934
UNIT SIX
mation. Researchers can now test existing drugs and develop
new ones against these new targets.
In the coming years, as the human genome continues to
be analyzed, detailed portraits of the living chemistry within
our cells, and the chemical crosstalk among cells, will con-
tinue to be painted of the human body. It is a new view of
anatomy and physiology.
PRACTICE
23
State the three types of molecules that gene expression proF
ling
describes.
24
Explain how gene expression proF
ling provides information
about physiology.
25
Discuss how gene expression proF
ling can be helpful in medical
practice.
and how quickly the disease will progress; indicate which
drugs are likely to be effective and which will likely produce
intolerable side effects; and monitor response to treatment.
Tests based on gene expression proF
ling enable physicians
to prescribe the antidepressant or cholesterol-lowering drug
most effective for a particular patient—a more personalized
approach to medicine than trying one drug at a time, based
on the fact that it is effective in some people.
The power of gene expression proF
ling in normal anat-
omy and physiology, as well as in pathology, comes from
comparing sets of mRNAs. A muscle cell from a person with
diabetes mellitus expresses different genes (makes different
proteins) than a muscle cell from a person whose glucose
metabolism lies within the normal range. These differences
are expected. Analyzing gene expression can also
discover
new aspects of physiology. This was the case for spinal cord
injury. Comparing gene expression proF
les in cerebrospinal
fl uid from individuals who had suffered spinal cord injury
to those of individuals who had not been injured revealed
activation of the same set of genes in the spinal cord injury
patients whose protein products heal injury to the dermis.
Looking at the protein profiles in the fluid added to our
knowledge of tissue repair.
Gene expression proF
ling is perhaps most valuable in
anatomy and physiology when it enables medical research-
ers to see distinctions that their eyes cannot detect. Clinical
Application 14.2 (p. 536) describe a subtype of leukemia
lumped in with a different type for many years, because the
cancerous white blood cells looked alike. On a biochemical
level however, the cells were different. Once gene expres-
sion proF
ling revealed the distinctions, affected children
were given different treatments, and survival increased
(f
g. 24.15)
.
Identifying proteins produced in abnormal or injured
cells also suggests new drug targets. Consider rheumatoid
arthritis (RA), an autoimmune disorder that causes great
pain and deformity to joints (see the opening photo to chap-
ter 8, p. 260). Researchers prepared DNA microarrays from
cells in joint fluid from pairs of monozygous (identical)
twins in which one had RA and the other didn’t, indicating
that it is not inherited. The affected twins had high levels of
three types of mRNA. The encoded proteins made sense: one
destroys bone and cartilage; one deactivates the hormone
cortisol, whose levels are diminished in RA; and the other
stimulates blood vessel formation, which enhances infl
am-
FIGURE 24.15
DNA microarrays reveal a “hidden” type of leukemia.
It is easy to see that these three leukemias—ALL, MLL, and AML—di±
er
in their gene expression patterns. The vertical columns of squares
represent tumor samples, and the horizontal rows compare the
activities of particular genes. Red tones indicate higher-than-normal
expression and blue tones show lower-than-normal expression. The
di±
erent patterns indicate very distinct cancers, although the cells may
look alike . Once children with MLL were correctly diagnosed, they
were given more e±
ective treatments.
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