s Duplicated segments of chromosome
Variation in our chromosomes
A view of all the human chromosomes accord- New work shows that this widespread
ing to the Database of Genomic Variants variation within the human genome is more
reveals that people do not necessarily inherit common than thought and is a legacy of
two copies of every gene. Instead, entire human evolutionary history. Studies are also
sections of a chromosome (shown in blue) beginning to connect copy number variants
spanning thousands to millions of DNA bases with speci c diseases. A few examples:
can be duplicated, deleted or inverted, caus- Variation in copy number of immunity-related
ing the number of copies of genes in those genes on chromosome 17 have been linked
stretches to vary. to susceptibility to HIV/AIDS. Deletions in
chromosome 8 have been linked to schizo-
phrenia (shown) and colonic Crohn’s disease.
A duplication on the same chromosome has
Key
s Reported copy number variants
(Stretches where the chromosome
is duplicated, deleted or inverted.)
s Reported end points between
stretches of inverted sequences
been linked to psoriasis.
X
12
13
14
15
16
17 18
19
20
21
22
Y
ers led by Evan Eichler, a Howard
Hughes Medical Institute investigator at the University of Washington in
Seattle, reported in the Feb. 13 American
Journal of Human Genetics that 1 to
2 percent of people have copy number
variants, or CNVs, that are more than
1 million bases long.
DATABASE OF GENOMIC VARIANTS; INSET: DAVID B. GOLDSTEIN/
DUKE UNIV., MODIFIED FROM PLOS GENETICS, FEBRUARY 2009
“There’s a real CNV burden in the population,” Eichler says.
Culprits in disease
Some of these variations — and perhaps simply the volume of changes — in
the genome may predispose people to
diseases, other studies suggest.
A report published February 6 in the
online journal PLoS Genetics showed
that patients with schizophrenia have
some of the largest variants: chromosome deletions that remove 2 million
or more bases. Such megadeletions
occurred only in eight of the 1,073 schizophrenia patients screened, but in none of
the 2,492 healthy people in the comparison group.
Some big duplications were also
found in people with schizophrenia, but
healthy people had large duplications
too. So researchers think that losses of
large chunks of DNA, not additions, are
more likely linked to schizophrenia.
The international team that conducted the study did not find evidence
linking any of the common SNP variants
previously implicated in schizophrenia
to the disease. The results could mean
that rare, harmful differences are more
important in schizophrenia than are
more common variations. This idea represents a change in thinking about the
genetics of relatively common diseases.
Researchers have thought that common genetic variations might contribute
to common diseases, such as heart disease
and diabetes, when triggered by environmental factors such as poor diet, smoking and lack of exercise. This study’s result
indicates that, at least for schizophrenia,
rare variants that remove different parts
of the genome in different people might
result in the same disease.
Other researchers have demonstrated
that copy number variants, especially
deletions, are important in autism. Last
June, researchers from the University
of Chicago and colleagues, writing in
Biological Psychiatry, reported finding
51 copy number variants—including
duplications as well as deletions — in
46 of the 397 people with autism in the
study. Forty-one people had one variant
and five people had two variants. These
