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| Identifying and Using SNPs |
In order to identify SNPs, nucleotide sequences of two or more genomic regions must be aligned so that the polymorphisms are apparent. Sequence alignments are easy when the sequences are similar, but can be very difficult when there are many polymorphisms. The alignment of two sequences is determined by a program that compares the two sequences, nucleotide by nucleotide. For multiple sequences, the program continues the same type of pairwise alignment for all possible pairs. The result is a pairwise distance matrix based on all possible alignments of any two sequences. This matrix is then used to construct a phylogenetic tree that predicts how closely related two sequences are, based on their similarity. The program then uses this information to align the sequences, again in order of their relatedness. This is the method used in a program called CLUSTAL. A typical output from CLUSTAL is shown in Figure 5.
Most SNPs have no effect on an individual, so what use are having maps of them? SNPs appear to cluster in blocks called haplotypes. Grouping individuals that share a particular haplotype is called haplotyping. Because these particular sequences of SNPs on a chromosome are inherited together as blocks, they can be used to distinguish individuals and populations. What good is haplotyping? One can determine what specific diseases or other traits are associated with different haplotypes. In most cases, there are much fewer haplotypes than SNPs. Although it is the SNPs that actually cause disease, looking for changes in one SNP out of millions in the genome is not practical; looking for a particular haplotype is much easier.
An example of the value of haplotype comes from research on Crohn's disease. Crohn's disease is a chronic inflammatory disease of the digestive tract that tends to cluster in families. Researchers identified a haplotype on chromosome 5 that correlates with the disease. This region of the chromosome contains genes involved in immunity; these genes then may be important in other inflammatory diseases, such as lupus or asthma.