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Second phase of HapMap project is completed
Database of human genetic
diversity allows identification of disease-associated genes
BOSTON - October 17, 2007 - Investigators from six countries
have completed the second phase of the International
HapMap Project, an effort to identify and catalog genetic similarities
and differences among populations around the world. Information
provided in the first phase of the HapMap, completed in 2005, has
led to the development of techniques facilitating the search for
genes associated with common diseases - such as schizophrenia and
heart disease - and the identification of more than 50 such disease-associated
genes.
In the past year, using data and methods based on the HapMap, MGH
researchers have published new genetic contributors to conditions
such as type 2 diabetes, Crohn's disease, elevated blood cholesterol,
rheumatoid arthritis, multiple sclerosis, and prostate cancer. These
studies and many others used a suite of analytical methods developed
at MGH and its partner institutions.
"The original HapMap provided the backbone for genome-wide
association studies that have uncovered previously unsuspected genetic
components of many diseases, leading to new areas of research,"
says Mark Daly, PhD, of the Massachusetts General Hospital (MGH)
Center
for Human Genetic Research, co-senior author of the report in
the Oct. 18 issue of Nature. "The second phase has tripled
the amount of genetic variation assessed and describes up to 95
percent of common single-letter variations in the human genetic
code."
While the Human Genome Project confirmed that the more than 3 billion
"letters" of DNA in each human were 99.9 percent identical,
analyzing the small fraction that differ - including about 10 million
distinct, single-letter variations, also called SNPs - remained
a daunting task. In 2001 Daly and colleagues showed that adjacent
DNA variations are inherited together in segments called haplotypes,
with the boundaries between adjacent segments defined by locations
of enhanced recombination - the shuffling of DNA segments between
the chromosomes inherited from each parent. Based in part on those
findings, the HapMap project was started to create a map of SNPs
and haplotypes across the genomes of 270 individuals from Nigeria,
China, Japan and the U.S. While the first phase identified and cataloged
about 1.3 million SNPs, the second phase has brought the total to
more than 3.1 million SNPs catalogued in the same population.
"The increased density of identified SNPs in the second phase
has allowed us to much more specifically understand the nature of
these recombination 'hotspots.' " says Daly. "Another
interesting finding is that we can identify, among apparently unrelated
individuals, chromosome segments that clearly have been inherited
without change from common ancestors who lived hundreds to a thousand
years ago. The ability to detect these more recently inherited segments
of DNA may hold the key to rare disease-associated variations that
have been hard to detect with current tools." Daly is an assistant
professor of Medicine at Harvard Medical School and a senior associate
member of the Broad
Institute of Harvard and Massachusetts Institute of Technology.
The information in the HapMap is freely accessible to researchers
around the world. The data assembled in the second phase was added
to the public database as it became available and already has been
used in a number of research studies. As the project continues,
it will use new sequencing techniques to further analyze genetic
variations in the same study group and in a larger population.
"While the completion of Phase 2 of the HapMap Project makes
possible comprehensive studies of common SNPs in the sampled populations,
there remains much work to be done," says David Altshuler,
of the MGH Center for Human Genetic Research. "Current efforts
aim to catalogue genetic variation in more diverse samples from
around the world, to define larger chromosomal alterations that
might be missed by SNPs-based approaches, and to find rare genetic
variations that might have potent effects on individual patients.
Only by combining all these approaches can we hope to have a complete
understanding of the genetic root causes of common human diseases."
Altshuler is also an associate professor of Genetics and Medicine
at HMS, director of the Program in Medical and Population Genetics
at the Broad Institute, and co-chair for Analysis of the International
HapMap Project.
The HapMap project is supported by a broad range of agencies - both
governmental and private - in the participating countries, and includes
investigators from more than 70 research, education, biotechnology
and other scientific organizations.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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