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In test after test, Lee and his colleagues
found that even healthy people have
large gains or losses of DNA. The work
showed 255 stretches in the genome
where at least one of the people tested
was missing DNA or carrying extra,
Lee’s team reported in Nature Genetics
in 2004. The same year another group
independently found 221 places in the
genome where copy number varies. Led
by Michael Wigler of Cold Spring Harbor Laboratory in New York, the group
reported in Science that, on average, any
two people differ at 11 of those places.
The human genome had revealed an
unexpectedly large variability.
“It was a major revelation,” says
Andrew Shelling, a geneticist at the
University of Auckland in New Zealand.
“Certainly when it was brought to our
attention, we were staggered that there
was that much variation.”
The list of variable spots has grown
longer with each attempt to map human
genetic diversity. As of March 11, the
Database of Genomic Variants, hosted
by the Centre for Applied Genomics in
Toronto, listed 6,558 locations in the
human genome where variations may
occur. Some locations have multiple
variations— copy number can vary in
many different ways within one person’s
genome or from one person to another.
The database lists 31 separate studies that document 21,178 copy number
variants of DNA segments 1,000 bases
or longer; 499 inversions (places where a
stretch of DNA is spelled backward); and
16,729 insertions or deletions ranging in
size from 100 bases to 1,000 bases. Many
smaller variations may exist that current
methods can’t easily detect.
Uniquely schizophrenic
Large deletions from chromosome 8 could
be linked to schizophrenia. In one patient,
a portion of the chromosome was almost
entirely missing: The black band shows
the normal width of this region and the red
band shows how much was missing from
this person’s chromosome.
One recent effort to map structural
variability and single letter changes in
2,500 people suggests that 65 to 80 percent of the population has copy number variants that run at least 100,000
bases long. About 5 to 10 percent of
people carry copy number variants
longer than 500,000 bases. Research-
