Reading Bits of Genetic Information: Methods for Single-Nucleotide Polymorphism Analysis
- Ulf Landegren1,3,
- Mats Nilsson1, and
- Pui-Yan Kwok2
- 1Department of Genetics and Pathology, Uppsala University, Se-751 23 Uppsala, Sweden; 2Division of Dermatology, Washington University, School of Medicine, St. Louis, Missouri 63110 USA
This extract was created in the absence of an abstract.
Information about the genome of our species is accumulating along two dimensions: While the latitudes of our chromosomes are being charted, crudely at first, but with the expectation of a complete nucleotide sequence of one reference human genome early next millennium, the longitudes of sequence variation at specific locations in the genome are also explored, revealing how different we all are. This variation consists mostly of sequence differences in single nucleotide positions, referred to as single nucleotide polymorphisms or SNPs. An expanding panel of known sequence variants, along with greatly improved methods to monitor them, now promise to offer fresh insights into human biology and pathophysiology. We will discuss some of the advantages of these markers as a background for a presentation of high-throughput techniques to analyze them with an outlook toward the future of such techniques.
Extremely efficient methods will be required for analysis of large numbers of sequence variants in many patient samples to identify subtle genetic risk factors that go undetected in current genome scans by use of fewer markers and limited sample sizes. Moreover, as more and more genetic factors of known relevance for diseases are being identified, extensive panels of disease-associated markers are likely to be routinely applied to secure diagnoses of patients. SNPs are expected to take the place of simple tandem repeat polymorphisms—microsatellites—as markers in disease gene mapping, just as the microsatellite markers rapidly replaced the restriction fragment-length polymorphism markers. There are four main reasons for the increasing popularity of SNPs as markers in genetic analysis. (1) They are far more prevalent in the genome than microsatellites, furnishing large sets of markers near or in any locus of interest. (2) Some of the SNPs located in genes can be expected to directly affect protein structure or expression levels, and these may, therefore, represent …
