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Genetic Testing
By Felix Roudier
Summer Discovery Program: Exploring Careers in Medicine
Instructor: Steve Anisman
Summer, 1998



History of Genetics
      In 1865, Mendel was the first person to talk about inhereditary characteristics. In his experiments with pea plants he noticed certain traits were passed on to later generations of plants, sometimes "skipping" a generation. His research laid the groundwork for genetic science, and is known today as "Mendelian Genetics".
      In the early 1900's, Morgan discovered the existence of chromosomes, using fruit flies, opening the genetics field to development.
      In 1953, Crick and Watson uncovered the structure of DNA, which is shaped like a double helix.
      In 1966, Nirenberg "cracked" the genetic code, finding its structure: a DNA strand is made of a string of amino acids, each made of a combination of three nucleotide bases.
      Scientists still make progress, and the biggest genetic project of the moment is the mapping of the Human Genome, which should increase the power of genetic testing.
Chromosome:
      A chromosome is a tiny structure composed of Nucleic Acids and Proteins, found in all animal and plant cells. It contains the Deoxyribonucleic Acid, which contains genes. Human cells have 23 pairs of chromosomes
Gene:
      A gene is a unit of inheritance, a region of the deoxyribonucleic acid that determines a certain characteristic of a plant or animal. Genes are carried by chromosomes and are arranged in a line along each chromosome. Since a DNA molecule is made of a string of nucleotide bases, each gene is actually a string of nucleotide bases, aligned in a certain order. Each gene codes for a specific protein, by producing RNA.
What is genetic testing? How does it work?
      Genetic testing, basically, consists in screening a persons genes, in search for the presence of a certain gene, or visible genetic disorders. Cloning one of a persons genes and comparing it to a "normal" gene allows scientists to determine if or not the person has a genetic disorder. Genetic testing has been possible since scientists began to clone genes. Not all of the human genome has been cloned yet, and many genes remain unknown. The complete mapping of the human genome (human genome project) is expected to be done by 2003. At that time, scientists will be able to test a person's entire genome for disorders. Today however, not all disorders are known. Today genetic testing can be used to determine if or not a patient is predisposed to be victim of a certain disease; searching for a genetic disorder in a persons genes will tell if the person has a high risk of developing that disease. These tests could be applied to any disease whose genetic sequence is known. Two genes in particular, BRCA1 and BRCA2 are known to predispose for breast and ovarian cancer. Screening for these two genes allow doctors to determine how high a risk the person endures of developing cancer.
How does it work?
      In the past years, and still today, scientists would amplify certain regions of a gene, in order to identify them. In order to do so, they use different techniques: PCR for amplification, and blots to read gene expression. These techniques work well, but have limits, regarding the cost of screening a whole gene, regarding the time it might take to do so, and regarding to the special skill needed to proceed.
PCR:
      In 1983, Kary Mullis invented the Polymerase Chain Reaction (PCR), a technique by which a small fragment of DNA can be multiplied many times. PCR mimics the DNA duplication process that occurs in our cells. During duplication, the two strands that make up DNA separate, and an enzyme, polymerase (An enzyme that catalyzes the synthesis of nucleic), copies each strand. The process requires a supply of Nucleotide bases, which are the four "basic building blocs" of DNA, Thymidine, Cytosine, Guanine, and Adenosine, and a fragment of the DNA strand, called a primer, which helps start the duplication. In the first phase of the reaction, the original DNA is heated, causing the individual strands to separate. Second, the temperature of the mixture is lowered, allowing the primer to bind to the separated DNA. In the third phase, the temperature is raised again, to a level at which the polymerase can copy the DNA molecule rapidly. These phases, all carried out in the same container, make up one complete PCR cycle, taking less than two minutes to complete. PCR is used today in research, and has a wide variety of applications. It enables scientists to create genetic sequences in quantities large enough to study. Because only tiny amounts of DNA are required, PCR is used for research in biology, clinical medicine… In biological research, PCR has accelerated the study of gene function and genetic mapping. In forensic science, PCR is used for the DNA fingerprinting that identifies or excludes a suspect using small amounts of human tissue left at a crime scene… For his discovery, Mullis received the Nobel Prize for Chemistry in 1993.
Blots
      PCR allows scientists to gain amounts of genetic sequences large enough to study. To read and understand these sequences, they use blots, which allow them to search for specific fragments of DNA, RNA, and specific proteins. The southern blot is a technique used for searching specific DNA fragments. You separate DNA fragments by gel electrophoresis. That means you pass an electrical current through a mixture of similar molecules (in this case DNA). Each molecule travels through the medium at a different rate. Separation is based on these differences. Agarose and acrylmide gels are the most frequently used for electrophoresis. This allows you to separate different parts of molecules and visualize them. After probing the gel with the complementary strand of the DNA region you are looking for, complementary strands should have hybridized (they should have bound together). The Northern and Western Blots are similar techniques, but they are used to identify portions of RNA strands and proteins.
      Considering the amount of data the human genome withholds, and the speed at which it will all be sequenced, the use of such slow techniques seems impossible; testing one persons genes would be too long, and too expensive.
      That's why scientists are developing new ways of testing genes rapidly, and cheaper than traditional techniques. One of these new techniques is "Chip Technology". The way the chip works is based on the idea that a strand of DNA will stretch to a complimentary strand:
A    T
T    A
G    C
G    C
G    C
      Each chip is an exact complimentary strand of a "healthy" gene. When laced with the sequenced gene of a patient, if both strands are complementary, as they should be if the patient's gene has no mutation, they will interact. If they don't interact properly, it means the patients strand has a disorder.
      By "copying" "healthy" genes onto chips and comparing them to patients' sequenced genes, using this technique, scientists save time and money. These are important considerations in genetic testing, because of the overwhelming quantity of genes in the human genome.
Every day applications of genetic testing
      Some genes are known to predispose people to certain diseases. In the case of genes BRCA1 and BRCA2, the disease is breast and ovarian cancer. These genes are known to increase a person's risk of developing those types of cancer.
      Testing a person who has a strong family history of breast or ovarian cancer helps determine if or not the person has a high risk of developing cancer too. If so, the person could be followed closely by a doctor, preventing the disease from spreading out of control. Early diagnosis could be done through genetic testing. It could also reassure people by making sure they don't have that gene.
      Testing a person's genes also helps determine if a form of cancer is hereditary or random, thus reassuring the rest of the family. Many other diseases are known to be hereditary. Alzheimer Disease is found to be very hereditary. Three mutation sites have been identified. Testing for mutations on the presenilin1 and presenilin2 genes, and on the amyloid protein helps predict Alzheimer Disease.
Consequences of genetic testing
      Genetic testing enables doctors to diagnose certain diseases early in their development, or warn the patients about their condition, thus preventing it from going unknown for years. The patient can be treated immediately, and people who family members can also see if they share the same risks. From this point of view, genetic testing appears to be a very good science. However, there are drawbacks to testing.
      The swiftness at which the human genome is being sequenced will allow scientists to identify which genes and mutated genes cause a predisposition to which disease. But with no known cure for many of these genetic diseases, that information will be useless, sometimes even harmful; imagine being told you were going to have Alzheimer Disease, and knowing there is no known cure for it, or finding out you have a high risk of developing cancer. This information would greatly effect an individual's life, keeping him probably from doing things he would have thought about doing, scaring him about his future.
      Genetic testing can also hurt people through the information it reveals to others; a person known to be predisposed to cancer because she has the BRCA1 or BRCA2 gene, will have trouble finding insurance. Which insurance company would grant the same rates to a person who has high risks of needing a lot of medical care later on in her life, and a person found to be genetically perfect?
      Protecting the patients is the most important thing. If employers had access to a database of genetic information concerning their employees, which might happen one day, people with even slight genetic disorders would be penalized.
      Genetic testing offers a wide variety of information that would make people's lives better, like providing information about genetic diseases. But the danger of providing such precise information about a person must be seen in this progress: someone could choose how they want their employees to be, or make "perfect" people, thus abusing of the power given to them through other people's research.

Bibliography

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