Polymorphisms genomics

Introduction to Genomics and Single Nucleotide Polymorphisms Genomics... 

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We thank Drs. David Beck and Donald Coppock for helpful discussions and for revising the manuscript. Figures 2A and 4A are reprinted from Robledo, R., Beggs, W., and Bender, P. (2003) A simple and cost-effective method for rapid genotyping of insertion/deletion polymorphisms. Genomics 82,580-582, with permission from Elsevier. This work was supported by funds from the NIGMS Contract NOl-GM-9-2101 and the Coriell Institute for Medical Research. 

Robledo, R., Beggs, W., and Bender, P. (2003) A simple and cost effective method for rapid genotyping of insertion/deletion polymorphisms. Genomics 82, 580-582. 

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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