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http://www.sciencedaily.com/releases/2008/04/
080430134251.htm
Eight New Human Genome Projects Offer Large-scale Picture Of Genetic Difference
ScienceDaily (May 2, 2008) — A nationwide consortium led by the University of
Washington in Seattle has completed the first sequence-based map of structural
variations in the human genome, giving scientists an overall picture of the
large-scale differences in DNA between individuals. The project gives
researchers a guide for further research into these structural differences,
which are believed to play an important role in human health and disease. The
results appear in the May 1 issue of the journal Nature.
The project involved sequencing the genomes of eight people from a diverse set
of ethnic backgrounds: four individuals of African descent, two of Asian
descent, and two of European background. The researchers created what's called
a clone map, taking multiple copies of each of the eight genomes and breaking
them into numerous segments of about 40,000 base pairs, which they then fit
back together based on the human reference genome. They searched for structural
differences that ranged in size from a few thousand to a few million base
pairs. Base pairs are one of the basic units of information on the human genome.
Most previous studies of the genome have focused on small genetic variations
called SNPs (pronounced "snips"), or single-nucleotide polymorphisms -- changes
on the scale of a single base pair. More recent research on the human genome
has shown, however, that larger-scale differences may account for a great deal
of genetic variation among individuals. Structural variation in the human
genome has already been linked to individual differences in susceptibility to
conditions like coronary heart disease, HIV, schizophrenia, autism, and mental
retardation.
In addition to millions of smaller differences, the researchers identified 1695
regions of structural variation in the genome. They also provided a detailed
look at the sequence for 261 regions of the genome, revealing an unprecedented
view of the complexity of the genetic differences among different humans. The
large-scale differences that the researchers were looking for can come in many
forms, such as the deletion of a large swath of DNA, or the insertion of an
out-of-place string of genetic code. Others simply appear as a different number
of copies of a gene or DNA sequence.
Until now, there has not been a comprehensive study to sequence these
variations systematically in multiple individuals. As part of their study, the
authors also discovered 525 segments of DNA that were previously unknown to the
human genetics community.
"There is a perception that the human genome is essentially completely
understood," explained the project's leader, Dr. Evan Eichler, UW associate
professor of genome sciences and an investigator for the Howard Hughes Medical
Institute. "The sequences we have identified range in size from a few thousand
to hundreds of thousands of base pairs, and are not part of the published human
genome reference sequence. We found that many of these are highly variable in
copy and content between individuals. This represents uncharted territory that
can now be examined in more detail to determine the function of these new
segments of the human genome with respect to disease and gene activity."
Eichler expects that the structural variation map will give scientists a much
better picture of genetic variations, and help them better understand these
areas of the genome that are prone to large-scale changes over time. Even more
research is needed on structural variations, the scientists argue in the
article, to help get a more accurate picture of the human genome than what we
already have in the reference genome constructed by the Human Genome Project.
"The important point here is that we could not have found these differences
without sequencing more human genomes from individuals of diverse ancestry to a
high-quality standard," Eichler added.
The project will also serve as a sound resource for the science community, said
Eichler, since the researchers have preserved the many segments of DNA used for
the project. As new genomes are studied, someone might find a new sequence or
new area of variation, and the researchers can revisit that particular segment
of DNA to study it more closely.
In addition to Eichler, several UW researchers in the UW Departments of Genome
Sciences and Medicine worked on the project, including Jeffrey Kidd, a graduate
student in genome sciences, and Maynard Olson, professor of medicine and genome
sciences and director of the UW Genome Center. The project also included
researchers at Agencourt Bioscience Corp. in Beverly, Mass.; Agilent
Technologies in Santa Clara, Calif.; Washington University School of Medicine
in St. Louis; the National Human Genome Research Institute in Bethesda, Md.;
the University of Wisconsin, in Madison; the Broad Institute of MIT and
Harvard, in Cambridge, Mass.; and Illumina, Inc. in San Diego. The researchers
were supported by the National Science Foundation, the Jane Coffin Childs
Memorial Fund, Merck, and the National Human Genome Research Institute, part of
the National Institutes of Health.
Adapted from materials provided by University of Washington, via EurekAlert!, a
service of AAAS.
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University of Washington (2008, May 2). Eight New Human Genome Projects Offer
Large-scale Picture Of Genetic Difference. ScienceDaily. Retrieved February 13,
2009, from http://www.sciencedaily.com /releases/2008/04/080430134251.htm
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