The international team of scientists working to determine
the most common variations of the human genome report the
details of their plans, known as the
"HapMap" project, in
the Dec. 18, 2003, issue of Nature.
The team will obtain and identify genetic variations in DNA
samples from 270 people in Nigeria, Japan, China and the
United States. Scientists at Johns Hopkins are one of two
U.S. groups who will analyze the DNA sequences to determine
the most common patterns of genetic variations in
populations. Once finished, the HapMap will provide a
freely available catalog of common patterns, or
haplotypes.
"What we learn from the HapMap project will simplify and
accelerate efforts to identify genes associated with common
chronic diseases," said Aravinda Chakravarti, professor and
director of the
McKusick-Nathans Institute of Genetic
Medicine at Johns Hopkins. "This project is intense
from a DNA analysis perspective, but it's going to make the
next round of studies much easier to do."
The power of haplotypes is that they offer a way of using
the identity of a few key genetic building blocks in a
given region of DNA to infer the rest of the sequence
— possibly tens of thousands of building blocks long.
So instead of having to sequence each person's genome,
future studies could merely identify variants in key
positions (and thus determine a person's haplotype) and
instantly know nearly the entire sequence, the scientists
say.
The Nature article describes the entire HapMap process,
from working with communities to identify participants and
collect samples to choosing which DNA variants to look for
and how to analyze the data to create the actual map. Ten
groups around the world will genotype the samples,
determining which of the four "letters" of DNA's language
are at given positions along the genome.
Ninety samples from the Yoruba people in Ibadan, Nigeria,
will be analyzed, along with 90 from people of northern and
western European ancestry living in Utah. While the
Nigerian and U.S. samples will be from 30 "trios" —
sets of parents and an adult child — 45 samples from
Japanese and 45 samples from Han Chinese will be from
unrelated people.
Chakravarti, who plans to use the freely available products
of the HapMap to determine the genetic underpinnings of
heart disease, diabetes and psychiatric illness, received
funds from the NIH last year to participate in the
international project as one of two computer analysis
centers in the United States. The other analysis group is
at the Center for Genome Research at the Whitehead
Institute in Cambridge, Mass.
"Analyzing the sequence information from all these samples
is going to require new mathematical and computing
methods," Chakravarti said. "So while the sequences and
genotypes are being figured out, we are hard at work
developing new ways to analyze the data so we can be
confident in the map we end up creating. Anything less
isn't enough."
Chakravarti, David Cutler, Carl Kashuk and Peter Chen of
the McKusick-Nathans Institute are co-authors of the
report, along with the many other members of the
International HapMap Consortium. Chakravarti and Hopkins
geneticist David Valle were members of the initial National
Institutes of Health planning group on Populations and
Ethical, Legal and Social Issues. The Johns Hopkins HapMap
effort is funded by the National Institutes of Health.