“This changes the way we think about the
inheritance of disease.” — JOSEPH NADEAU
Ghost of ancestor’s genes lingers
By Laura Sanders
Great-grandfathers may impart more
than engraved watches. A sugar-regulat-ing gene that made a brief appearance
in a lineage of mice but wasn’t passed on
seems to have made animals resistant to
obesity up to four generations later.
“This changes the way we think
about the inheritance of disease,” study
coauthor Joseph Nadeau of the Institute
for Systems Biology in Seattle said March
30. The results may force researchers to
grapple with complicated transgenera-tional gene influences.
The surprising effect may be caused
by the single-generation appearance of
a genetic variation that affects the maintenance of blood sugar. Nadeau and
colleagues allowed two inbred strains of
mice to eat as many of the mouse equivalent of double cheeseburgers as they
Mice on a rich diet became fat (right) or
thin depending on an ancestor’s genes.
wanted. One type of mouse grew obese
and developed health problems such as
insulin resistance, high blood pressure
and cardiovascular disease. The other
type didn’t gain weight, even though
these mice ate more and exercised less.
When the part of the skinny mouse’s
DNA containing the blood sugar gene was
inserted into the obesity-prone mouse,
the mice stayed slim on the high-fat diet.
But here the story gets strange: Even if
the piece of DNA swapped into a mouse
was not passed on to descendants, the
effect was still evident generations later.
The original mouse’s great-grandchildren
remained slender, even on a high-fat diet.
Though these mice didn’t inherit the
actual gene, they did inherit some ghostly
imprint of it. “The reason they are the way
they are isn’t in them,” Nadeau said. “It
was in the previous generation.”
The findings are “breathtaking,” says
computational biologist Sorin Istrail
of Brown University. The results might
help resolve a genetics mystery: Some
traits — including obesity — are strongly
inherited. But so far, researchers have
been able to identify genes that explain
just a tiny part of this total heritability. A
gene from generations earlier that left a
biochemical mark might explain some of
the “missing” effect, Istrail said.
New mutations
evolve in cancer
Acute myeloid leukemia data
may aid choice of treatment
By Laura Sanders
As a man’s cells grew cancerous, a wide
range of mutations emerged too, a new
genetic study finds. The results provide
a deep understanding of the genetic
changes that allowed an aggressive form
of leukemia to take hold in one patient.
“Cancer’s origins lie in the genome,”
Elaine Mardis of Washington University
in St. Louis said March 28. “These genetic
approaches are really addressing the
underlying questions of cancer biology.”
In the new study, Mardis and colleagues
collected cells from a 65-year-old man
with myelodysplastic syndrome, a blood
disease. About one in four people with
this disorder develop a rapidly progressing cancer called acute myeloid leukemia.
Two years after those samples were taken,
the man was diagnosed with full-blown
acute myeloid leukemia, and the researchers harvested a second batch of cells. By
reading the cells’ DNA sequences letter
by letter, the team pinpointed genetic
changes as the cells turned cancerous.
Over time, the cells accumulated new
genetic mutations. Early mutations didn’t
run rampant and overtake all the cancerous cells but didn’t disappear, either. Early
mutations became present in less and less
of the cancer-cell population.
Watching the same cancer in the same
person over time allows the team to see
just how this cancer evolves, says computational biologist Cenk Sahinalp of
Simon Fraser University in Canada.
The finding helps answer a long-stand-
ing question: In leukemia, does a group of
cells with a particular mutation rapidly
spread, or do additional mutations pop up
along the way and result in a cancer that’s
more genetically mixed? In colon cancer,
for instance, most cells in the final tumors
contain the same mutations as the early
mutations, suggesting that they spread
quickly. Yet in this patient, for this partic-
ular leukemia, more mutations occurred.
