538
chapter 23
Structure and Properties of DNA
P r o te a s i
n u c le o p ro te in
in c y to s o l
T r a n s c n p tio n
a p p a r a tu s
E n d o p la s m ic
re tic u lu m
C D 8
c le a v e s viral
v ira l n u c le o p ro te in
cytotoxic
T cell
Plasmid DNA Vector
T ra n s la tio n
V iral
r e c e p to r
p ro m o te r
n u c le o p ro te in
g e n e
mRNA
Golgi
i n,i k i;
23-16
How a DNA vaccine might work. A viral gene coding for a core or capsid protein is inserted into a plasmid. The
plasmids are injected into cells where the plasmid migrates to the nucleus. Viral proteins are expressed in the cells
producing both a cell-mediated and humoral immune response. (Reproduced with permission from W. M. McDonnel
and F. K. Ashari, DNA vaccines,
N. E ngl. J. M ed.
3 1 4 ,44 (1996)].
although the level of such antibodies is not always predic-
tive of the severity of the disease. Genetic susceptibility
also seems to play a role in the pathogenicity of DNA
antibodies in some individuals.
Antibodies
to
double-stranded
DNA
may
cause
glomerulonephritis by forming antibody-DNA complexes
that become trapped in the glomeruli. In some cases, DNA
antibodies can be recovered from damaged tissues in pa-
tients with SLE or glomerulonephritis, indicating that the
antibodies are involved in tissue damage. The produc-
tion of DNA antibodies is reduced by immunosuppressive
drugs, and immunosuppressive therapy is the accepted
treatment for SLE and related diseases caused by anti-
bodies directed against DNA.
23.9 The Human Genome Project
A complete human genome, the total genetic information
in a haploid set of chromosomes, contains approximately
3.1 billion bases and 50,000-1000,000 genes that encode
proteins. The Human Genome Project was established
with federal funds to obtain the complete sequence of a
human genome or, more accurately, the sequence of pooled
DNA extracted from cells donated by several anonymous
individuals. Initially a public research effort, the sequenc-
ing task later was undertaken by a private company, Celera
Genomics (Rockville, MD). The ensuing competition led
to a joint announcement by the U.S. Government and Cel-
era Genomics on June 26, 2000 that the human genome
had essentially been sequenced although there were still
gaps and errors in the sequence. The two groups agreed to
continue cooperating to complete the sequence of a generic
human genome as soon as possible.
Any two human genomes are approximately 99.9%
identical in sequence. Of course, the 0.1% represents a
difference of 3 million bases between any two individuals,
and these base differences may have profound effects on
disease susceptibility, behavior, intelligence, personality,
and other traits. Approximately 75% of all human genes
have the same DNA sequence in all individuals except for
those with rare mutations.
The type of genetic markers employed in the dissection
of the human genome include
