Branden Tarlow May 28 2002 Biochemistry 118Q Dr Doug Brutlag Final Paper It s not just your genes using genomics to identify trace and treat foreign pathogens With the announcement that the first copy of the human genome has been completed many eyes have turned to the genomic field One bi product of human genome research is the availability of a vast new set of technological tools Because of the human genome project genotype screening techniques have greatly proliferated they are more widely used and widely available for a growing number of researchers and medical professionals In the last decade a combination of new genomic strategies classic molecular fingerprinting techniques of restriction fragment length polymorphism analysis RFLP and epidemiological strategies have helped us better understand disease Elucidating the genetic sequence of individual pathogen strains can help deliver the most efficacious treatment to patients trace diseases in populations in order to design better public health policy and lead to wrongful death convictions In this paper I will discuss these applications in addition to ethical and technical concerns relating to public health and the legal arena where applicable To begin with genotypic identification of pathogen strains allows offers the possibility to better understand the mechanisms of bacteria or viruses Though this technology is not new or novel it has been used in new ways to identify the properties of un culturable bacteria For example by amplifying the DNA with PCR scientists were able to identify and characterize the bacterium associated with Whipple s disease a systemic illness affecting the nervous and gastrointestinal system i In addition genotypic screening has allowed doctors to distinguish between separate diseases with similar phenotypes a growing trend in biology In the 19th century a variety disease that we now may call cancer and heart disease and many others were clumped under the common title consumption which was treated by bloodletting While this now seems absurd the progress in medicine is a macrocosm of how molecular epidemiology will refine the treatment of pathogens A more modern corollary can be found in the discovery of hepatitis Molecular analysis identified patients afflicted with hepatitis to show that hepatitis A B C D and E are separate diseases ii Identifying variation in the genotypes of diseases with similar phenotypes allows medical professionals to better track the spread of disease By knowing what strain of a disease a patient has doctors can prescribe the most efficacious drug to fight that disease This approach is especially useful in treating drug resistant bacterial infections In the worst of infections initially choosing the correct drug that the bacterium is not resistant to instead of operating by trial and error may make a life and death difference Doctors however must ask whether running such an assay is time effective or cost effective Though the host environment is a great variable in disease characteristics understanding of the pathogenesis of the disease can greatly aid treatment Genotype identification is especially applicable in treating human immunodeficiency virus HIV Though it is believed to be an incurable disease the progression of the illness can be treated with a variety of drug cocktails to enhance and lengthen the life of an afflicted person A major problem in administering HIV drugs is that the drug targets constantly change HIV has an extremely high mutation rate due to the inexact nature of the reverse transcriptase enzyme nearly 1 in a 1000 base pairs is incorrectly copied For many years HIV has been treated with protease inhibitors drugs that prevent HIV proteins from being correctly divided and AZT a drug that inhibits reverse transcription and therefore slowing retrovirus action But in its hyper evolution HIV quickly develops drug resistance Consequently to have the most efficacious treatment of the retrovirus it is important to know which drugs the HIV strain is resistant to and which one work the best For example a doctor might enter the RNA sequence of a patient s HIV into the computer and receive an output that says that AZT is only 20 effective on that patient while another drug works is 80 effective Currently databases with this information receive thousands of scan per day from all over the world This technology uses bioinformatics to predict the most likely match based upon alignments in the database iii Because HIV has a great number of nucleotide polymorphisms it is difficult to treat But by the same token the strains take on a personalized aspect that allows epidemiologist to track its evolution For example HIV on the African continent is easily distinguished from that in Europe or Asia Thus by simply looking at a strain and comparing it to a database researchers can roughly identify the source of the virus Even in a smaller cluster of people a high degree of genetic relatedness of HIV strains can suggest common infection sources Several years before the O J Simpson trial genetics molecular biology and epidemiology joined forces to help demonstrate that a dentist infected several of his patients with HIV The dentist who was symptomatic with AIDS continued to practice and five of his patients who had very low risks for HIV infection were found to have the virus Molecular analysis of highly variable regions of the HIV genome were analyzed to show a very significant correlation between the doctor and his patients In the study investigators identified eight signature nonconsecutive nucleotides in a region called C2V3 sequences The theory is that mutations randomly arise in the genetic code in the retrovirus action of HIV Thus when a mutation occurs in one host it is heretically transferred from one HIV molecule to a daughter HIV molecule Thus a newly infected person will receive the same strain of HIV as their host After the moment of infection the genomes will diverge from each other in an essentially random manner this microevolution is influenced by the host s immune system drugs and other variable environmental factors By means of a statistical comparison it was shown that five dental patients shared 7 or more of the signature nucleotides with the dentist while local controls HIV positive people in the same geographic area who didn t have contact with the dentist or the other patients shared 2 or fewer of these markers iv Statistical methods showed this indicated a
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