A SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence

Abstract

The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR-RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]

Figure 1

(following page) Distribution of polymorphisms on human chromosome 22. An ideogram of chromosome 22 with a schematic representation of the Giemsa banding pattern is shown at left. Next, the region containing the finished sequence is expanded to show the SNP map. The SNP density (the number of candidate variants in consecutive 100-kb regions) is plotted (blue line) superimposed on a plot of GC density (green). GC content is calculated as a percentage of the sequence using a sliding 100-kb window moved in 50-kb increments. The first column to the right of the graph represents sequences color-coded as per the collaborating institutions that contributed to the sequence pale yellow bars drawn horizontally across the map represent current gaps in the completed sequence. The next column to the right (Var. Density) shows a gray scale coding the number of potential variations recorded in the given 100-kb region. Such potential variations may be SNP, insertion, or deletion polymorphisms relative to the published reference sequence. The next column represents these variations as line annotations with color coding to represent the position of the variation relative to genomic features such as exons and CpG islands (a color key is on the diagram). The last column represents the corresponding map of recently published TSC (The SNP Consortium) SNPs reported by our group. The very high density of the overlap variations described in this paper (the Variations column) is not evident from the diagram because of the limits of the resolution. This diagram can also be viewed as a link from http://www.sanger.ac.uk/cgi-bin/humace/snp_search where a zoom facility allows regions to be enlarged to show the positions of individual SNPs relative to annotated exons and CpG islands.