' expectations with regard
thereto or any change in events, conditions, or circumstances on which any such
statements are based.
NOTE: Affymetrix, the Affymetrix logo, and GeneChip are registered trademarks
owned or used by Affymetrix, Inc.
DATASOURCE: Affymetrix, Inc.
CONTACT: Media: Wes Conard, Director, Public Relations, +1-408-731-5791,
or, Investors: Doug Farrell, Vice President, Investor Relations,
+1-408-731-5285, both of Affymetrix
Web site: http://www.affymetrix.com/