542
chapter 23
Structure and Properties of DNA
On the other hand, such use of personal medical informa-
tion would generate a society that accepts the concept of
genetic discrimination. Since our society has made great
efforts to eliminate sex, racial, and age-related discrimina-
tion, the overwhelming sentiment is to not allow genetic
discrimination. The question for society is how to guaran-
tee that genetic discrimination will not be practiced either
legally or illegally as more and more DNA information be-
comes part of peoples’ medical records. Laws against ge-
netic discrimination have been introduced in many states
but there is no federal law (as of
2 0 0 0
) that guarantees a
person’s right to genetic privacy.
Drug design:
One of the anticipated benefits of the iden-
tification of human genes involved in diseases is the de-
velopment of highly specific drugs that can be targeted to
correct the biochemical and physiological consequences
of a defective gene and its abnormal protein. It is expected
that drugs eventually can be developed that will be targeted
to correct the effects of specific mutations that individu-
als carry. Drug design and drug therapy may evolve to
the point where each person’s genotype determines the
drug that will be used. Pharmacogenomics is the study
of the relation between human genetic variability in the
activity, toxicity, and metabolism of drugs. Examples in-
clude deficiencies of catabolic enzymes dihydropyrimi-
dine dehydrogenase and thiopurine S-methyl transferase
which can cause profound toxicity to fluoropyrimidine and
mercaptopurine, respectively. These are used in cancer
chemotherapy (Chapter 27).
23.10 Genomics and Proteomics
Enormous progress has been made in recent years in de-
ciphering the genetic basis of different human phenotypes
and clinical diseases that result from inherited mutations.
Technological breakthrough have made the identification
of genes and their sequencing a relatively straightforward
procedure.
Genomics
is the study of DNA and the genes
that it contains. While genomics has resulted in the char-
acterization of many human genes that are responsible for
abnormal phenotypes and genetic disorders, identification
of the protein corresponding to the gene is often difficult
and, in many cases, is still unknown long after the gene
has been identified and sequenced. Often the activity of
the gene does not correlate with the amount of the protein
or its activity in the cell. Posttranslational modifications
cannot be determined by genomics, which only allows
determination of the primary amino acid sequence as de-
duced from the nucleotide sequence of the gene.
Proteomics
is the direct study of proteins produced
by both healthy and diseased cells. For example, two-
dimensional gel electrophoresis can be used to display
and quantify thousands of proteins within a cell. A change
in the level of a particular protein, either higher or lower,
can be detected by differential protein abundance analysis.
When a cell receives a chemical signal, such as the binding
of a growth factor or cytokine, the immediate response is
at the level of proteins that are unrelated to the target gene.
Cell surface receptor proteins are modified in response to
the external signal. Also, transmission of information from
the cell surface to the nucleus is mediated by the physi-
cal movement of proteins. Proteomic technologies have
been developed that can detect and analyze such protein
changes. In addition, the level of a particular protein in the
cell may change dramatically in response to a change in
transcriptional regulation of one or more genes, and this
can be monitored (Chapter 26).
Proteomics is a valuable new technology used in the
development of novel and more effective drugs following
the identification and characterization of disease-causing
proteins. Proteins also provide useful molecular markers
for the diagnosis of specific diseases. In essence, pro-
teomics provides the link between genes, proteins, and
diseases and complements the information obtained by
genomics.
Supplemental Readings and References
Structure of DNA
B. Alberts, A. B. Bray, J. Lewis, et al.:
M o le c u la r B io lo g y o f th e Cell.
New
York: Garland (1994).
S. Henikoff, E. A. Greene, S. Pietrokovski, et at: Gene families: The taxo-
nomy of protein paralogs and chimeras,
S cien ce
278,609 ( I997).
D. W. Ross: The human genome: information content and structure.
H o sp ita l
Practice,
June 15, 49 (1999).
Sequencing DNA
L. Alphey:
D N A S eq u en cin g .
New York: Springer-Verlag (1997).
E R. Blattner, G. Plunkott, C. A. Bloah, et al.: The complete genome se-
quence of
E sch erich ia c o li
K-12.
S c ie n ce
277, 1453 (1997).
F. S. Collins: Sequencing the human genome.
H o sp ita l P ractice,
January
15,35 (1997).
F. S. Collins: Medical and societal consequences of the human genome
project,
N ew E n g la n d Jo u rn a l o f M ed icin e
341, 28 ( 1999).
N. Rosenthal: Fine structure of a gene—DNA sequencing.
N ew E n g la n d
J o u rn a l o f M ed ic in e
332, 589 (1995).
L. Rowen, G. Mahairas, and L. Hood: Sequencing the human genome.
S cien ce
278, 669 (1997).
Properties of DNA
B. H. Hahn: Antibodies to DNA.
N ew E n g la n d J o u rn a l o f M ed icin e
338,
1359(1998).
D. E. Housman: DNA on trial—The molecular basis of DNA fingerprinting.
N ew E n g la n d J o u rn a l o f M ed icin e
332, 534 (1995).
