Significance of the SNP Mapping - Essay Example

THE SIGNIFICANCE OF SNP MAPPING A powerful and emerging genetic tool, the SNP - Single Nucleotide Polymorphism - is expected to revolutionize the field of biomedicine as well as in population studies tracing human history. Biomedical researchers are hopeful of applying SNP information in disease detection as well as in preventative and curative medicine and drug development, as genetic research is today aimed at SNP detection and mapping. The paper attempts to understand the significance of SNP mapping, and its potential benefit to individuals and human society. However, before analyzing the implications and uses of SNP, it would be imperative to understand in clear terms what SNPs are, the nature of their occurrence in human DNA and the development of SNP maps. SNPs and SNP Maps Single Nucleotide Polymorphism or the SNP, as commonly referred to by genetic and biomedical researchers, is a common form of DNA or genetic variation -90% of all variations-that occur within an individual's DNA sequence. [Brookes, 1999, pp: 177] The genetic code is specified by the four-nucleotide "letters" A (adenine), C (cytosine), T (thymine) and G (guanine). SNP variation occurs when a single nucleotide, such as an A, replaces one of the other three-nucleotide letters-C, G, or T. The change or alteration of the DNA segment AAGGTTA to ATGGTTA - the second "A" in the first sequence is replaced with a "T" in the second sequence - is an example of SNP. [NCBI, 2003] SNPs occur about once in every 1,000 bases along the human genome. [Brookes, 1999, pp: 178] The high rate of occurrence of SNPs and their relatively regular distribution, present them as potential genetic markers in studying human genetic variation [Zhao et al, 1998 in Roses, 2000] Though many SNPs have no major effect on cell function, scientists suggest that certain SNPs are indicative of the susceptibility of an individual to diseases as well as the sensitivity or responsiveness to drug. [HGIP, 2004] Otherwise a challenging task, the recent technological advances have enabled scientists to develop techniques to identify and map SNPs by comparing selected regions of a DNA sequence. The SNP map clearly delineates the position at which SNP are located on the human genome sequence. The potential applications of SNP in biomedicine and pharmacology have instigated researchers and scientists to create a high-density SNP map of the human genome that would be available for use by all researchers. It was with this aim that the SNP Consortium (TSC), constituting of world's ten largest pharmaceutical companies, two information-processing companies, the Wellcome Trust and world-leading academic institutions, was launched in April 1999; the project aimed at identifying about 300,000 SNPs, and about half these to be mapped for future use. [Roses, 2000] The project eventually discovered about 1.8 million SNPs. [HGIP, 2004] The U.S. Human Genome Project (HGP) is another team involved in mapping SNPs in human genome. [HGIP, 2004] The Significant Uses of SNP Maps Research suggests that SNP maps present significant potentialities in biomedicine in areas including disease detection; medical diagnostics and individualized prescription of medicines; preventive and curative medicine; development of pharmaceutical products; and in drug surveillance. Variations in DNA sequence such as a SNP occurs in about 1% of the population, [Brookes, 1999, pp: 178] however these genetic variations greatly influence the individual's response to diseases, bacterial and viral infections; response to chemicals and toxins; and also to drugs and other therapies. Apart from its extensive application in biomedical research, because of their genetic stability, SNPs also function as useful genetic or biological markers in population studies. [HGIP, 2004] The SNP maps positively help physicians to identify the multiple genes associated with many complex diseases including cancer, diabetes, vascular disease, and also certain mental illnesses. [HGIP, 2004] These "susceptibility" genes though not causative, contribute significantly to the clinical symptoms of specific diseases. SNP mapping helps in rapid detection of susceptibility genes by narrow can detect small regions of the genome containing a disease susceptibility gene. In a study conducted to determine the usefulness of SNP mapping in identifying a known susceptibility gene for Alzheimer's disease-APO E on chromosome 19, several substantially associated SNP markers were observed around APO E. The study could rapidly identify a small region containing a disease susceptibility gene within the large region of 4 million bases; only two genes were encoded in the region, APO C1 and APO E. [Martin et al, 2000 p. 385-86] SNP maps have also been used to narrow the search of susceptibility genes for migraine and psoriasis. [Cited in Roses, 2000] However SNPs are not absolute indicators of disease development. [HGIP, 2004] Human genes are also understood to influence individuals' responses to a number of medicines; SNP maps helps in faster detection of these genes also. [McCarthy, 2003, p. 136] The Possibilities of SNP Maps The SNP maps are expected to revolutionize medical treatment by aiding individualized medical prescriptions based on predetermined efficacy and safety profile. By comparing the patient's genetic data with SNP maps, physicians can predict the patients who may therapeutically benefit by the clinical trials, and also select those patients who are likely to benefit, for further trials. While the SNP maps may help physicians in reducing the ineffectiveness and risks associated with "trial and error" prescribing, presently employed; [Roses, 2000] it may also help pharmaceutical manufacturers towards developing more effective medicines. [McCarthy, 2003, p. 136] Presently medical prescriptions are based on a patient's symptoms - the phenotype - and the average response of patients to a medicine. [Roses, 2000] SNP mapping technologies enable physicians to correlate the variations in the whole genome with a particular medicine-related phenotype and in developing a brief, yet informative predictive profile, avoiding the need to generate hypotheses for each of the genes involved. Thus SNP maps would help physicians to ascertain the patient's likely response to a disease and/or to a drug, facilitating "personalized prescription" [NCBI, 2003] enabling effectiveness and safety in drug administration; improving efficacy and tolerability of medicines. [Roses, 2000] Drug surveillance, for minimizing the risks due to possibility of adverse events, is another field, where SNP maps offer potential application. Current drug surveillance systems are mostly implemented post-marketing, and are only capable of identifying the adverse events after several hundred thousand patients administer the drug. While the danger involved in present surveillance is momentous, measures such as withdrawal of potential "adverse" drugs from the market also impact patients who would have benefited from the drug without experiencing serious side effects. [Roses, 2000] SNP maps enhance drug surveillance - by comparing the DNA of patients who experienced an adverse effect with the DNA of patients who had no adverse effects, the associated SNPs can be identified. The SNP information helps in effective drug administration, as patients who are susceptible to adverse side effects may be identified beforehand and treated appropriately. [Roses, 2000] Stratifying patients according to genetic variances is also suggested to facilitate drug development and to predict safety or efficacy of drugs, enabling faster approval of new drugs. [McCarthy, 2003, p. 136-7] Implications of SNP Mapping The genetic tests for diseases present many ethical, legal and social issues, which may impact the family and social life of the patient and his or her family. Hence it is important to understand these implications of SNP mapping. While SNP mapping provide information about the susceptibility of an individual to a disease or the likely response to a medicine, it is significant to note that SNP mapping does not test the patient for the presence or absence of a disease gene-specific mutation. SNP mapping technologies available today is not designed to provide any other disease-specific collateral information about the patient or family members. [Roses, 2000] Conclusion Genomics and SNP mapping offer significant benefits to future health care and medical practice. The technology is expected to contribute enormously towards understanding the pathogenesis of disease as well as in drug development; [Robertson, 2003, W41-43] physicians may personalize prescriptions, ensuring greatest benefits and least risks for an individual patient. [Roses, 2000] SNP maps also offer potential application in population studies. Though SNP mapping may be clearly differentiated from other disease gene-specific tests; the genetic based methodology of SNP mapping may be developed to provide disease gene-specific information, which can significantly impact the personal, familial and social life of the patient and his or her family members. Apart from this is the security issue - the unauthorized access and use of the genetic information. Thus genotyping individuals using technologies such as SNP mapping present potential ethical and social issues, [Robertson, 2003, W41-43] which call for appropriate legislation as well as stringent guidelines and policies for the discreet development, use and storage of SNP maps. Bibliography 1. Brookes A. J. 1999. "The essence of SNPs." Gene 234(2): 177-186. Available at: http://brookes.cgb.ki.se/Articles/essence_of_snps_article.pdf Accessed 10/09/05 2. Human Genome Information Project. (HGIP). 2004. "SNP Fact sheet." Available at: http://www.ornl.gov/sci/techresources/Human_Genome/faq/snps.shtml Accessed 10/09/05 3. McCarthy, A. 2003. "Pharmacogenetics: Implications for drug development, patients and society." New Genetics and Society, 19(2): 135-43. 4. Martin E.R., Lai E.H., Gilbert J.R. et al. 2000. "SNPing away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease." American Journal of Human Genetics 67(2): 383-394. 5. National Center for Biotechnology Information (NCBI). 2003. "SNPs: variations on a theme." NCBI's Science Primer. Available at: http://www.ncbi.nlm.nih.gov/About/primer/snps.html Accessed 10/09/05 6. Robertson, J. A. 2003. "The $1000 Genome: Ethical and Legal Issues in Whole Genome Sequencing of Individuals" The American Journal of Bioethics 3(3): W35-W42 7. Roses A.D. 2000. "Increasing Efficacy With Individualized Drugs" Psychiatric Times Vol. XVII (11) Available at: http://www.psychiatrictimes.com/p001152.html Accessed 10/09/05 Read More