-
- SEATTLE - A Fred Hutchinson Cancer Research Center geneticist asserts
in the June issue of Nature Genetics that building a detailed map of the
human genome will take significantly more time and resources than previously
estimated.
-
- While current gene-mapping efforts target
the identification of 400,000 genetic markers to help locate common disease
genes, many more such signposts must be found before the map can be considered
a truly useful tool for pharmaceutical research and development, says the
paper's author, Dr. Leonid Kruglyak. "An essential issue yet to be
settled is the required marker density for such maps," writes Kruglyak,
an associate member of the Hutchinson Center's divisions of Human Biology
and Public Health Sciences.
-
- Kruglyak predicts researchers instead
will need to locate at least half a million such "mile markers"along
the DNA highway if geneticists are to stay on track when chasing down genes
that influence characteristics such as disease susceptibility and drug
response.
-
- "People may be disappointed in my
conclusion, because it implies we're going to have to work that much harder,
but it is simply a prediction for what resources will actually be needed
to accomplish the task ahead of us," says Kruglyak, an expert in using
powerful statistical and computational tools to tease out genetic components
of common "diseases of civilization" such as cancer and heart
disease.
-
- "The technology for doing this -
typing potentially thousands of individuals for half a million genetic
markers - really needs to be developed much further than where it is today,"
he says.
-
- The publication of Kruglyak's paper comes
on the heels of the establishment of the SNP Consortium, an unprecedented
collaboration between industry and academia to create a finely detailed
map of the human genome. Comprised of 10 of the world's largest drug companies,
a major British charity and a handful of academic genetics laboratories,
this nonprofit alliance, announced in April, seeks to build on and ultimately
accelerate the efforts of the federally funded Human Genome Project.
-
- While the Human Genome Project aims to
assemble a common, "one-size-fits-all" map of human DNA sequence
by the year 2003, the drug-company consortium plans to take the genetic
decoding effort a step further. Its goal: to create a more detailed genetic
blueprint that can be used by pharmaceutical companies to tailor medications
to a person's unique genetic inheritance - a radical departure from today's
blanket approach to drug design.
-
- To accomplish this task, the consortium
plans to locate, within the next two years, 300,000 of the estimated 2
million single-nucleotide polymorphisms, or SNPs, that pepper the human
genome. SNPs (pronounced "snips") are minute, usually functionless
single-letter variations within the genetic code that serve as markers,
or signposts, to help locate common disease genes. The Human Genome Project,
in contrast, seeks to isolate just 100,000 such markers.
-
- While together these efforts represent
a sound start for building a complete, high-density picture of the complete
human DNA sequence, even more genetic markers must be found, says Kruglyak,
also a professor of genetics and molecular biotechnology at the University
of Washington.
-
- But far from being pessimistic, Kruglyak
views the undertaking with much enthusiasm and hope.
-
- "Having a more finely tuned outline
of the human genome in hand ultimately will shed light on what makes each
person genetically unique and thus particularly vulnerable to certain diseases
or immune to certain drugs," he says. Also in the Nature Genetics
article, Kruglyak addresses the inherent limitations of mining so-called
"isolated" human populations, such as that of Iceland, for disease
genes.
-
- Since Iceland essentially has had no
immigration since the Vikings landed in the ninth century, geneticists
widely presumed the DNA of its inhabitants would be relatively undisturbed,
free of the genetic "static" commonly seen in more culturally
diverse populations. With less background noise, it was presumed that gene
hunters could more easily zero in on their prey.
-
- "For geneticists, part of the appeal
of isolated populations such as Iceland was that you might be able to get
away with a much looser genetic map containing fewer SNPs, or genetic markers,"
he says. "However, my research shows that in regions surrounding common
genetic mutations, the DNA from Iceland looks exactly the same as that
from larger populations, requiring an equally dense map of SNPs to detect
an association between a marker and disease."
-
- To be truly homogenous, or free of "background
noise," a population must be founded by fewer than 100 people, Kruglyak
estimates. Iceland, in contrast, sprung from a migration of more than 10,000
people.
-
- Prior to his arrival last year at the
Hutchinson Center, Kruglyak spent five years as a research scientist in
the laboratory of renowned geneticist Dr. Eric Lander, director of the
Whitehead Institute/Massachusetts Institute of Technology Center for Genome
Research in Cambridge, one of five genetic laboratories participating in
the Chicago-based SNP Consortium.
-
- While at the Whitehead, Kruglyak participated
on the team that in 1995 unveiled the first detailed map of the human genome
- a feat that catapulted the $1 billion, 15-year Human Genome Project ahead
of schedule by at least two years. In late January, Kruglyak became one
of 10 young scientists worldwide to receive a $1 million research fellowship
from the St. Louis-based James S. McDonnell Foundation, established by
the late aerospace research pioneer of the same name. Categories in the
rigorous international competition for the James S. McDonnell Centennial
Fellowship - a one-time grant that honors the 100th anniversary of McDonnell's
birth - ranged from astrophysics and cosmology to human genetics. Kruglyak,
one of two winners in genetics, accepted his award in April in Washington,
D.C.
-
- The Fred Hutchinson Cancer Research Center
is an independent, nonprofit research institution dedicated to the development
and advancement of biomedical technology to eliminate cancer and other
potentially fatal diseases. Recognized internationally for its pioneering
work in bone-marrow transplantation, the Center's four scientific divisions
collaborate to form a unique environment for conducting basic and applied
science. One of 35 National Cancer Institute-designated comprehensive cancer
centers in the nation, it is the only one in the Northwest. For more information,
visit the Center's Web site at <http://www.fhcrc.orghttp://www.fhcrc.org
-
-
- Note: This story has been adapted from
a news release issued by Fred Hutchinson Cancer Research Center for journalists
and other members of the public. If you wish to quote from any part of
this story, please credit Fred Hutchinson Cancer Research Center as the
original source. You may also wish to include the following link in any
citation: <http://www.sciencedaily.com/releases/1999/06/990604080856.htmhttp://www.scien
cedaily.com/releases/1999/06/990604080856.htm
-
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