SNP & HGP
Human Genome Project SNP Mapping Goals
In 1998, as part of their latest five-year plan, the DOE and NIH Human Genome Programs established goals to identify and map SNPs. These goals are as follows:
| Develop technologies for rapid, large-scale
identification and scoring of single-nucleotide polymorphisms and other DNA
sequence variants.
| Identify common variants in the coding
regions of most identified genes.
| Create a SNP map of at least 100,000 markers.
| Develop the intellectual foundations for
studies of sequence variation.
| Create public resources of DNA samples and
cell lines. | |
There has been much discussion of late about the utility of SNPs for genetic mapping, but it is important to take a balanced look at benefits and challenges of these genetic markers. Much of the SNP focus has been centered around potential technologies for assaying this class of genetic marker, which promises simple “yes/no” tests that can be performed in a parallel fashion. Many promising new technologies are on the horizon, but it will take time to develop them into products that can reliably deliver a steady and usable data stream. However, technology issues aside, the genetics of SNP markers should be considered to determine how they will fit into the arsenal of genetic tools.
SNPs are generally biallelic systems, that is, there are two alleles that an individual may have for any particular marker. This means that the information content per SNP marker is relatively low when compared to microsatellite markers, which may have upwards of 10 alleles. It has been estimated that it will take approximately 5 SNP markers to equal the information of one microsatellite marker, meaning that ~2,000 SNPs will be required to equal a 10 cM microsatellite map. And informative microsatellites can potentially have the benefit of rare alleles associated with traits of interest; if one of an SNPs two alleles is relatively rare, then it will not be an informative marker in most cases (most individuals will share the same genotype).
SNPs also tend to be very population-specific; a marker that is polymorphic in one population may not be very polymorphic in another. This means that polymorphic SNP markers will have to be generated specifically targeted to the population under study, which means a great deal of resequencing to generate good markers. By comparison, microsatellite markers have been shown to be polymorphic across populations, which means that once generated they can be used universally.
SNP markers offer a number of benefits that will make them an increasingly valuable tool in the genetic arsenal. SNPs, found approximately every kilobase, offer the potential for generating very high density genetic maps, which will be extremely useful for developing haplotyping systems for genes or regions of interest. And because of the nature of SNPs, they may in fact be the polymorphisms associated with the disease phenotypes under study. The low mutation rate of SNPs also makes them excellent markers for studying complex genetic traits. In how to utilize the benefits of mapping complex traits, one should think in terms of SNPs and microsatellites, and how to integrate the use of these valuable genetic markers. The challenge going forward will be on how to best integrate and make use of both types of genetic markers to develop the richest and most versatile genetic maps for unraveling the puzzles of complex genetic diseases.