What Can We Expect from the Human Genome Project?
"Mapping and Sequencing the Human Genome: Science, Ethics, and
Public Policy." Developed by BSCS, in collaboration with the American
Medical Association, under the U.S. Department of Energy Grant
Diagnosis and Prediction of Disorders
Geneticists cloned genes responsible for genetic disorders even before
the organization of the Human Genome Project (HGP). In the last few years, well-publicized
successes included the cloning of genes responsible for Duchenne
muscular dystrophy (DMD), retinoblastoma, cystic fibrosis, and
neurofibromatosis. If other such disease-related genes are isolated,
biologists can learn about the structure of the gene's corresponding
protein and the pathology of the disorder. This knowledge could lead
to better medical management of the resulting disorders.
Several techniques to detect gene mutations allow immediate and
accurate diagnosis in individuals with some symptoms. For example,
before geneticists cloned the DMD gene, the confirmation of a
diagnosis required expensive and uncomfortable tests, and the tests
were inadequate to detect carriers. Now, with only a blood sample,
geneticists can detect most mutations associated with DMD very
rapidly. DNA-based tests clarify the diagnosis quickly and enable
geneticists to detect carriers within the same family.
The probability of erroneous results from a genetic test is small, but
not zero; false-positive or false-negative results can occur because
of technical abnormalities or human error such as the mislabeling of
samples. In addition, some tests such as that for cystic fibrosis
cannot detect all of the mutations associated with the disorder. The
use of genetic tests to detect carriers, for prenatal diagnosis and
for presymptomatic diagnosis, has created ethical and public policy
Genome information can indicate the future likelihood of some
diseases. For example, if the gene responsible for Huntington's
disease is present, it is a near certainty that symptoms eventually
will occur, although geneticists cannot accurately predict the time of
onset. Genome information also helps geneticists predict which
individuals have an increased susceptibility to disorders such as
heart disease, cancer, or diabetes, which result from complex
interactions between genes and the environment. There is no guarantee
that symptoms will occur, but the risk is greater for individuals with
specific genotypes than for the general population.
Insight into Basic Biology
Information generated by the HGP may shed light on several interesting
biological questions. The discovery of new genes is an obvious
benefit, as is the determination of their functions. The organization
of genes within the genome is another area of investigation in
biology. Is it important, for example, for genes to reside on a
particular chromosome, or in a particular order, or both?
When biologists compare the human genome with the genomes of other
organisms, they may gain some insight into molecular evolution,
including human evolution. Comparisons of human and mouse DNA
sequences will help identify genes that are unique to one or more
complex organisms, and comparisons of DNA sequences from humans and
fruit flies or nematodes may help identify genes essential for all
multicellular organisms. Comparisons of human and yeast DNA sequences
may help identify genes related to functions essential for all
Development of New Technologies
The HGP has catalyzed enormous advances in the development of
technology, and it will continue to do so. One of the biggest
challenges of the HGP is finding faster ways to sequence DNA. A yet
unproved idea uses a DNA "chip." The chip is not a piece of
electronic equipment, but an array of short pieces of DNA, each with a
known sequence, arranged on a substrate. When a solution containing
DNA with an unknown sequence is applied to the substrate, some of it
reacts with the short DNA whose sequence is known. The signal
indicates to which unknown sequence the known sequence hybridized.
This yields a pattern that a computer can use to determine the
sequence of bases.
By one estimate, the HGP ultimately will provide 10 million times more
data about each individual than is available at the chromosome level,
and researchers are developing computer hardware and software
necessary to manipulate the huge quantity of data. One important
addition is the Genome Data Base, located in Baltimore, which
incorporates data from human genetic maps as they accumulate. Several
other data bases around the world accumulate sequence data from a
variety of organisms.
Researchers have made great progress in developing automated machines
and robotic work stations to perform repetitive procedures. These
machines are particularly useful in large-scale sequencing operations,
and computers can read the results of a sequencing experiment and load
the data directly into a data base. Although automation accelerates
the procedure and reduces the opportunity for human error, human
involvement is still necessary.
Limits and Opportunities
Determination of the entire DNA sequence contained in the human genome
will not answer the question: What is a human? Geneticists will not
be able to look at a person's DNA sequence and predict everything
about the appearance and characteristics of that person. Even if
geneticists can identify segments of DNA as genes, the vast majority
of the genes they discover still will have unknown functions. In
addition, many human traits such as body stature and intelligence
result from multiple genes, and the exact number of genes that might
contribute to such a trait is not obvious, nor are the ways in which
those genes interact. An individual's genetic make-up greatly
contributes to the type of person he or she is, but environmental
variables such as diet, education, climate, family values, and access
to health care also play a considerable role in determining an
Even in single-gene disorders, there usually is considerable variation
in the expression of the gene. This variability may result from
different mutations in the same gene, environmental effects,
interactions with other genetic features, or any combination of these
factors. Thus, even when geneticists discover a disease-related gene
in an individual, they cannot always predict the exact course of the
Although it may appear that our genes are relatively stable, the human
genome changes continually because of errors in DNA replication.
Genes responsible for genetic disorders may be inherited from one or
both parents, or they may arise from new mutations because of errors
in the replication of an individual's DNA. It is unlikely, therefore,
that a geneticist could absolutely exclude the possibility of a
genetic disorder by examining an individual's genome. New mutations
are more likely in X-linked and autosomal dominant disorders than in
There are certain areas of human genetics in which researchers expect
to expand their current knowledge. Two such areas are the regulation
of gene expression and the role of the vast majority of DNA that has
not yet been assigned a function - the inappropriately named "junk"
DNA. Research published early in 1992 demonstrated that an intron,
which is thought to be a noncoding region of DNA, plays a role in the
function of transfer RNA, which is critical to protein synthesis.
Additional research likely will reveal other functions for such junk
Gqeneticists already have made one surprising observation from their increased knowledge of the human genome - a phenomenon called imprinting. Imprinting describes a molecular signal that indicates whether one allele of a pair was inherited from the mother or the father. Apparently, in some cases it is not sufficient merely to have two copies of a gene. Rather, each copy must be inherited from a different parent.
Imprinting is implicated for example, in Prader-Willi syndrome and
Angelman syndrome. Individuals with either of these disorders are
mentally impaired. Infants with Prader-Willi syndrome usually are
small at birth and may experience respiratory and feeding problems.
They become obese as young children, their skin is sensitive to light,
and their hands and feet are small. Children with Angelman syndrome
have an abnormal puppet-like gait and sudden outbursts of
inappropriate laughter. These two dissimilar disorders apparently
result from a disruption of the same region on chromosome 15, but in
Prader-Willi syndrome, the mutation is inherited from the father,
whereas in Angelman syndrome, the mutation is from the maternal side.
In addition to expanding our knowledge of genetics, the HGP also will provide a number
of new job opportunities in biotechnology, health care, computing and
information storage, and ethics and public policy. Discussions of
ethics and public policy will require input from individuals trained
in disciplines such as philosophy, theology, law medicine, science,
sociology, and public policy.
Go to next story: Whose Genome is It, Anyway?
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