FAQ
Q. What are the potential benefits of human genome research?
The project will reap fantastic benefits for humankind, some that we can anticipate and others that will surprise us. Generations of biologists and researchers will be provided with detailed DNA information that will be key to understanding the structure, organization, and function of DNA in chromosomes. Genome maps of other organisms will provide the basis for comparative studies that are often critical to understanding more complex biological systems. Information generated and technologies developed will revolutionize future biological explorations.
Q. What is gene testing? How does it work?
Gene tests (also called DNA-based tests), the newest and most sophisticated of the techniques used to test for genetic disorders, involve direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic examination of stained or fluorescent chromosomes. In gene tests, scientists scan a patient's DNA sample for mutated sequences. A DNA sample can be obtained from any tissue, including blood. For some types of gene tests, researchers design short pieces of DNA called probes, whose sequences are complementary to the mutated sequences. These probes will seek their complement among the three billion base pairs of an individual's genome. If the mutated sequence is present in the patient's genome, the probe will bind to it and flag the mutation. Another type of DNA testing involves comparing the sequence of DNA bases in a patient's gene to a normal version of the gene.
Q. Does behavior have a biological basis? Are our actions and emotions related to our genetic makeup?
Behavior often is species specific. A chickadee, for example, carries one sunflower seed at a time from a feeder to a nearby branch, secures the seed to the branch between its feet, pecks it open, eats the contents, and repeats the process. Finches, in contrast, stay at the feeder for long periods, opening large numbers of seeds with their thick beaks. Some mating behaviors also are species specfic. Prairie chickens, native to the upper Midwest, conduct an elaborate mating ritual, a sort of line dance for birds, with spread wings and synchronized group movements. Some behaviors are so characteristic that biologists use them to help differentiate between closely related species.
Behaviors often breed true, that is, we can reproduce them in successive generations of organisms. Consider the instinctive retrieval behavior of a yellow Labrador or the herding posture of a border collie. Behaviors change in response to alterations in biological structures or processes. For example, a brain injury can turn a polite, mild-mannered person into a foul-mouthed, aggressive boor, and we routinely modify the behavioral manifestations of mental illnesses with drugs that alter brain chemistry. More recently, geneticists have created or extinguished specific mouse behaviors-ranging from nurturing of pups to continuous circling in a strain called "twirler"- by inserting or disabling specific genes.
In humans, some behaviors run in families. For example, there is a clear familial aggregation of mental illness.
Behavior has an evolutionary history, as demonstrated by the persistence of some behaviors across related species. Chimpanzees are our closest relatives, separated from us by a mere 2 percent difference in DNA sequence. We and they share behaviors that are characteristic of highly social primates, including nurturing, cooperation, altruism, and even some facial expressions. Genes are evolutionary glue, binding all of life in a single history that dates back some 3.5 billion years. Conserved behaviors are part of that history, which is written in the language of nature's universal information molecule:DNA.
So you see, there is a biological basis to personality and behaviour, but not completely.
Q. How can you be identified by your DNA? What are other applications for DNA forensics? If we are 99% alike, won't two people likely have the same DNA makeup?
Any type of organism can be identified by examination of DNA sequences unique to that species. Identifying individuals within a species is less precise at this time, although when DNA sequencing technologies progress farther, direct comparison of very large DNA segments, and possibly even whole genomes, will become feasible and practical and will allow precise individual identification.
To identify individuals, forensic scientists scan about 10 DNA regions that vary from person to person and use the data to create a DNA profile of that individual (sometimes called a DNA fingerprint). There is an extremely small chance that another person has the same DNA profile for a particular set of regions.
DNA identification can be quite effective if used intelligently. That means that those portions of the DNA sequence that vary the most between humans must be used; also, large enough portions must be used to overcome the fact that human mating is not absolutely random.
Consider the scenario of an crime scene investigation...
Assume that type O blood is found at the crime scene. Type O occurs in about 45 % of Americans. If investigators only type for ABO, then finding that the "suspect" in a crime is type O really doesn't tell you very much.
If, in addition to being type O, the suspect is a blond, and blond hair is found at the crime scene, then you now have two bits of evidence to suggest that your suspect really did it. However, there are a lot of Type O blonds out there.
If you find that the crime scene has footprints from a pair of Nike Air Jordans (with a distinctive tread design) and the suspect, in addition to being type O and blond, is also wearing Air Jordans with the same tread design, then you are much closer to linking the suspect with the crime scene.
In this way, by accumulating bits of linking evidence in a chain, where each bit by itself isn't very strong but the set of all of them together is very strong, you can argue that your suspect really is the right person.
With DNA, the same kind of thinking is used; you can look for matches (based on sequence, or on numbers of small repeating units of DNA sequence) at a number of different locations on the person's genome; one or two (even three) isn't enough to be confident that the suspect is the right one, but 4 (sometimes 5) are used and a match at all 5 is rare enough that you (or a prosecutor or a jury) can be very confident ("beyond a reasonable doubt") that the right person is accused.
Only one-tenth of a single percent of DNA (about 3 million bases) differs from one person to the next. Scientists can use these variable regions to generate a DNA profile of an individual, using samples from blood, bone, hair, and other body tissues and products.
In criminal cases, this generally involves obtaining samples from crime-scene evidence and a suspect, extracting the DNA, and analyzing it for the presence of a set of specific DNA regions (markers).
Scientists find the markers in a DNA sample by designing small pieces of DNA (probes) that will each seek out and bind to a complementary DNA sequence in the sample. A series of probes bound to a DNA sample creates a distinctive pattern for an individual. Forensic scientists compare these DNA profiles to determine whether the suspect's sample matches the evidence sample. A marker by itself usually is not unique to an individual; if, however, two DNA samples are alike at four or five regions, odds are great that the samples are from the same person.
If the sample profiles don't match, the person did not contribute the DNA at the crime scene.
Q. Is gene therapy being used to cure diseases? What is its promise for the future of medicine?
Gene therapy is very young and experimental. Many factors have prevented researchers from developing successful gene therapy techniques.
The first hurdle is the gene delivery tool. How is a new gene inserted into the body? This is done via vehicles called vectors (gene carriers), which deliver therapeutic genes to the patients' cells. Currently, the most common vectors are viruses. Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of the virus's biology and manipulate its genome to remove the disease-causing genes and insert therapeutic genes. Viruses, while effective, introduce other problems to the body --toxicity, immune and inflammatory responses, and gene control and targeting issues. Some alternatives to viruses that have been considered are complexes of DNA with lipids and proteins.
Researchers are also experimenting with introducing a 47th (artificial human) chromosome to the body. It would exist autonomously along side the standard 46 chromosomes --not affecting their workings or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and it is anticipated that, because of its construction and antonomy, the body's immune systems would not attack it --producing the negative responses described for viruses in the previous paragraph.
For more info on how gene therapy has affected people, go to this news article: http://www.nationalpost.com/content/features/genome/0314005.html
Q. Why is model organism research important? How closely related are mice and humans? Why do we care what diseases mice get?
Mice and humans (indeed, most or all mammals including dogs, cats, rabbits, monkeys, and apes) have roughly the same number of nucleotides in their genomes -- about 3 billion base pairs. This comparable DNA content implies that all mammals contain more or less the same number of genes, and indeed our work and the work of many others have provided evidence to confirm that notion.
Similarities between mouse and human genes range from about 70% to 90%, with an average of 85% similarity but a lot of variation from gene to gene (e.g., some mouse and human gene products are almost identical, while others are nearly unrecognizable as close relatives). Some nucleotide changes are "neutral" and do not yield a significantly altered protein. Others, but probably only a relatively small percentage, would introduce changes that could substantially alter what the protein does.
Put these alterations in the context of known inherited human diseases: a single nucleotide change can lead to inheritance of sickle cell disease, cystic fibrosis, or breast cancer. A single nucleotide difference can alter protein function in such a way that it causes a terrible tissue malfunction. Single nucleotide changes have been linked to hereditary differences in height, brain development, facial structure, pigmentation, and many other striking morphological differences; due to single nucleotide changes, hands can develop structures that look like toes instead of fingers, and a mouse's tail can disappear completely. Single-nucleotide changes in the same genes but in different positions in the coding sequence might do nothing harmful at all. Evolutionary changes are the same as these sequence differences that are linked to person-to-person variation: many of the average 15% nucleotide changes that distinguish humans and mouse genes are neutral; some lead to subtle changes, whereas others are associated with dramatic differences. Add them all together, and they can make quite an impact, as evidenced by the huge range of metabolic, morphological, and behavioral differences we see among organisms.
What are knockout mice?
Knockout mice are transgenic mice whose genetic code has been altered by the insertion of foreign genetic material into their DNA. Using this technology, researchers target specific genes --causing them to be expressed or inactivated. These mice are then bred --creating a population of offspring with the trait.
Knockout mice have many benefits. They not only allow researchers to determine gene function and understand diseases at the molecular level, but they also aid scientists in testing new drugs and devising novel therapies.
Why are mice used in this research?
Mice are genetically very similar to humans. They also reproduce rapidly, have short life spans, are inexpensive and easy to handle, and can be genetically manipulated at the molecular level.
Q. When is a genome completely sequenced?
In December 1999, the 56-Mb sequence of human chromosome 22 was declared essentially complete, yet only 33.5 Mb were sequenced. In early spring of this year, the fruit fly Drosophila's 180-Mb genome also was announced as completed, although just 120 Mb were characterized. What's the deal?
Animal genomes have large DNA regions that currently cannot be cloned or assembled. In the human genome sequence, these regions include telomeres and centromeres (chromosome tips and centers), as well as many chromosomal areas packed with other types of sequence repeats.
Most unsequenceable areas contain heterochromatic DNA, which has few genes and many repeated regions that are difficult to maintain as clones for DNA sequencing. HGP scientists strive to sequence the entire euchromatic DNA, which generally is defined as gene-rich areas (including both exons and introns) that are translated into RNA during gene expression. In the case of human chromosome 22, the sequenced 60% represents 97% of euchromatic DNA. Similarly, nearly all the euchromatic regions were sequenced for Drosophila.
So basically, there is much difficulty defining when a genome has been fully mapped out.
Q. What is jumping DNA?
Nearly half of the human genome is composed of transposable elements or jumping DNA. First recognized in the 1940s by Dr. Barbara McClintock in studies of peculiar inheritance patterns found in the colors of Indian corn, jumping DNA refers to the idea that some stretches of DNA are unstable and "transposable," ie., they can move around-on and between chromosomes.
This theory was confirmed in the 1980s when scientists observed jumping DNA in other genomes. Now scientists believe transposons may be linked to some genetic disorders such as hemophilia, leukemia, and breast cancer. They also believe that transposons may have played critical roles in human evolution.