Genomic Polymorphisms

Locus Gene/s/ Gene symbol Size of region Frequency of polymorphism Associated phenotype References 

4pl6 Multiple genes Multiple genes 6 Mb 12.5% inversion None known 23 

2 Survival of motor neuron 1, 2 SMN1 Entire genes 4% dup Spinal muscular atrophy 47 and 48 

3 Cytochrome P450 CYP21A2 CYP21A2 32.7 or 26.4 kb 1.6% dup Congenital adrenal hyperplasia 49 

8p23 Multiple genes Multiple genes 2.5-5.3 Mb 26% inversion Panic disorder 51 

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Stiiber, F Petersen, M., Bokelmann, F., and Schade, U A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-a concentrations and outcome of patients with severe sepsis. Crit. Care Med. 24,381-384 (1996). 

Hayward-Lester A, Chilton BS, Underhil PA, Oefher PJ, Doris PA. 1997. Quantitation of spedfic nudeic adds, regulated RNA processing and genomic polymorphism using reversed-phase HPLC. Gene quantification. Ferre F, editor. Boston Birkhauser. 

Stoehlmacher J, Park DJ, Zhang W et al. A multivariate analysis of genomic polymorphisms prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal... 

Baba T, Bae T, Schneewind O, Takeuchi F, Hiramatsu K (2008) Genome sequence of Staphylococcus aureus strain Newman and comparative analysis of staphylococcal genomes polymorphism and evolution of two major pathogenicity islands. J Bacteriol 190 300-310 Bannerman TL, Kloos WE (1991) Staphylococcus capitis subsp. ureolyticus subsp. nov. from human skin. Int J Syst Bacteriol 41 144-147... 

Dunlap PV, Jiemjit A, Ast JC, Pearce MM, Marques RR, Lavilla-Pitogo CR. Genomic polymorphism in symbiotic populations of Photobacterium leiognathi. Environ Microbiol 2004 6 145-58. 

Riva, A. A., and I. S. Kohane. 2001. A web-based tool to retrieve human genome polymorphisms from public databases. Proc AMIA Symp 558-62. 

Big pharmaceutical companies have begun to seek another path. Their objective is to find a gene or haplotype through genome polymorphism or SNP mapping and then identify its connection to a disease and so ascertain the susceptibility of the patient. The idea is that a molecule will bind the encoded protein selectively to block its action, thereby putting a halt to its adverse effects, in theory at least. 

Benghiat FS, Charbonnier LM, Vokaer B, De Wilde V, Le Moine A (2009) Interleukin 17-producing T helper cells in alloimmunity. Transplant Rev (Orlando) 23 11-18 Bernal W, Donaldson P, Underhill J, Wendon J, Williams R (1998) Tumor necrosis factor genomic polymorphism and outcome of acetaminophen (paracetamol)-induced acute liver failure. 

Pastinen, T., Ge, B., and Hudson, T. J., Influence of human genome polymorphism on gene expression. 

Polymorphisms in the human genome are often not independently transmitted i.e., a polymorphism is associated with particular variants present on the same chromosome. Recombination erodes this association, but for physically close polymorphisms (e.g., within a gene), the correlation, known as LD, persists over time. 

CYP2J2 is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that possess potent anti-inflammatory, vaso-dilatory, and fibrinolytic properties. Polymorphic alleles with reduced function are known. Some other CYP2 subfamilies and isozymes listed in Table 1 are still not well characterized, in part because most of them were discovered in the course of the human genome project. 

Essential to the definition of Pharmacogenetics is the term genetic polymorphism. It is extrapolated that there are at least three million genetic polymorphisms in the human genome. Historically, a genetic polymorphism was defined as a genetic variation with a population frequency of 1% and above, but the larger inter-ethnic variation of population frequencies makes a strict definition based on such frequencies impractical. The most common molecular type of polymorphism is the... 

Single Nucleotide Polymorphisms (SNPs) are single base pair positions in genomic DNA at which normal individuals in a given population show different sequence alternatives (alleles) with the least frequent allele having an abundance of 1% or greater. SNPs occur once every 100-300 bases and are hence the most common genetic variations. 

There is a normal variation of DNA sequence just as is true of more obvious aspects of human structute. Variations of DNA sequence, polymorphisms, occur approximately once in evety 500 nucleotides, or about 10 times per genome. There are without doubt deletions and insertions of DNA as well as single-base substitutions. In healthy people, these alterations obviously occur in noncoding regions of DNA or at sites that cause no change in function of the encoded protein. This heritable polymorphism of DNA structure can be associated with certain diseases within a large kindred and can be used to search for the specific gene involved, as is illustrated below. It can also be used in a variety of applications in forensic medicine. 

SNP Single nucleotide polymorphism. Refers to the fact that single nucleotide genetic variation in genome sequence exists at discrete loci throughout the chromosomes. Measurement of allelic SNP differences is useful for gene mapping studies. 

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