Detection of Common Cytokine and Colony Stimulating Factor Gene Polymorphisms

With the completion of the first map of the entire human genome, it is estimated that there are approx 35,000 genes, which encode for translated RNA and protein products (1 ,2 ). The difference between any two human genomes is estimated to be less than 0.1% (3 -5 ). However, in light of the magnitude of the genome (approx 3.2 billion bases), the number of variations is still very large (6 ). The most common variation is the single-nucleotide polymorphism (SNP), which, by definition, has a frequency of greater than 1%. Therefore, it is possible that the number of SNPs in a given individual could number in the millions (6 ). Variable nucleotide repeats (useful for microsatellite studies), deletions, and substitutions are rarer in frequency, but still useful tools for genetic analysis (e.g., linkage studies and whole-genome scans). SNPs occur at an interval of approximately once every 1.3 kb of DNA (3 ,7 -9 ). In the investigation of polymorphisms, particular emphasis is directed not only at the coding region, but also at 5? and 3? regulatory regions of the candidate genes, such as the promoter which plays an important part in controlling gene transcription. The 3? -untranslated region (3? UTR) can determine RNA half-life or ribosomal translation of RNA species. Nonsynonymous SNPs (viz. those that change the coding amino acid) constitute less than 5% of SNPs in coding regions. Variations in introns or exons are probably less frequent than variations in intergenic regions (8 ,9 ).